J Patrick
Loyola University Chicagocity: Maywood country: United States (us)
Grant 5U10CA046282-24 from National Cancer Institute
Abstract: This application is being submitted by Loyola University Chicago, Stritch School of Medicine, Cardinal Bernardin Cancer Center for renewal of this institution´s long-standing participation as a site for the conduct of clinical trials under the umbrella of the Southwest Oncology Group (SWOG). Loyola remains a highly productive member of SWOG, enrolling 674 subjects to SWOG studies over the past 5 year grant cycle. Twenty-one members of the Division of Hematology/Oncology faculty are members of SWOG. Loyola´s Departments of Radiation Oncology, Surgery, Thoracic Surgery, Urology, Gynecology and Pathology are active participants in SWOG-sponsored studies, identifying patients for inclusion in SWOG studies and for the subsequent treatment of these patients. The Clinical Research Office of the Cancer Center consists of 11 Registered Nurses, 4 Protocol Coordinators and 1 Regulatory Data Coordinator, who coordinate approximately 150 total clinical trials for all of the above disciplines. Loyola has four affiliate institutions participation in SWOG studies Good Samaritan Hospital in Downers Grove, Illinois; Central DuPage Hospital in Winfield, Illinois, Edward Hospital in Naperville, Illinois, and Quad Cities CGOP in Davenport, lowa. Plans are underway to increase our commitment to SWOG during the next grant cycle both by increasing accruals with additional planned affiliates and increasing our scientific participation. RELEVANCE The Southwest Oncology Group is one of the NCI´s CTEP-supported cooperative groups which seek new and more effective therapies for cancer. PRINCIPAL INVESTIGATOR Dr. Stiff is an experienced clinical researcher with a long-term commitment to SWOG programs. He is fully qualified for his role on this application. PROTECTION OF HUMAN SUBJECTS (Resume) ACCEPTABLE No concerns are evident. INCLUSION OF WOMEN PLAN (Resume) ACCEPTABLE Women account for 63% of all enrollments. No concerns are evident. INCLUSION OF MINORITIES PLAN (Resume) ACCEPTABLE Minority accrual could be improved. Hispanics represent 10% of accruals and African-Americans represent only 3% of accruals. They report a series of important efforts to increase accrual of minority populations including development of a position for a community outreach coordinator, the work of a physician liaison to the Hispanic community, the use of short form consents for non-English speakers, the use of patient navigators, the provision of low cost screening breast studies for the medically underserved, and offering studies to a broad geography across the Chicago area. Additional planning efforts to increase minority accrual are needed. INCLUSION OF CHILDREN PLAN (Resume) ACCEPTABLE Enrolled subjects are generally 18 years of age or older. OVERALL RECOMMENDATION This application is rated 24 and is recommended for six years of support
Keywords: 0-11 years old; 18 year old; Accounting; African American; Afro American; Afroamerican; Area; black American; Black or African American; Black Populations; Breast; Cancer Center; Cancer Therapy Evaluation Program; Cancer, Oncology; Cancers; chest surgery; Chicago; Child; Child Youth; children; Children (0-21); Cities; Clinical; clinical investigation; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Community Outreach; Conduct Clinical Trials; Consent Documents; Consent Forms; cost; CTEP; Data; Development; Discipline; effective therapy; eighteen year old; enroll; Enrollment; experience; Faculty; Geography; Grant; Gynecology; Hematology; hispanic community; Hispanic Populations; Hispanics; Hispanics or Latinos; HOSP; Hospitals; human subject protection; Human, Child; Illinois; improved; Informed Consent Documents; Informed Consent Forms; Institution; interest; Investigators; Latino Population; malignancy; Malignant Neoplasms; Malignant Tumor; medical schools; medically underserved; member; Minority; neoplasm/cancer; oncology; Operation; Operative Procedures; Operative Surgical Procedures; Participant; Pathology; Patients; Physicians; Population; Position; Positioning Attribute; Principal Investigator; programs; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; Qualifying; R.N.; Radiation Oncology; Recommendation; Registered nurse; Reporting; Research Personnel; Researchers; Role; screening; Screening procedure; screenings; Series; Site; social role; Southwest Oncology Group; Spanish Origin; surgery; Surgical; Surgical Interventions; Surgical Procedure; SWOG; Thoracic Surgery; Thoracic Surgical Procedures; Universities; Urology; Woman; Work; youngster
Project start date: 1988-01-01
Project end date: 2015-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
5U10CA046282-24 (2011): $338795
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to J Patrick
MULTIPLEX NANOCARRIER-BASED HYDROGELS FOR PREVENTION OF VAGINAL HIV TRANSMISSION.
J Patrick, Parke-davis Chair Professor
Rutgers The St Univ Of Nj New Brunswickcity: New Brunswick country: United States (us)
Grant 5R01AI084137-03 from National Institute Of Allergy And Infectious Diseases
Abstract: With the incidence of HIV infection on the rise, the development of vaccines and topical microbicides has been a major worldwide priority. However, the results of recent trials have been disappointing. As such, the induction of sterilizing immunity and protection against HIV infection continues to be a major public health goal. ´Microbicides´, topically applied agents that prevent HIV transmission from person to person, are still believed to hold considerable promise. In fact, it has been suggested that a microbicide with only 60% efficacy could prevent about 1 million HIV infections per year. Given recent clinical failures, there is an urgent need to rethink the concept of microbicides. Therefore, the long-term objective of the proposed research is to design, construct and evaluate a multiplex nanocarrier-based polyethylene glycol (PEG) vaginal hydrogel for preventing HIV transmission. PEG is nontoxic and biocompatible. Hydrogels resemble living tissue due to their high-water content and soft/rubbery characteristics. The hydrogel is a liquid upon instillation allowing for high vaginal dispersion/mucosal coverage where it then undergoes a rapid phase transition to form a visco-elastic gel. The proposed gel must be multifunctional since it has been shown that (1) sexually transmitted and genital infections such as bacterial vaginosis (BV) increase the risk of HIV transmission by weakening mucosal barriers and by stimulating an inflammatory response that may activate or recruit HIV target cells to the portals of viral entry, (2) low vaginal pH (<4.5) is essential for the prevention of vaginal infections but is not sufficient to inhibit vaginal pathogens and to prevent infection, and (3) cell-associated HIV breaches the normal vagina stratified squamous epithelial barrier but with low frequency. The gel matrix will be formed by crosslinking various PEG nanocarriers each of which plays a unique role in the functional properties of the hydrogel (e.g., promoting mucosal adhesion, maintaining mildly acidic pH, releasing microbicide and spermicides, and preventing HIV virion binding). We will design, synthesize, characterize, and evaluate a series of crosslinking nanocarriers that impart a variety of functional properties to the microbicide hydrogel. Aim 1 To construct an effective physical viral barrier using a fast forming, degradable hydrogel with high vaginal dispersion, high mechanical strength, and viscoelastic properties. Aim 2 To create nanocarriers possessing acidifying agents using natural acids and/or the microbicide/spermicide subtilosin. Aim 3 To fabricate polyanionic or RGD nanocarriers to prevent free or cell-associated HIV binding. Aim 4 To evaluate the various crosslinking nanocarriers and hydrogels in cell, tissue and animal models. If successful, the proposed research will result in a novel multifunctional hydrogel technology that possesses the ideal properties of an anti-HIV microbicide it will be colorless, odorless, inexpensive to manufacture, safe to use more than once a day and for long periods of time, fast-acting, undetectable to either partner, and available in contraceptive and noncontraceptive forms. With the incidence of HIV infection on the rise, the development of vaccines and topical microbicides has been a major worldwide priority but the results of recent trials have been disappointing. ´Microbicides´, topically applied agents that prevent HIV transmission from person to person, are still believed to hold considerable promise. The proposed research seeks to design, construct and evaluate an instantly-forming multifunctional vaginal hydrogel to prevent the initial infection and dissemination of HIV through the vaginal mucosa to distant tissues in the body
Keywords: Acids; Adhesions; Animal Model; anti-HIV microbicide; Bacterial Vaginosis; base; Binding (Molecular Function); Biocompatible; Cell model; Cells; Characteristics; Clinical; Contraceptive Agents; crosslink; design; design and construction; Distant; Epithelial; Failure (biologic function); Frequencies (time pattern); Gel; genital infection; Goals; HIV; HIV Infections; Hydrogels; Immunity; Incidence; Infection; Infection prevention; Inflammatory Response; Life; Liquid substance; Local Microbicides; Mechanics; microbicide; Mucous Membrane; nanocarrier; novel; pathogen; Persons; Phase Transition; Play; Polyethylene Glycols; prevent; Prevention; Property; public health medicine (field); Recruitment Activity; Research; Risk; Role; Series; Spermatocidal Agents; Technology; Time; Tissue Model; Tissues; Topical application; transmission process; vaccine development; Vagina; Viral; Virion; Water
Relevance: NARRATIVE With the incidence of HIV infection on the rise, the development of vaccines and topical microbicides has been a major worldwide priority but the results of recent trials have been disappointing. ´Microbicides´, topically applied agents that prevent HIV transmission from person to person, are still believed to hold considerable promise. The proposed research seeks to design, construct and evaluate an instantly-forming multifunctional vaginal hydrogel to prevent the initial infection and dissemination of HIV through the vaginal mucosa to distant tissues in the body
Project start date: 2009-09-15
Project end date: 2013-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: RFA-AI-08-007
5R01AI084137-03 (2011): $378564
INFLUENCE OF WHITE MATTER DAMAGE ON STEP INITIATION
J Patrick, Associate Professor
University Of Pittsburgh At Pittsburghcity: Pittsburgh country: United States (us)
Grant 5R01AG031118-04 from National Institute On Aging
Abstract: While the influence of peripheral motor and sensory function on mobility is well known, a relatively unexplored area is how subclinical central nervous system dysfunction in older adults affects mobility. Damage to frontal-subcortical (F-SC) white matter tracts, identified as white matter hyperintensities (WMH) on MRI, has been identified as one of the factors associated with mobility impairments in older adults. These pathways are an integral component of F-SC circuits that modulate motor output for postural tasks. The primary F-SC circuit associated with motor control is the skeletomotor circuit, which is responsible for selection and initiation of movement, and encoding of direction, velocity and duration of movement. Another F-SC circuit that may affect mobility and balance function is the dorsolateral-prefrontal circuit, which plays a major role in executive function processes, including selective attention. Importantly, elements of executive function are recognized for their role in balance control, especially in older adults. The goal of this research is to investigate the relationship between damage to F-SC white matter tracts and mobility dysfunction in more detail. Community-ambulating older adults aged 70-85 years across a wide spectrum of mobility impairment will be tested. The damage to white matter tracts will be quantified by applying automated algorithms to compute the volume of white matter hyperintensities and fractional anisotropy in specific fiber tracts important for motor control. Mobility impairment will be assessed using both experimental and clinical measures. The experimental protocols will use choice reaction step tasks to assess the function of the skeletomotor and dorsolateral-prefrontal F-SC circuits. The choice reaction step tasks require subjects to step as quickly as possible to one of two potential step locations based on a salient visual cue under conditions with and without executive function involvement. The primary response measure from these tests is the amount of time to initiate the step. To complement the experimental tests, subjects will undergo a clinical balance assessment that uses tests of varying complexity (e.g. Short Physical Performance Battery, Multiple Tasks Test). In addition, clinical tests of executive function will be performed. Multiple linear regression models will be used to relate the measures of tract-specific white matter damage to the experimental and clinical measures, while controlling for confounding variables such as age medication use, and peripheral sensory function. stural dysequilibrium in older adults can markedly affect function and quality of life and increases the risk of injury and death due to falls. The contribution of subclinical central nervous system disease to balance dysfunction and falls is less understood. This research will help to identify a potential pathologic cause (i.e. damage to white matter) that contributes to age-related mobility impairment, and help to identify an area that should be a target of future interventions for improving mobility in older adults
Keywords: Affect; Age; age related; aged; Algorithms; Anisotropy; Area; base; Central Nervous System Diseases; Cessation of life; Clinical; Communities; Complement; Confounding Factors (Epidemiology); Cues; Elderly; Elements; Equilibrium; executive function; falls; Fiber; foot; Functional disorder; Future; Goals; Health; imaging modality; Impairment; improved; improving mobility; Injury; Intervention; Lateral; Left; Leg; Limb structure; Linear Regressions; Location; Magnetic Resonance Imaging; Measures; Modeling; Monitor; Motor; motor control; Motor output; Movement; Neuraxis; Neuropsychological Tests; Pathologic; Pathway interactions; Performance; Peripheral; Pharmaceutical Preparations; Play; Process; Protocols documentation; Quality of life; Reaction; Research; response; Right-On; Risk; Role; selective attention; Sensory; Side; Specificity; Testing; Time; Visual; white matter; white matter damage
Relevance: Postural dysequilibrium in older adults can markedly affect function and quality of life and increases the risk of injury and death due to falls. The contribution of subclinical central nervous system disease to balance dysfunction and falls is less understood. This research will help to identify a potential pathologic cause (i.e. damage to white matter) that contributes to age-related mobility impairment, and help to identify an area that should be a target of future interventions for improving mobility in older adults
Project start date: 2008-09-30
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-07-070
5R01AG031118-04 (2011): $294655
HOUSING INSTABILITY IN CHILD WELFARE-INVOLVED FAMILIES: IMPACT ON EMOTIONAL, BEH
J Patrick
De Paul Universitycity: Chicago country: United States (us)
Grant 5R03HD066066-02 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: This study proposes to conduct secondary data analyses of the National Survey of Children and Adolescent Well-Being (NSCAW), a nationally representative longitudinal study of families investigated for child abuse and neglect. The aim of this project is to inform service provision targeted at families in contact with child welfare services primarily due to the inability to secure safe and affordable housing. Findings will inform the development of an R01 proposal to use a natural randomized-controlled trial to test the effects of housing voucher provision compared to services-as-usual. The present study intends to test the hypothesis that housing instability disrupts the development of emotional, behavioral, and academic outcomes in children. Analyses will, first, examine within-individual changes on housing instability and associated growth in developmental outcomes over time. By explicitly modeling housing changes, analyses directly estimate the effects of moving into and out of housing stability on developmental growth trajectories. Analyses also propose to examine whether child developmental problems are mitigated or prevented when caregivers receive housing vouchers (formerly known as Section 8). If housing instability predicts outcomes, then the receipt of assistance to find and pay for housing should relate to better outcomes. In the absence of experimental data, this study proposes to use propensity score matching (PSM) procedures to minimize selection bias and test the effects of housing vouchers on child welfare-involved families. The aim of this project is to inform service provision targeted at families in contact with child welfare services due to the inability to secure safe and affordable housing. Findings will inform the understanding of risk for housing instability and the development of housing interventions
Keywords: Accounting; Address; Adolescent; Behavioral; Build-it; Caregivers; Child; Child Abuse and Neglect; Child Development; Child Welfare; Complex; Data; Data Analyses; Development; Ecology; effective intervention; Effectiveness; Emotional; Face; Family; Family Study; foster care; Future; General Population; Growth; Homelessness; Housing; housing instability; Individual; Intervention; intervention effect; Left; Life; Longitudinal Studies; member; Modeling; Movement; National Institute of Child Health and Human Development; Nature; NIH Program Announcements; Outcome; Personal Satisfaction; Policies; Population; Poverty; Prevalence; prevent; Preventive Intervention; Probability Samples; Problem behavior; Procedures; Process; public health relevance; Randomized Controlled Trials; Recommendation; Research; Research Design; Research Personnel; Risk; Role; Sampling; Science; Secure; Selection Bias; Services; Shelter facility; Social Policies; supported housing; Surveys; System; Testing; Time; voucher; Work
Relevance: Narrative The aim of this project is to inform service provision targeted at families in contact with child welfare services due to the inability to secure safe and affordable housing. Findings will inform the understanding of risk for housing instability and the development of housing interventions
Project start date: 2010-07-02
Project end date: 2012-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-08-068
5R03HD066066-02 (2011): $69360
HOUSING SERVICES FOR CHILD WELFARE FAMILIES: IMPACT ON STABILITY AND WELL-BEING.
J Patrick
De Paul Universitycity: Chicago country: United States (us)
Grant 1R01HD067540-01A1 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: This study aims to evaluate the effectiveness of a housing intervention for inadequately housed families under investigation by the child welfare system, as well as to understand the mechanisms and conditions through which the program most benefits child development. The intervention - the Family Unification Program (FUP) - is a Housing and Urban Development (HUD) initiative that provides Housing Choice Vouchers (Section 8) to families whose inadequate housing risks out-of-home placement. The study proposes to take advantage of a natural experiment that will randomly provide FUP services to intact families (n = 192) who will be compared to a child welfare services-as-usual control group (n = 192). Oversampling will occur in both conditions to account for voucher uptake failure and attrition. The study will obtain two baseline assessments before housing services and then re-assess at 6-, 12-, and 24-months post-baseline for a total of five time points. Caregivers and their children will be administered a panel survey. Administrative data from multiple services systems linked at the individual- and family-level will be integrated to allow comparisons to the population of child welfare-involved families in Chicago (n = 700). Administrative data sources include child welfare, public housing, Medicaid, public schools, and cash assistance. The study will test a number of hypotheses 1) it is hypothesized that families receiving housing services will report greater family stability - as indicated by residential stability, housing quality, daily routines, noise and confusion, caregiver mental health, caregiver separations, and school changes - compared to child welfare services-as-usual; 2) it is predicated that the housing intervention will have a significant positive impact on child physical and mental health, academic achievement, and developmentally adaptive behavior, relative to services-as-usual; 3) we hypothesize that positive effects on child development associated with housing services will function through reductions in family instability; 4) we hypothesize that families from less cohesive and more violent neighborhoods will gain less from the intervention; 5) we hypothesize that the housing intervention will have its greatest impact on families who are most unstable at baseline; 6) it is theorized that the housing intervention will have greater positive effects for younger children. The rigorous design enables strong scientific investigation of how FUP functions and whether intervention operates similarly across multiple levels of context. This project intends to improve understanding of the mechanisms of the FUP intervention to provide a stronger basis to build evidence-based service models and public policy. This study takes advantage of a natural experiment to test the effectiveness of an intervention for inadequately housed families under investigation for child maltreatment. The proposed study simultaneously aims to inform social policy and service provision in the child welfare system, while investigating the processes involved in the relationship between family instability and adverse child development among at-risk families
Keywords: Academic achievement; Accounting; Adaptive Behaviors; Address; Age; base; Caregivers; Chicago; Child; Child Abuse and Neglect; Child Development; Child Welfare; Confusion; Control Groups; Costs and Benefits; Data; Data Sources; design; Development; Ecology; Effectiveness; Effectiveness of Interventions; Environment; evidence base; expectation; Failure (biologic function); Family; Goals; Home environment; Housing; housing instability; improved; Individual; Intervention; intervention effect; intervention program; Investigation; Link; maltreatment; Mediating; Medicaid; Mental Health; Modeling; National Institute of Child Health and Human Development; Natural experiment; Neighborhoods; NIH Program Announcements; Noise; novel; Outcome; Pattern; Perception; Personal Satisfaction; physical conditioning; Play; Population; Process; programs; public health relevance; Public Housing; Public Policy; Recommendation; Relative (related person); Reporting; Research; Research Personnel; Residential Mobility; Risk; Role; Safety; Schools; Science; Secure; Services; Social Policies; Social work (field); Surveys; System; Testing; theories; Time; U.S. Department of Housing and Urban Development; uptake; Violence; voucher
Relevance: This study takes advantage of a natural experiment to test the effectiveness of an intervention for inadequately housed families under investigation for child maltreatment. The proposed study simultaneously aims to inform social policy and service provision in the child welfare system, while investigating the processes involved in the relationship between family instability and adverse child development among at-risk families
Project start date: 2011-04-01
Project end date: 2016-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-08-069
1R01HD067540-01A1 (2011): $388680
GENE EXPRESSION DURING SPORULATION
J Patrick
Temple Universitycity: Philadelphia country: United States (us)
Grant 5R01GM043577-23 from National Institute Of General Medical Sciences
Abstract: This proposal focuses on how spores are formed by Bacillus subtilis. B. subtilis has become a paradigm for the study of spore formation, and of cell differentiation in prokaryotes, because of the ease of its genetic manipulation. All the key regulators of B. subtilis spore formation are also found in other spore forming species including the pathogens B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile, the causes of anthrax, tetanus, gas gangrene, botulism and colitis following antibiotic therapy, respectively. The highly resistant spores are critical to the survival of theses species in nature. Conclusions from a study of B. subtilis will have general validity for these species. Spore formation involves a characteristic division into two different cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature spore. Spore formation requires the action of four RNA polymerase factors, ?F and then ?G in the prespore and ?E and then ?K in the mother cell. It presents a fundamental problem of developmental biology how is gene expression coordinated with morphological change? The proposal addresses this problem. When the ?F-directed signal from the prespore to activate ?E in the mother cell is delayed, a novel developmental path is taken, in which two spores are formed within one mother cell. This behavior opens up the proposed study of how chromosome replication and growth are controlled during sporulation. It facilitates a study of how genetically identical organisms in the same population can follow different developmental paths. Translocation of the chromosome into the prespore follows activation of ?F. It is proposed to study how completion of translocation leads to engulfment of the prespore by the mother cell and activation of ?G in the engulfed prespore. This proposal focuses on the fundamental problem of how gene expression is coordinated with morphological changes during formation of spores by Bacillus subtilis. All the key sporulation regulatory genes are also found in related pathogens, including B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile. Emphasis is placed on how altering the timing of signaling can change the developmental path taken
Keywords: Address; Affect; anthracis; Anthrax; Anthrax disease; Antibiotic Therapy; Antibiotic Treatment; B. anthracis; Bacillus anthracis; Bacillus subtilis; Behavior; biological signal transduction; botulinum; Botulism; C. difficile; C. perfringens; C. welchii; C.difficile; Cell Communication and Signaling; Cell Differentiation; Cell Differentiation process; cell growth; Cell Signaling; cell type; Cells; Cellular Expansion; Cellular Growth; Characteristics; Chromosomal dislocation; Chromosomal translocation; chromosome dislocation; chromosome replication; chromosome translocation; clostridial tetanus; Clostridium difficile; Clostridium perfringens; Clostridium tetani; Clostridium welchii; Colitis; Development; Developmental Biology; DNA biosynthesis; DNA Replication; DNA Synthesis; DNA-Dependent RNA Polymerases; DNA-Directed RNA Polymerase; EC 2.7.7.6; Event; experiment; experimental research; experimental study; Gas Gangrene; Gene Expression; Generalized Growth; Genes, Regulator; Genetic; genetic manipulation; Growth; Health; Image Analyses; Image Analysis; image evaluation; in vivo; Intracellular Communication and Signaling; living system; Mothers; Nature; novel; Nucleoside-triphosphate[{..}]RNA nucleotidyltransferase (DNA-directed); ontogeny; Organism; pathogen; pathway; Pathway interactions; Population; Prokaryotae; prokaryote; Prokaryotic Cells; Regulator Genes; regulatory gene; Reproduction spores; research study; Resistance; resistant; RNA Polymerases; ROC Analysis; Signal Transduction; Signal Transduction Systems; Signaling; Site; Spores; Staging; Supporting Cell; Tetanus; Time; Tissue Growth; Toxico-Infectious Botulism; trans acting element; Transcriptional Regulatory Elements; Translocation, Genetic; treatment of bacterial diseases; treatment of bacterial infectious disease
Relevance: This proposal focuses on the fundamental problem of how gene expression is coordinated with morphological changes during formation of spores by Bacillus subtilis. All the key sporulation regulatory genes are also found in related pathogens, including B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile. Emphasis is placed on how altering the timing of signaling can change the developmental path taken
Project start date: 1986-07-01
Project end date: 2013-02-28
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-07-070
5R01GM043577-23 (2011): $334125
PRIORITIZED CLINICAL DECISION SUPPORT TO REDUCE CARDIOVASCULAR RISK
J Patrick, Senior Clinical Investigator
Healthpartners Research Foundationcity: Minneapolis country: United States (us)
Grant 5R01HL102144-02 from National Heart, Lung, And Blood Institute
Abstract: The objective of this project is to develop and implement sophisticated point-of-care EHR-based clinical decision support that (a) identifies and (b) prioritizes all available evidence-based treatment options to reduce a given patient´s cardiovascular risk (CVR). After developing the EHR-based decision support intervention, we will test its impact on CVR, the components of CVR, in a group randomized trial that includes 18 primary care clinics, 60 primary care physicians, and 18,000 adults with moderate or high CVR. This approach, if successful, will (a) improve chronic disease outcomes and reduce CVR for about 35% of the U.S. adult population, (b) maximize the clinical return on the massive investments that are increasingly being made in sophisticated outpatient EHR systems, and (c) provide a model for how to use EHR technology support to deliver "personalized medicine" in primary care settings. The objective of this project is to develop and implement sophisticated point-of-care EHR-based clinical decision support that (a) identifies and (b) prioritizes all available evidence-based treatment options to reduce a given patient´s cardiovascular risk (CVR). The prioritized list of treatment options is provided in different formats to both the primary care physician (PCP) and patient at the time of each office visit made by a patient with moderate to high CVR and sub-optimally controlled and potentially reversible CVR factors. Available evidence-based treatment options are prioritized based on the magnitude of potential CVR reduction of each treatment option. This intervention strategy, referred to as Prioritized Clinical Decision Support (PCS), is specifically designed for widespread use in primary care settings and has the potential to substantially augment current efforts to control CVR in the 35% of American adults with 10-year Framingham CVR of 10% or higher. To assess the ability of the PCS intervention to reduce CVR in adults, we will randomize 18 primary care clinics with 60 primary care physicians (PCPs) and approximately 18,000 eligible adults with baseline Framingham 10-year risk of a major CV event (either heart attack or stroke) of 10% or more into one of two experimental conditions Group 1 includes 9 clinics (with 30 PCPs and 9,000 patients) that will receive prioritized clinical decision support (PCS) to reduce CVR at the time of each clinical encounter made by an eligible adult. Group 2 includes 9 clinics (with 30 PCPs and 9,000 patients) that receive no study intervention and constitute a usual care control group. The study will formally test the hypothesis that after control for baseline CVR, post- intervention 10-year Framingham CVR will be better in Group 1 than Group 2 at 12 and 24 months after start of the intervention. In addition, impact of the intervention on specific components of CVR (BP, lipids, glucose, aspirin use, and smoking) will be assessed, and the cost-effectiveness of the intervention will be quantified. This innovative project builds upon 10 years of prior work by our research team, and extends prior successful EHR clinical decision support interventions by introducing prioritization, by providing decision support to both patients and PCPs at the time of the office visit, and by extending the decision support across the broad and critically important clinical terrain of CVR reduction. The results of this project, whether positive or negative, will extend our understanding of how to maximize the clinical return on massive public and private sector investments now being made in sophisticated outpatient EHR systems. If successful, this decision support tool could be broadly used to both standardize and personalize care delivered by case managers, pharmacists, and other providers in a wide range of care delivery configurations
Keywords: Address; Adult; Affect; Algorithms; American; Aspirin; base; Body mass index; cardiovascular risk factor; care delivery; Caring; Case Manager; Chronic Disease; Clinic; Clinic Visits; Clinical; Clinical Trials; Control Groups; cost; cost effectiveness; Data; design; Disease Outcome; Effectiveness of Interventions; Event; Evidence based treatment; Funding; Glucose; group intervention; improved; innovation; Intervention; Intervention Studies; Investments; Lead; Lipids; Mediator of activation protein; Medicine; Methods; Modeling; Myocardial Infarction; novel; Nurses; Office Visits; Outpatients; Patients; Pharmacists; Phase; point of care; Population; post intervention; Primary Care Physician; primary care setting; Primary Health Care; Private Sector; Provider; public health relevance; Public Sector; Randomized; randomized trial; Research; Resources; Risk; Risk Reduction; Simulate; Smoking; stroke; Study Subject; System; Technology; Testing; Time; tool; Training; treatment as usual; Twin Multiple Birth; United States National Institutes of Health; Work
Relevance: The objective of this project is to develop and implement sophisticated point-of-care EHR-based clinical decision support that (a) identifies and (b) prioritizes all available evidence-based treatment options to reduce a given patient´s cardiovascular risk (CVR). The prioritized list of treatment options is provided in different formats to both the primary care physician (PCP) and patient at the time of each office visit made by a patient with moderate to high CVR and sub-optimally controlled and potentially reversible CVR factors. Available evidence-based treatment options are prioritized based on the magnitude of potential CVR reduction of each treatment option. This intervention strategy, referred to as Prioritized Clinical Decision Support (PCS), is specifically designed for widespread use in primary care settings and has the potential to substantially augment current efforts to control CVR in the 35% of American adults with 10-year Framingham CVR of 10% or higher. To assess the ability of the PCS intervention to reduce CVR in adults, we will randomize 18 primary care clinics with 60 primary care physicians (PCPs) and approximately 18,000 eligible adults with baseline Framingham 10-year risk of a major CV event (either heart attack or stroke) of 10% or more into one of two experimental conditions: Group 1 includes 9 clinics (with 30 PCPs and 9,000 patients) that will receive prioritized clinical decision support (PCS) to reduce CVR at the time of each clinical encounter made by an eligible adult. Group 2 includes 9 clinics (with 30 PCPs and 9,000 patients) that receive no study intervention and constitute a usual care control group. The study will formally test the hypothesis that after control for baseline CVR, post- intervention 10-year Framingham CVR will be better in Group 1 than Group 2 at 12 and 24 months after start of the intervention. In addition, impact of the intervention on specific components of CVR (BP, lipids, glucose, aspirin use, and smoking) will be assessed, and the cost-effectiveness of the intervention will be quantified. This innovative project builds upon 10 years of prior work by our research team, and extends prior successful EHR clinical decision support interventions by introducing prioritization, by providing decision support to both patients and PCPs at the time of the office visit, and by extending the decision support across the broad and critically important clinical terrain of CVR reduction. The results of this project, whether positive or negative, will extend our understanding of how to maximize the clinical return on massive public and private sector investments now being made in sophisticated outpatient EHR systems. If successful, this decision support tool could be broadly used to both standardize and personalize care delivered by case managers, pharmacists, and other providers in a wide range of care delivery configurations
Project start date: 2010-07-01
Project end date: 2015-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-07-070
5R01HL102144-02 (2011): $677519
MULTIFUNCTIONAL PEG HYDROGEL NANO/MICROPARTICLES FOR TARGETED TREATMENT OF NSCLC
J Patrick, Parke-davis Chair Professor
Rutgers The St Univ Of Nj New Brunswickcity: New Brunswick country: United States (us)
Grant 1R01CA155061-01 from National Cancer Institute
Abstract: The long-term goal of the proposed research program is to develop an intravenously (IV) administered lung- targeted nanoparticle (NP)/gel microparticle (GMP) delivery system for the treatment of non-small cell lung cancer (NSCLC). After the initial diagnosis, greater than half of the patients with localized lung cancer survive at least 5 years suggesting a benefit to an approach that limits metastatic spread from the primary lung cancer. While targeting is an effective approach for improving drug concentrations and minimizing side effects, the options for lung targeting are narrow. Thus, targeted lung delivery approaches for treating NSCLC are urgently needed. Two levels of targeting are proposed. The first is passive targeting. GMPs selectively accumulate in the lung after IV administration. Our compelling preliminary data demonstrates that passive targeting achieves a 10-fold increase in anti-cancer drug potency and 10-fold lower peak systemic drug concentrations. The second is active targeting. Two types of NPs are proposed to achieve active targeting. Using a novel fabrication process, high drug loading into NPs is achieved that overcomes the solubility limitations of hydrophobic cancer drugs. The NP surfaces are functionalized with ligands that selectively target cancer cells. The second NP group is also functionalized with cell surface ligands, however, instead of delivering drug cargo selectively inside the cancer cell, these NPs are engineered to tightly bind to cancer cell surface receptors and remain there in order to inhibit the metastatic signaling cascade. Once the GMPs passively accumulate in the lung, the NPs imbedded in the GMP diffuse out and seek cancer cells resulting in an extraordinary degree of targeting specificity. Three specific aims are proposed AIM 1 Engineer and evaluate a series of GMPs to achieve (a) optimal passive lung targeting efficiency, retention and elimination and (b) minimal pulmonary toxicity (structural and functional alterations and inflammation) in normal mice and in an orthotropic mouse model of lung cancer. AIM 2 Design, fabricate, and assess NPs and GMPs that enhance the pro-apoptotic effect of camptothecin (CPT). Actively targeted NPs will be developed that specifically deliver CPT and alpha lipoic acid (ALA) to lung cancer cells to exploit synergy in tumor cell apoptosis induced by these two chemotherapeutic agents. AIM 3 Design, fabricate, and assess CXCR4/7-targeted NPs and GMPs that reduce the occurrence of metastasis. Two active targeting approaches will be investigated (1) direct CXCR4/7 receptor binding and (2) inhibition of downstream pro-metastatic signaling factors NF-kB, ERK and/or MMP-9. If successful, an injectable lung targeted drug delivery system will be produced that (1) utilizes passive targeting to exploit the natural flow-filtration pattern of the lung to achieve high local and minimal systemic drug concentrations; (2) exploits synergy in chemotherapy-induced tumor cell apoptosis and active targeting to reduce the required effective drug and MP doses; and (3) utilizes active targeting to reduce the occurrence of metastatic lesions by interfering with the CXCR4/7 - CXCL12 chemokine pathway. Lung cancer is currently the leading cause of cancer deaths in both men and women in the United States and Non-Small Cell Lung Cancer (NSCLC) accounts for the vast majority of lung cancer cases. There is a pressing need to develop new treatment approaches for this highly fatal disease. This project involves the development and evaluation of a novel targeted delivery system (injected intravenously) that uses nanoparticles imbedded into microparticles to deliver chemotherapeutic drugs and other agents specifically to the lungs of patients in order to treat NSCLC and reduce therapy-limiting side effects
Keywords: (S)-4-ethyl-4-hydroxy-1H-pyrano-[3`, 4`[{..}]6, 7]indolozino[1, 2-b]quinoline-3, 14(4H, 12H)-dione; 1, 2-Dithiolane-3-pentanoic acid; 1H-Pyrano(3`, 4`[{..}]6, 7)indolizino(1, 2-b)quinoline-3, 14(4H, 12H)-dione, 4-ethyl-4-hydroxy-, (S)-; 1H-Pyrano[3`, 3`.6, 7]indolizino[1, 2-b]quinoline-3, 14(4H, 12H)-dione, 4-ethyl-4hydroxy-(S)-(9CI); 2-Naphthacenecarboxamide, 4-(dimethylamino)-1, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-1, 11-dioxo-, (4S-(4alpha, 4aalpha, 5alpha, 5aalpha, 6alpha, 12aalpha))-; 20-(S)-camptothecine; 21, 22-secocamptothecin-21-oic acid lactone; 92-kDa Gelatinase; 92-kDa Type IV Collagenase; absorption; Absorption; Accounting; Adherence; Adherence (attribute); Adverse effects; Affinity; alpha-6-Deoxyoxytetracycline; alpha-Lipoic Acid; Anti-Cancer Agents; Anti-Tumor Agents; Anti-Tumor Drugs; anticancer agent; anticancer drug; Antineoplastic Agents; Antineoplastic Drugs; Antineoplastics; Antiproliferative Agents; Antiproliferative Drugs; Anzatax; Apoptosis; Apoptosis Pathway; Apoptotic; Asotax; Aspiration, Respiratory; Binding; Binding (Molecular Function); biological signal transduction; Body Tissues; Breathing; Bristaxol; Camptothecin; Cancer Cause; cancer cell; Cancer Drug; Cancer Etiology; cancer metastasis; Cancer of Lung; Cancer Patient; Carcinoma, Non-Small-Cell Lung; Caring; caspase; Cell Communication and Signaling; Cell Death, Programmed; Cell Signaling; Cell surface; Cell Surface Receptors; Cell-Death Protease; Cessation of life; chemoattractant cytokine; chemokine; chemotherapeutic agent; Chemotherapeutic Agents, Neoplastic Disease; chemotherapy; CXC-R4; CXCL12; CXCL12 gene; CXCR-4; CXCR4; CXCR4 gene; cystein protease; cystein proteinase; cysteine endopeptidase; Cytokines, Chemotactic; cytotoxic; D2S201E; Data; Death; design; designing; Development; Diagnosis; Diffuse; Disease; disease/disorder; Disorder; Dose; Doxycycline; Drug Delivery; Drug Delivery Systems; Drug Targeting; Drug Targetings; drug/agent; Drugs; Engineering; Engineerings; Evaluation; FB22; Filtration; Forecast of outcome; Fractionation, Filtration; Gel; Gelatinase B; Goals; HM89; Homologous Chemotactic Cytokines; HSY3RR; Hydrogels; ICE-like protease; Immunoglobulin Enhancer-Binding Protein; improved; Inflammation; Inflammatory; INFLM; Inhalation; Inhaling; Injectable; inspiration; Inspiration, Respiratory; Intercrines; Intracellular Communication and Signaling; kappa B Enhancer Binding Protein; LAP3; LCR1; LESTR; Life; Ligands; Lipoic Acid; Lung; lung cancer; lung function; Lung Neoplasms; macrophage; Macrophage Gelatinase; Malignant Cell; Malignant neoplasm of lung; Malignant Tumor of the Lung; Mammals, Mice; Matrix Metalloproteinase-9; Medication; men; men`s; Metastasis; Metastasize; Metastatic Lesion; Metastatic Neoplasm; Metastatic Tumor; Mice; migration; MMP-9; MMP-9 Protein; MMP9; Molecular Interaction; mouse model; Murine; Mus; nano; nano particle; nanoparticle; natural flow; Neoplasm Metastasis; neoplastic cell; NF-kappa B; NF-kappaB; NF-kB; NFKB; Non-Small Cell Lung Cancer; Non-Small-Cell Lung Carcinoma; nonsmall cell lung cancer; novel; NPY3R; NPYR; NPYRL; NPYY3R; NSCLC; NSCLC - Non-Small Cell Lung Cancer; Nuclear Factor kappa B; nuclear factor kappa beta; Nuclear Transcription Factor NF-kB; outcome forecast; Paclitaxel; Paclitaxel (Taxol); pathway; Pathway interactions; Patients; Pattern; PBSF; Peptide Fragments; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacodynamics; Platinum; Platinum Black; Praxel; Prevention; Process; Process of absorption; Prognosis; programs; Programs (PT); Programs [Publication Type]; Pt element; public health relevance; pulmonary; Pulmonary Cancer; Pulmonary malignant Neoplasm; Pulmonary Neoplasms; receptor binding; Research; residence; Resistance; resistant; respiratory function; Respiratory physiology; Respiratory System, Lung; SCYB12; SDF-1A; SDF-1B; SDF1; SDF1A; SDF1B; Secondary Neoplasm; Secondary Tumor; Series; side effect; Signal Transduction; Signal Transduction Systems; Signaling; SIS cytokines; site targeted delivery; Solubility; Specificity; Staging; Structure; Surface; System; System, LOINC Axis 4; targeted delivery; Taxol; Taxol (Old NSC); Taxol A; Taxol Konzentrat; therapy adverse effect; Thioctic Acid; Time; Tissues; TLSF-A; TLSF-B; Toxic effect; Toxicities; TPAR1; Transcription Factor NF-kB; treatment adverse effect; Treatment Side Effects; Tumor Cell; Tumor Cell Migration; Tumor of the Lung; Tumor-Specific Treatment Agents; Type V Collagenase; United States; Vibramycin; Viral; vMIP-II; Woman
Relevance: NARRATIVE Lung cancer is currently the leading cause of cancer deaths in both men and women in the United States and Non-Small Cell Lung Cancer (NSCLC) accounts for the vast majority of lung cancer cases. There is a pressing need to develop new treatment approaches for this highly fatal disease. This project involves the development and evaluation of a novel targeted delivery system (injected intravenously) that uses nanoparticles imbedded into microparticles to deliver chemotherapeutic drugs and other agents specifically to the lungs of patients in order to treat NSCLC and reduce therapy-limiting side effects
Project start date: 2011-01-01
Project end date: 2015-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-10-067
1R01CA155061-01 (2011): $387246
STRUCTURES AND FUNCTIONS OF THE HUMAN JOSEPHIN DOMAIN-CONTAINING PROTEINS
J Patrick
Drexel Universitycity: Philadelphia country: United States (us)
Grant 5R01NS065140-03 from National Institute Of Neurological Disorders And Stroke
Abstract: The Josephin domain-containing proteins are one of the five major families of deubiquitinating enzymes (DUBs). The founding member of the family is ataxin-3, a polyglutamine protein and the causative agent of the most common inherited ataxia, spinal cerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease). Ataxin-3´s DUB activity resides in the molecule´s N-terminal half, the so-called Josephin domain. Ataxin-3 is linked to many cellular processes that are related to maintaining protein homeostasis, including the transport of misfolded proteins to aggresomes and the flux of proteins through the endoplasmic reticulum-associated degradation pathway (ERAD). Ataxin-3 can also suppress the toxicity of expanded repeat polyglutamine domains. All of these functions require DUB activity, establishing the biological significance of the Josephin domain and hinting at a link between Josephin DUB activity and neurodegeneration induced by protein misfolding. Three homologs of ataxin-3 are encoded in the human genome The ataxin-3-like protein (AT3L), Josephin-1, and Josephin-2. All three possess DUB activity, but differ substantially in catalytic efficiency and specificity. Josephin domain-containing homologs are conserved in most eukaryotes, including plants and protozoans, implying that this domain and the DUB activity it expresses are responsible for valuable biological functions. We propose to analyze the molecular structure and function of the human Josephin domain-containing proteins in order to understand how they recognize and act upon substrates and other interacting proteins. We will use X-ray crystallography to determine structures for different Josephin domains, alone and in complex with ubiquitin substrates; characterize the DUB activities of the four human Josephin domain-containing proteins, assessing how they bind and cleave both small and large ubiquitin substrates; explore their ubiquitin-binding activities; and probe the interactions of ataxin-3 with its cellular binding partners. The Josephin domain proteins appear to function in quality control pathways in human cells. Understanding how the Josephin proteins function will help reveal how cells protect themselves from the potentially toxic effects of protein misfolding. The insights obtained from this work will inform efforts to design therapies for disorders in which the cell´s quality control pathways are disrupted, such as Huntington´s disease, Alzheimer´s disease, and Parkinson´s disease
Keywords: Alzheimer`s Disease; Ataxia; base; Binding (Molecular Function); Biochemical; Biological; Biological Process; C-terminal; Cell physiology; Cells; Cerebellar Ataxia; Chemicals; Cleaved cell; Complex; Cysteine Protease; Degradation Pathway; Deubiquitinating Enzyme; Disease; Distant; Endoplasmic Reticulum; Enzymes; Eukaryota; Family; Family member; Glutamine; Homeostasis; Homologous Gene; Human; Human Genome; Huntington Disease; Inherited; insight; Length; Link; Machado-Joseph Disease; member; Methods; MJD1 protein; Molecular; Molecular Probes; Molecular Structure; N-terminal; Nerve Degeneration; Parkinson Disease; Pathway interactions; Plants; Play; polyglutamine; Polyubiquitin; preference; protein function; protein misfolding; Proteins; public health relevance; Quality Control; Relative (related person); research study; Role; Specificity; Spinal; structural biology; Structure; Tertiary Protein Structure; Testing; therapy design; Toxic effect; Ubiquitin; Work; X-Ray Crystallography
Relevance: The Josephin domain proteins appear to function in quality control pathways in human cells. Understanding how the Josephin proteins function will help reveal how cells protect themselves from the potentially toxic effects of protein misfolding. The insights obtained from this work will inform efforts to design therapies for disorders in which the cell´s quality control pathways are disrupted, such as Huntington´s disease, Alzheimer´s disease, and Parkinson´s disease
Project start date: 2009-09-30
Project end date: 2013-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-07-070
5R01NS065140-03 (2011): $331209
HAZMAT TRAINING AT DOE NUCLEAR WEAPONS COMPLEX
J Patrick
International Association Fire Fighterscity: Washington country: United States (us)
Grant 5U45ES009759-20 from National Institute Of Environmental Health Sciences
Abstract: The International Association of Fire Fighters (lAFF) is requesting $671,680 direct cost and $53,734 F&A during the initial budget period and $3,566,045 direct costs and $ 285,284 F&A for the total project period of the HAZMAT Training at DOE Nuclear Weapons Complex Cooperative Agreement. The lAFF proposes to continue its training plan to train fire fighters in specialty courses, primarily to the hazmat technician level through direct delivery programs. The lAFF will train additional fire fighters nationwide, in other specialized course curricula already developed by the lAFF. The lAFF will use existing curricula, already proven to be effective, to train fire fighters, conducting curricula revisions as necessary to meet and exceed updated national consensus standards and federal standards and regulations. Aside from hazardous materials, the focus of the training will revolve around health and safety, with the intent that students will perform their duties in a safe and effective manner after training. While the primary focus of the lAFF/DOE training will be within 150 miles of a DOE site, the lAFF will expand the training radius even further to meet the needs of first responders. This expanded radius will better prepare responders who may be dispatched to a specific DOE facility through the Emergency Management Assistance Compact (EMAC). EMAC, established in 1996, is a mutual aid agreement and partnership between member states. EMAC offers a responsive and straightforward system for states to send personnel and equipment to help disaster relief efforts in other states. When resources are overwhelmed, EMAC helps to fill the shortfalls. EMAC allows states to ask for assistance as needed for any type of emergency. Based on the risk and vulnerability posed by DOE cleanup sites, there is a strong possibility that personnel from surrounding states as well as states located across the country could respond to a large scale disaster involving one of our DOE partners. DOE sites pose unique and significant threats to responders. An estimated 36% of fire departments involved in hazmat response do formal training to their responding personnel. In 2008,114 fire fighters were killed in the line of duty. These statistics place first responders at great risk, and underscore the need for renewed funding to train first responders in hazardous materials, with a focus on health and safety
Keywords: Agreement; base; Budgets; Complex; Consensus; Country; Direct Costs; Disasters; Educational Curriculum; emergency service/first responder; Emergency Situation; Equipment; Fire - disasters; Funding; Hazardous Substances; Health; Human Resources; International; Killings; medical specialties; meetings; member; Nuclear Weapon; programs; Radial; Regulation; Resources; response; Risk; Safety; Site; statistics; Students; System; Training; U-Series Cooperative Agreements; Update
Project start date: 1992-09-16
Project end date: 2015-08-31
Budget start date: 23-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: RFA-ES-09-003
5U45ES009759-20 (2011): $661846
HAZARDOUS MATERIAL WORKER HEALTH AND SAFETY TRAINING (U45) COOPERATIVE AGREEMENT
J Patrick
International Association Fire Fighterscity: Washington country: United States (us)
Grant 5U45ES006167-20 from National Institute Of Environmental Health Sciences
Abstract: The International Association of Fire Fighters (lAFF) is requesting $1,058,078 in direct costs and $84,646 in F&A during the initial budget period, and $5,617,477 in direct costs and $449,398 in F&A for the total project period of the Worker Health and Safety Training Cooperative Agreement. The lAFF application includes two of the four program areas Hazardous Waste Worker Training Program (HWWTP) and Hazardous Materials Disaster Preparedness Training Program (HDPTP). The lAFF proposes to continue to train fire fighters to the hazardous materials technician level through direct delivery programs nationwide. In addition, the lAFF will train fire fighters in other specialized course curricula already developed by the lAFF. The lAFF will use existing curricula, already proven to be effective, to train fire fighters, conducting curricula revisions as necessary to meet and exceed updated national consensus standards, federal standards and regulations. Aside from hazardous materials, the focus of the training will revolve around health and safety, with the intent that students will perform their duties in a safe and effective manner after training. In order to operate effectively in this new environment, emergency responders require incident command, safety management training at large scale incidents and advanced training, especially at the technician level. Each year of the cooperative agreement, the lAFF will train an average of 1,000 students in the technician and train-the-trainer curricula. In addition, the lAFF will reach an average of 750 students with an adapted incident management course which emphasizes safety management during disaster response. Hazardous Waste Worker Training Program (HWWTP)
Relevance: Less than 10% of fire department calls involve fire. DOT reports 170,527 hazmat incidents with 2,857 injuries and 137 fatalities from 1999 to 2008. In 2008,114 fire fighters were killed in the line of duty. An estimated 36% of fire departments involved in hazmat response do training. These statistics underscore the risk, and need for funding to train responders in hazmats, with a focus on health & safety
Project start date: 1992-09-16
Project end date: 2015-07-31
Budget start date: 4-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: RFA-ES-09-004
5U45ES006167-20 (2011): $787415
Sponsored Links Excellgen http://Excellgen.com
INDIANA UNIVERSITY MELVIN AND BREN SIMON CANCER CENTER SUPPORT GRANT
J Patrick
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 3P30CA082709-13S1 from National Cancer Institute
Abstract: The Indiana University Melvin and Bren Simon Cancer Center is a matrix Cancer Center that organizes and facilitates cancer research, education, patient care, and cancer control and prevention. Our mission is to advance the understanding, prevention and treatment of cancer throughout Indiana and the world with patient centered care, acceleration of promising science and collaborative educational programs. This application seeks funds for the Center´s four research programs, six shared facilities, Protocol-Specific Research, Protocol Review and Monitoring System, and Data and Safety Monitoring. In addition, funds are requested for Administration, Program Planning and Evaluation, Developmental Funds, and Senior Leaders. The research programs have been organized and developed to be highly interactive, allowing for successful collaboration among basic, clinical, and population science researchers. The research programs are 1) Cancer Control, 2) Breast Cancer, 3) Experimental and Developmental Therapeutics, 4) Hematopoiesis, Microenvironment and Immunology. Supporting the members of these programs are six shared resources Biological Microscopy, Biostatistics and Data Management, Clinical Research Office, Flow Cytometry, Chemical Genomics and Clinical Pharmacology Analytical Analysis
Keywords: Acceleration; anticancer research; Basic Science; Biological; Biometry; Cancer Center; Cancer Center Support Grant; Cancer Control; cancer prevention; cancer therapy; Chemicals; Clinical Pharmacology; Clinical Research; Clinical Sciences; Collaborations; data management; Development; Developmental Therapeutics Program; Educational aspects; Evaluation; Flow Cytometry; Funding; Genomics; Hematopoiesis; Immunology; Indiana; Information Systems; malignant breast neoplasm; member; Microscopy; Mission; Monitor; Patient Care; Patient-Centered Care; Population Sciences; Prevention; programs; Protocols documentation; Research; Research Personnel; Resource Sharing; Safety; Science; Universities
Project start date: 1999-09-22
Project end date: 2013-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
3P30CA082709-13S1 (2011): $108772
3P30CA082709-13S2 (2011): $49994
5P30CA082709-13 (2011): $1145097
EASTERN COOPERATIVE ONCOLOGY GROUP
J Patrick
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 5U10CA049883-23 from National Cancer Institute
Abstract: The Indiana University Melvin and Bren Simon Cancer Center (lUSCC) continues to play major leadership roles within ECOG and especially in the design and completion of pivotal research trials. Dr. Loehrer has served on several appointed and elected positions during this past grant cycle including the Nominating Committee, Fiscal Oversight Committee and the Research Foundation Board. Dr. Sledge is the current Chair of the Breast Committee; Dr. David Flockhart is the current Chair of Developmental Therapeutics, while several other faculty and staff have served as chairs, co-chairs or participated in a broad number of ECOG committees. Our faculty have been PIs on numerous Phase II and III prospective trials. Notable examples include E2100, lead by Dr. Kathy Miller, which ultimately lead to the approval of bevacizumab by the FDA for the treatment of advanced Breast Cancer. Drs. Loehrer and Cardenes were co-PIs on E4201 which demonstrated for the first time in modern era that radiation in addition to gemcitabine chemotherapy has a survival advantage over chemotherapy alone. Our faculty have been broadly involved in many committees including GU, Gl, Leukemia, Myeloma, Breast, Thoracic, Developmental Therapeutics, Pharmacy and Data Management Committees. Some of our affiliates have also had leadership positions in the Breast and Thoracic Committees. In the fall of 2008, the lUSCC opened a new 150,000 inpatient and outpatient facility and in April, 2009 the Joseph Walther Building was opened which virtually doubles the amount of basic research space on campus dedicated for cancer related activities. Despite numerous external pressures, our annual accrual has remained strong and efforts to increase accrual for women and minorities, especially at our county-affiliated hospital, have begun to take hold. lUSCC remains committed to the administrative and scientific growth of the ECOG as exemplified by our leadership, academic contributions, patient accrual and diverse participation at many levels in the organization. Our goal for the coming grant cycle is to increase the participation by our affiliate partners and to increase minority accrual to clinical trials at our parent institution. RELEVANCE The lUSCC is the only NCI-Designated Cancer Center that treats patients in Indiana. Our long standing commitment for clinical research has been illustrated by pilot trials conducted at lUSCC and taken to the cooperative oncology groups (ECOG) for verification. Standards of care adopted by national forums for the treatment of germ cell tumors, lung cancer, thymoma and breast cancer have emerged from investigator-initiated trials from lUSCC faculty. Our impact upon the public health is clear and well documented
Keywords: Adopted; Basic Science; bevacizumab; Breast; Cancer Center; Caring; chemotherapy; Chest; Clinical Research; Clinical Trials; Commit; County; data management; design; Developmental Therapeutics Program; Eastern Cooperative Oncology Group; Faculty; falls; Foundations; gemcitabine; Germ cell tumor; Goals; Grant; Growth; Hospitals; Indiana; Inpatients; Institution; Lead; Leadership; leukemia; malignant breast neoplasm; Malignant neoplasm of lung; Malignant Neoplasms; Minority; Multiple Myeloma; NCI-Designated Cancer Center; Oncology Group; Outpatients; Parents; Patients; Pharmacy facility; Phase; pilot trial; Play; Positioning Attribute; pressure; prospective; public health medicine (field); Radiation; Research; Research Personnel; Role; Thymoma; Time; Universities; Woman
Relevance: RELEVANCE: The lUSCC is the only NCI-Designated Cancer Center that treats patients in Indiana. Our long standing commitment for clinical research has been illustrated by pilot trials conducted at lUSCC and taken to the cooperative oncology groups (ECOG) for verification. Standards of care adopted by national forums for the treatment of germ cell tumors, lung cancer, thymoma and breast cancer have emerged from investigator-initiated trials from lUSCC faculty. Our impact upon the public health is clear and well documented
Project start date: 1989-05-01
Project end date: 2016-04-30
Budget start date: 13-JUN-2011
Budget end date: 30-APR-2012
5U10CA049883-23 (2011): $259060
REGULATION OF CELL POLARITY AND EXOCYTOSIS
J Patrick, Professor
University Of North Carolina Chapel Hillcity: Chapel Hill country: United States (us)
Grant 5R01GM054712-14 from National Institute Of General Medical Sciences
Abstract: The goal of this proposal is to understand the mechanism by which eukaryotic cells target new membrane growth and secretion to specific sites on the cell surface and how this is coordinated with changes in cell polarity during the cell cycle. In this proposal we will examine the specific role of Lgl/Sro7 and Rho/Cdc42 protein families in this process. The Lgl/Sro7 family of proteins, first.identified as a tumor suppressor in Drosophila, is found in all eukaryotic cells and is likely to have a highly conserved function in regulation of polarity and exocytosis. We have characterized homologs of this family in both yeast and mammalian epithelial cells where they are found in physical association with a specific set of SNARE proteins. We will test the hypothesis that Lgl family members have a conserved structure and function in polarized exocytosis and may act as effectors of Rab GTPases in mediating SNARE-dependent vesicle fusion during polarized growth. Genetic analyses performed in our lab have led to the identification of a direct role for Rho/Cdc42 GTPases in exocytosis. In particular we have found two Rho GTPases, Rho3 and Cdc42, that function in a pathway which involves spatial regulation of exocytosis through direct activation of a multisubunit complex known as the Exocyst. In this proposal we will take a comprehensive approach to identify the molecular mechanism by which Sro7, Rho3, and Cdc42 function in the regulation of polarized exocytosis. Ultimately understanding the molecular details of these processes may allow the development of new approaches and novel therapeutics to combating cancer, or type II diabetes, as well as other diseases in which regulation of cell surface trafficking is central to the etiology of the disease
Keywords: Alleles; Binding (Molecular Function); Biochemical; cdc42 GTP-Binding Protein; Cell Cycle; Cell membrane; Cell Polarity; Cell surface; Chimera organism; combat; Complement; Complex; Development; Disease; Docking; Drosophila genus; Epithelial Cells; Etiology; Eukaryotic Cell; Exocytosis; Family; Family member; Funding; gain of function; Genes; Genetic; genetic analysis; Goals; Golgi Apparatus; Growth; Guanosine Triphosphate Phosphohydrolases; Homologous Gene; in vitro Assay; in vivo; insight; Laboratories; Liposomes; Malignant Neoplasms; Mammals; Mediating; Membrane; Modeling; Molecular; Monomeric GTP-Binding Proteins; mutant; Nature; Non-Insulin-Dependent Diabetes Mellitus; novel; novel strategies; novel therapeutics; Pathway interactions; Process; programs; Protein Family; Proteins; rab GTP-Binding Proteins; reconstitution; Regulation; Regulation of Exocytosis; Research Personnel; rho; rho GTP-Binding Proteins; Role; Site; SNAP receptor; Specificity; Structure; Surface; target SNARE proteins; Testing; trafficking; Tumor Suppressor Proteins; Vesicle; Work; Yeasts
Project start date: 1998-05-01
Project end date: 2012-04-30
Budget start date: 1-MAY-2010
Budget end date: 30-APR-2012
5R01GM054712-14 (2010): $360477
GENETICALLY MODIFED TISSUE ENGINEERED IN VITRO HUMAN MODELS
J Patrick, Senior Scientist
Mattek Corporationcity: Ashland country: United States (us)
Grant 1R43GM084551-01A1 from National Institute Of General Medical Sciences
Abstract: The goal of the current proposal is to apply state of the art gene modification technology including lentiviral delivery systems and RNA interference technology to commercially available tissue engineered human in vitro models. These models will consist of differentiated 3-D epidermal cultures and tracheal/bronchial epithelial cultures, as well as epidermal and airway epithelia co-cultured with mesenchymal cells. In Phase I research, the technology will be used to produce 3 types of genetically modified tissue engineered culture products 1) stable addition of a functional gene, 2) stable silencing of a gene, and 3) stable introduction of a reporter for detection of gene activation. During Phase II, the techniques will be applied to additional tissue engineered human in vitro models, and the inventory of available gene modified products will be expanded. These proposed commercially available in vitro model systems will provide researchers in the pharmaceutical industry and academic research laboratories a readily available means for studying the functional genomics of nearly any gene in human epithelial cells, as well as crosstalk between epithelial and stromal cells in the differentiated organotypic state. Use of these models will aid in identification and validation of targets for development of novel therapeutics for treatment of human skin and airway epithelial diseases including cancers, chronic wounds, blistering diseases, scarring, and airway remodeling associated with asthma and COPD. The gene modified tissue engineered models to be produced by the current project will provide researchers in the pharmaceutical industry and academic research laboratories a readily available means for studying the functional genomics of nearly any gene in human epithelial cells, as well as crosstalk between epithelial and stromal cells in the differentiated organotypic state. The models will be utilized to identify and validate targets for the development of novel therapeutics for treatment of human skin and airway epithelial diseases including cancers, chronic wounds, blistering diseases, scarring, and airway remodeling associated with asthma and COPD
Keywords: 3-10C; 3-D; 3-Dimensional; Adherent Culture; airway epithelium; airway remodeling; AMCF-I; Anaplastic; Apical; Apoptosis; Apoptosis Pathway; Arts; Aspiration, Respiratory; Asthma; b-ENAP; base; Basic Research; Basic Science; Biological Models; biological signal transduction; Bleb; Blister; Body Tissues; Breathing; Bronchial Asthma; Bulla; Bullous Lesion; Cancers; Carcinogenesis Mechanism; Cell Communication and Signaling; Cell Culture Techniques; Cell Death, Programmed; Cell Function; Cell Line; Cell Lines, Strains; Cell physiology; Cell Process; Cell Signaling; cell type; CellLine; Cells; Cellular Function; Cellular Physiology; Cellular Process; CFTR; CFTR Protein; Cholest-7-en-6-one, 2, 3, 14, 22, 25-pentahydroxy-, (2beta, 3beta, 5beta, 22R)-; Chronic; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease; Cicatrix; CLG; Client; Clinical Trials, Phase II; Co-culture; COAD; Cocultivation; Coculture; Coculture Techniques; Contracting Opportunities; Contracts; COPD; Cornea; corneal; cosmetic product; Cosmetics; cross-link; crosslink; Cryopreserved Cell; cultured cell line; CXCL8; Cystic Fibrosis Transmembrane Conductance Regulator; cystic fibrosis transmembrane regulator; cytokine; cytotoxicity; Defensins; Dendritic Cells; Deoxyribonucleic Acid; Dermal; Detection; Development; Dimensions; Disease; disease/disorder; Disorder; DNA; DNA Maintenance; DNA Repair Enzymes; DNA Stability; Drug Industry; Drug Interactions; drug metabolism; drug/agent; Drugs; Ecdysone; ELISA; engineered tissue; Environment; environmental agent; Enzyme-Linked Immunosorbent Assay; Enzymes; Epithelial; Epithelial Cells; Equipment and supply inventories; experiment; experimental research; experimental study; Feedback; Fibroblast Collagenase; Fibroblasts; Fibrosis; functional genomics; Funding; Future; GADD45; GCP-1; GCP1; Gene Activation; Gene Expression; gene function; gene product; Gene-Modified; Genes; Genes, p53; Genetic; Genital System, Female, Vagina; Genome; Genomics; genotoxicity; GFP; Gingiva; Gingival; Goals; Green Fluorescent Proteins; H2O2; Health; Horny Layer; Household Products; Household Supplies; Human; human disease; Human Genome; human tissue; Human, General; Hydrogen Peroxide; Hydrogen Peroxide (H2O2); Hydroperoxide; IL-8; IL8; IL8 gene; immortalized cell; Immunity, Innate; Immunity, Native; Immunity, Natural; Immunity, Non-Specific; In Vitro; in vitro Model; in vivo; Industry; Industry, Pharmaceutic; Inflammation; INFLM; Inhalation; Inhaling; inspiration; Inspiration, Respiratory; interest; Interstitial Collagenase; intervention therapy; Intracellular Communication and Signaling; Inventory; Investigators; K60; keratinocyte; Knock-out; Knockout; knockout gene; Laboratory Research; Lac Repressors; LECT; Lipids; LUCT; Lung; LYNAP; Lytotoxicity; Maintenance; Maintenances; malignancy; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Matrix Metalloproteinase-1; Matrix Metalloproteinases; MDNCF; Medication; Mesenchymal; Messenger RNA; Method LOINC Axis 6; Methodology; Methods; Methods and Techniques; Methods, Other; MMP-1; MMP-1Fibroblast Collagenase; MMP1; MMPs; model development; Model System; Modeling; Models, Biologic; Modification; Molting Hormone; MONAP; Monitor; monolayer; Monolayer culture; mRNA; Mucins; Mucus Glycoprotein; NAF; National Institutes of Health; National Institutes of Health (U.S.); Natural Immunity; neoplasm/cancer; new therapeutics; next generation therapeutics; NIH; Normal Cell; novel; novel therapeutics; Organ; overexpression; Oxidative Stress; P53; pathogen; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Industry; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Phase 2 Clinical Trials; phase 2 study; phase 2 trial; Phase II Clinical Trials; phase II trial; Play; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Process; Production; protein expression; Proteins; Protocol; protocol, phase II; Protocols documentation; public health relevance; pulmonary; Pulmonary Disease, Chronic Obstructive; Quelling; Regulation; Reporter; Research; Research Personnel; research study; Researchers; Respiratory System, Lung; response; reverse transcriptase PCR; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA Silencing; RNA Silencings; RNA, Messenger; RNAi; Role; RT-PCR; RTPCR; Scars; SCYB8; Sequence-Specific Posttranscriptional Gene Silencing; short hairpin RNA; shRNA; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Skin; small hairpin RNA; social role; Staging; Stratum corneum; Stromal Cells; Structure; study, phase II; Subcellular Process; Surface; Suspension Culture; System; System, LOINC Axis 4; T-Cells; T-Lymphocyte; Techniques; Technology; Tetracycline Antibiotic; Tetracyclines; Therapeutic Intervention; thymus derived lymphocyte; Thymus-Dependent Lymphocytes; Tissue Engineering; Tissue Model; tissue repair; Tissues; tool; TP53; TP53 gene; TRP53; TSG-1; Tumor Protein p53 Gene; Undifferentiated; United States National Institutes of Health; Vagina; Vaginal; Validation; Veiled Cells; Vesication; Wound Healing; Wound Repair
Relevance: . The gene modified tissue engineered models to be produced by the current project will provide researchers in the pharmaceutical industry and academic research laboratories a readily available means for studying the functional genomics of nearly any gene in human epithelial cells, as well as crosstalk between epithelial and stromal cells in the differentiated organotypic state. The models will be utilized to identify and validate targets for the development of novel therapeutics for treatment of human skin and airway epithelial diseases including cancers, chronic wounds, blistering diseases, scarring, and airway remodeling associated with asthma and COPD
Project start date: 2009-02-15
Project end date: 2011-02-14
Budget start date: 15-FEB-2009
Budget end date: 14-FEB-2011
PFA/PA: PA-08-050
1R43GM084551-01A1 (2009): $221236
RANDOMIZED CLINICAL TRIALS - WHOLE GENOME STUDIES COORDINATING CENTER
J Patrick, Professor And Chair
University Of Washingtoncity: Seattle country: United States (us)
Grant 5U01HG005157-03 from National Human Genome Research Institute
Abstract: The Department of Biostatistics at the University of Washington proposes to establish a Coordinating Center for a series of genome-wide association studies of treatment response in randomized clinical trials. The Coordinating Center will be administered within the Center for Biomedical Statistics of the Department of Biostatistics and it will take advantage of the experience gained by departmental activities as Coordinating Center for the Geneva project. Geneva is a series of 14 genome-wide association studies within the Gene-Environment Initiative. The new RTC-WGA Coordinating Center will be co-directed by Bruce Weir, Chair of the Department of Biostatistics and PI of the Geneva Coordinating Center, and by Patrick Heagerty, Director of the Center for Biomedical Statistics. They will be joined by Biostatistics faculty Scott Emerson, Ken Rice, Lianne Sheppard, Jon Wakefield, Epidemiology faculty member Annette Fitzpatrick and by Medicine faculty member Bruce Psaty. These faculty have substantial experience in the conduct of both clinical trials and genetic studies, as well as in studying the effects of environmental exposures. They will be able to seek advice from a distinguished advisory panel of Lon Cardon, Tom Fleming, Dick Kronmal and Ross Prentice. The Coordinating Center will provide administration and coordination of all activities for the set of whole-genome analyses of data from participants in clinical trials at study sites. The Center will facilitate harmonization and sharing of phenotypic and genetic data across study sites, the genotyping centers and dbGaP. The Center will assure the integrity of data by implementing appropriate data management procedures and quality control activities. The Coordinating Center will provide statistical support for modeling and selecting options for replication and follow-up studies, and, as appropriate, for selecting targets for sequencing and functional studies as well as analytic support for issues inherent to randomized clinical trials. The Coordinating Center will serve as a resource to facilitate and support all NHGRI whole-genome association studies, including the training of researchers in appropriate statistical methodology and the provision of computer software for statistical analyses. People may respond to treatments for disease in a way that depends on their genetic constitution. There would be many benefits if the possibility that they will have adverse reactions could be predicted on the basis of a simple blood test. The best way to determine the relationship between genetic constitution and response to treatment is with a randomized clinical trial. The coordinating center will manage the data from these trials
Keywords: Adverse reactions; Back; base; Biometry; Blood Tests; Clinical Trials; Code; Communication; computer network; Computer software; Computer Systems; Confidentiality; Constitution; Data; Data Analyses; data integrity; data management; Data Quality; Data Set; Data Storage and Retrieval; database of Genotypes and Phenotypes; design; Development; development policy; Directories; Disease; Documentation; Ensure; Environment; Environmental Exposure; Epidemiology; experience; Faculty; follow-up; Genes; Genetic; Genome; genome wide association study; genome-wide; Genotype; Goals; Group Meetings; Individual; Information Systems; innovation; Manuscripts; Medicine; meetings; member; Methodology; Methods; Modeling; National Human Genome Research Institute; Participant; Phenotype; Preparation; Procedures; programs; public health relevance; Published Directory; Quality Control; Randomized Clinical Trials; Randomized Controlled Trials; Reporting; Research Design; Research Personnel; Resources; response; Rice; Sampling Studies; Scientist; Security; Series; sharing data; Site; statistics; symposium; System; Technology; Time; tool; Training; treatment response; Universities; Washington; web site; working group
Project start date: 2009-09-28
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: RFA-HG-08-005
5U01HG005157-03 (2011): $1218136
EFFECTS OF MTOR INHIBITORS ON MULTIPLE MYELOMA TUMORS
J Patrick, Assistant Researcher
Brentwood Biomedical Research Institutecity: Los Angeles country: United States (us)
Grant 5K01CA111623-05 from National Cancer Institute
Abstract: The AKT signaling pathway is important for the survival of multiple myeloma cells (MM). An important downstream target of AKT is the mammalian target of rapamycin (mTOR), which mediates phosphorylation of p70 and 4E-BP1, factors responsible for ribosome biogenesis and cap-dependent protein translation, respectively. Drugs that target mTOR, such as rapamycin, inhibit cap-dependent translation of critical proteins, resulting in cell cycle arrest and apoptosis. Numerous studies have demonstrated that the sensitivity to the anti-tumor effects of mTOR inhibitors correlates to heightened AKT activity, and we hypothesize that this is because cells with hyperactive AKT function depend upon mTOR-mediated cap-dependent translation of proteins required for survival. In these "high" AKT cells, we expect that Mtor inhibitors block cap-dependent translation of these proteins, leading to cell cycle arrest and apoptosis. In contrast, MM cells with "low" AKT function may utilize non-AKT/mTOR-dependent (i.e. cap-independent) translational pathways to express these critical proteins, making them resistant to mTOR inhibition. The cap-independent salvage pathway is mediated by internal ribosome entry sites (IRESes) located in the 5´UTR of specific mRNAs. In support of this hypothesis, we have recently demonstrated that translation of proteins with known IRES sequences (e.g. c-myc, VEGF) are differently expressed "high" versus "low" AKT MM cells. Therefore, this application will test whether AKT-mediated sensitivity of MM cells to mTOR inhibitors is due to inhibition of the cap-independent translation salvage pathways of critical survival and angiogenic proteins in vitro and in vivo. Will will also test whether the underlying mechanism(s) regulating cap-independent translation is mediated through IRES function of these gene transcripts. This K01 application will specifically provide mentored scientific, academic and career development training to the P.I. during a crucial period in his career and will facilitate his transition to an independent investigator in the field cancer biology
Keywords: 5` Untranslated Regions; 5`UTR; AKT; Akt protein; AKT Signaling Pathway; Alleles; Allelomorphs; analog; angiogenesis; Angiogenic Proteins; Apoptosis; Apoptosis Pathway; Binding; Binding (Molecular Function); Biogenesis; c myc; c-akt protein; c-myc Genes; Cancer Biology; Cancer Patient; career; career development; CCI-779; Cell Cycle Arrest; Cell Cycle Inhibitor 779; Cell Death, Programmed; Cell Growth in Number; Cell Line; Cell Lines, Strains; Cell Multiplication; Cell Proliferation; CellLine; Cells; Cellular Proliferation; clinical investigation; Clinical Trials; Clinical Trials, Unspecified; Critical Paths; Critical Pathways; cultured cell line; Drug Delivery; Drug Delivery Systems; Drug Targeting; Drug Targetings; drug/agent; Drugs; EC 2.7; Face; facial; Figs; Figs - dietary; gene function; gene product; Generalized Growth; Genes; Growth; Hand; HTS1; Human; Human, General; In Vitro; in vivo; in vivo Model; inhibitor; inhibitor/antagonist; Internal Ribosome Entry Segment; Internal Ribosome Entry Site; Investigators; IRES; Kinases; mammalian target of rapamycin (mTOR); Man (Taxonomy); Man, Modern; Mediating; Medication; Mentors; Messenger RNA; Modeling; Molecular Interaction; mRNA; mRNA Leader Sequences; mTOR gene product; mTOR protein; Multiple Myeloma; myeloma; Myeloma, Plasma-Cell; myelomatosis; neoplastic cell; ontogeny; Origin of Life; P126; P70; P82; pathway; Pathway interactions; Pharmaceutic Preparations; Pharmaceutical Preparations; Phosphorylation; Phosphotransferases; PKB protein; pre-clinical; preclinical; protein expression; Protein Kinase B; Protein Phosphorylation; Protein Region; protein-serine-threonine kinase (rac); Proteins; proto-oncogene protein akt; proto-oncogene protein RAC; Proto-Oncogene Proteins c-akt; rac protein kinase; RAC-PK protein; RAFT-1 gene product; Rapamune; Rapamycin; Rapamycin Analog; Rapamycin Analog CCI-779; recruit; Recruitment Activity; Regulation; related to A and C-protein; Research Personnel; Researchers; Resistance; resistant; Ribosome Entry Site; Ribosomes; RNA, Messenger; Role; Sirolimus; Site; social role; ST5; ST5 gene; Structure; Suppression of Tumorigenicity 5; Testing; Tissue Growth; Training; Transcript; Translations; Transphosphorylases; tumor; Tumor Cell; Untranslated Regions; UTRs; v-myc Avian Myelocytomatosis Viral Oncogene Cellular Homolog; Vascular Endothelial Growth Factors; Vegf; VEGFs
Project start date: 2005-08-01
Project end date: 2011-07-31
Budget start date: 1-AUG-2009
Budget end date: 31-JUL-2011
PFA/PA: PAR-03-104
5K01CA111623-05 (2009): $149580
SHARED DECISION-MAKING FOR ELDERLY DEPRESSED PRIMARY CARE PATIENTS
J Patrick, Associate Professor
Weill Medical College Of Cornell Univcity: New York country: United States (us)
Grant 5R01MH084872-03 from National Institute Of Mental Health
Abstract: Shared decision-making (SDM), in contrast to traditional medical decision-making, involves a collaborative process whereby patients articulate personal values and preferences and clinicians provide information to arrive at a mutually-agreed upon treatment decision. SDM may be particularly relevant for depressed individuals, as it seeks to enhance their autonomy and empowerment in a manner that directly addresses the helplessness and hopelessness associated with depression. Shared decision-making interventions are being developed for depression in primary care, but have yet to be adequately tested. It is also unknown whether the same premises regarding shared decision-making´s ability to enhance autonomy and empowerment pertain to elderly populations. The proposed study will evaluate the impact of a three-session SDM nursing intervention among depressed elderly primary care patients, in comparison to Usual Care (UC), on patient adherence to antidepressant medication or psychotherapy and on reduction in depressive symptoms. The focus of the SDM intervention is to empower elderly depressed primary care patients and help them efficiently arrive at a treatment decision that can be successfully implemented. Based on our prior work that demonstrated the impact of patients´ a priori treatment preferences on treatment initiation and adherence, we propose to conduct a randomized controlled trial of elderly depressed primary care patients to determine the impact of SDM on treatment adherence and reduction in depressive symptoms. The study randomizes 30 physicians from Lincoln Hospital in the Bronx, a large ethnically diverse primary care clinic, to either Shared Decision-Making (SDM) or the Usual Care (UC) comparison condition. A total of 210 depressed (PHQ-9>15) geriatric patients whose physicians´ recommend starting depression treatment, will receive either SDM or UC according to physician randomization. Subjects will be assessed at baseline and at weeks 4, 8, 12, and 24 to determine treatment adherence and depressive status. If SDM is effective, it may serve as a brief independent intervention by practice nurses, and will provide a platform to tailor and disseminate the model throughout a variety of primary care practice settings and populations. Shared decision-making, in contrast to traditional medical decision-making, involves a collaborative process whereby patients share personal values and preferences and clinicians provide information to arrive at a mutually-agreed upon treatment decision. The proposed study will evaluate the impact of a shared decision- making nursing intervention among depressed elderly primary care patients on patient adherence to depression treatment and on improvement in depression. The focus of the intervention is to empower elderly depressed primary care patients and help them efficiently arrive at a treatment decision that they can successfully implement
Keywords: active method; Acute; Address; Adherence (attribute); Age; age group; Aged, 80 and over; Alcohol abuse; Antidepressive Agents; base; Belief; Caring; Characteristics; Clinic; Clinical; Clinical Research; Compliance behavior; Computerized Medical Record; Data; Decision Making; Depressed mood; depressive symptoms; Diagnosis; Disease; Disease remission; DSM-IV; Effectiveness; Elderly; Eligibility Determination; empowered; empowerment; Exhibits; expectation; Family; Feeling hopeless; follow-up; Goals; group intervention; Hamilton Rating Scale for Depression; Health; Health behavior change; Hospitals; Human Resources; Impaired cognition; improved; indexing; Individual; innovation; Intention; Intervention; Interview; Knowledge; Malignant Neoplasms; Measures; Mediating; Mediator of activation protein; Medical; meetings; Mental Depression; Mental disorders; Mental Health; mental state; Modeling; National Institute of Mental Health (U.S.); Nature; New York City; NIH Program Announcements; Nurses; nursing intervention; Outcome; patient oriented; Patients; Personality Traits; Persons; Pharmaceutical Preparations; Physicians; Population; preference; Primary Care Physician; Primary Health Care; Process; Psychiatric therapeutic procedure; Psychotherapy; public health relevance; Randomized; Randomized Controlled Trials; Recruitment Activity; Research; Role; satisfaction; Screening procedure; Severities; shared decision making; Solo Practices; Staging; standard care; Structure; Substance abuse problem; Suicide; Symptoms; Telephone; Testing; theories; Training; treatment adherence; treatment as usual; Treatment Cost; Treatment outcome; Trust; Uncertainty; Visit; Work
Relevance: Shared decision-making, in contrast to traditional medical decision-making, involves a collaborative process whereby patients sharee personal values and preferences and clinicians provide information to arrive at a mutually-agreed upon treatment decision. The proposed study will evaluate the impact of a shared decision- making nursing intervention among depressed elderly primary care patients on patient adherence to depression treatment and on improvement in depression. The focus of the intervention is to empower elderly depressed primary care patients and help them efficiently arrive at a treatment decision that they can successfully implement
Project start date: 2009-07-17
Project end date: 2014-02-28
Budget start date: 1-MAY-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-07-163
5R01MH084872-03 (2011): $353317
FUNCTIONAL CHARACTERIZATION OF THE SCHISTOSOME TEGUMENT
J Patrick, Associate Professor
Tufts University Bostoncity: Boston country: United States (us)
Grant 5R01AI056273-07 from National Institute Of Allergy And Infectious Diseases
Abstract: Schistosomes are parasitic flatworms that cause a chronic, debilitating disease afflicting over 200 million people in over 70 countries. The parasites live for years, sometimes decades, in what should be a very hostile environment - the blood of vertebrates - yet they appear to solicit little if any protective reaction from two of the host´s major defensive systems the hemostatic system and the immune system. We hypothesize that proteins at the host-interactive surface are central to the parasites ability to dampen host immunity and hemostasis while, at the same time, permitting metabolite exchange. In this competing renewal, we propose to use new molecular methods such as RNA interference that were first developed for use with schistosomes under our previous grant, RO1 AI056273, to test several key hypotheses concerning 1) the role of tegumental ecto-enzymes in hemostasis and immunomodulation, 2) the ability of tegumental sphingomyelinase to alter permeability properties at the parasite surface, and 3) the molecular mechanisms of trans- tegumental metabolite exchange. The functional genomics approach we adopt here coupled with independent and direct, follow-up experiments employing more traditional cell biology and biochemistry techniques are designed to provide significant new information concerning the schistosome host interactive surface. In addition the work is designed to identify tegumental proteins critical for parasite survival in the host and subsequent screens will be undertaken to discover drugs that inhibit these molecules. In this way, our planned experiments have the potential to reveal novel and valid targets, as well as new treatments, for intervention in a parasite that remains a widespread and major cause of human disease. Schistosomes are parasite worms that live in the blood streams of over 200 million people in more than 70 countries. These parasites are a major cause of death and disability worldwide. The worms have remarkable properties that allow them live inside people for many years. These properties include an ability to block our immune responses from targeting them, an ability to take in nutrients from our blood and an ability to detect environmental stresses and respond appropriately. By understanding more precisely how the parasites achieve these ends, we aim to block these capabilities and kill the worms
Keywords: Adenosine; Adopted; Alkaline Phosphatase; analog; Applications Grants; Attenuated; Back; Biochemical; Biochemistry; Blood; Cause of Death; Cells; Cellular biology; Chronic; Cleaved cell; comparative; Complex; Country; Coupled; Data; design; disability; Disease; ectoADPase; Environment; Enzymes; follow-up; functional genomics; Gene Expression; Genes; Gold; Grant; Hemostatic Agents; Hemostatic function; human disease; Immune; Immune response; Immune system; Immunity; immunoregulation; improved; In Vitro; in vivo; Inflammation; Inflammatory; Intervention; Killings; Knowledge; Life; Measures; Mediating; Mediator of activation protein; Membrane; Metabolic; Methods; Molecular; Monitor; Movement; novel; Nucleotides; Nutrient; Parasite Control; Parasites; Permeability; Pharmaceutical Preparations; Phospholipids; phosphoric diester hydrolase; Pichia; Platelet Activating Factor; Platyhelminths; Praziquantel; Predisposition; Property; Proteins; public health relevance; purine; Purines; Pyrimidine; Pyrimidines; Reaction; Recombinant Proteins; Recombinants; Relative (related person); research study; response; RNA Interference; Role; Schistosoma; Schistosome Parasite; Schistosomiasis; Signal Transduction; Signaling Molecule; Site; Sphingomyelinase; Stream; Stress; Surface; System; Techniques; Testing; Time; uptake; Vertebrates; wasting; Water; water channel; Work
Relevance: Schistosomes are parasite worms that live in the blood streams of over 200 million people in more than 70 countries. These parasites are a major cause of death and disability worldwide. The worms have remarkable properties that allow them live inside people for many years. These properties include an ability to block our immune responses from targeting them, an ability to take in nutrients from our blood and an ability to detect environmental stresses and respond appropriately. By understanding more precisely how the parasites achieve these ends, we aim to block these capabilities and kill the worms
Project start date: 2003-06-01
Project end date: 2015-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01AI056273-07 (2011): $408375
Sponsored Links Excellgen http://Excellgen.com
CHRONIC ETHANOL AND SK2 POTASSIUM CHANNELS
J Patrick, Assistant Professor
Medical University Of South Carolinacity: Charleston country: United States (us)
Grant 5R00AA017922-03 from National Institute On Alcohol Abuse And Alcoholism
Abstract: Recent evidence suggests that ethanol-associated homeostatic plasticity involves compensatory increases in synaptic NMDA receptors that contributes to aberrant hyperexcitability upon cessation of consumption and may underlie craving that leads to the high incidence of relapse in alcohol dependent individuals. Small-conductance calcium-activated potassium (SK) channels regulate NMDA receptor-dependent calcium influx and are critical modulators of hippocampal-dependent synaptic plasticity. This is consistent with the suggestion that SK2 channels and NMDA receptors form a regulatory calcium-mediated feedback loop within individual dendritic spines. Preliminary evidence demonstrates a reduction in surface SK2 channels following chronic ethanol treatment that leads to a disruption of the SK channel-NMDA receptor feedback loop. Moreover, we have demonstrated that modulation of SK channels can influence voluntary drinking behavior. Thus, the overarching hypothesis is that SK2 channels contribute to alcohol-associated plasticity of glutamatergic synapses and that positive modulation of SK channels reduces the severity of withdrawal-related hyperexcitability and decreases alcohol intake. These studies will test the hypotheses that 1) chronic ethanol exposure produces a homeostatic reduction in SK2 channel expression through PKA signaling, 2) modulation of the SK channel-NMDA receptor feedback loop can reduce ethanol withdrawal , hyperexcitability and neurotoxicity, and 3) modulation of the synaptic feedback loop will reduce voluntary alcohol consumption. Decreases in SK2 channels and increases in NMDA receptors may represent a common homeostatic adaptive response to prolonged reductions in NMDA receptor activity during ethanol exposure. Furthermore, this functional uncoupling of the SK2 channel-NMDA receptor calcium-mediated feedback loop may contribute to tolerance development and to withdrawal hyperexcitability
Keywords: Alcohol consumption; Alcohol dependence; alcohol exposure; Alcohol withdrawal syndrome; Alcohols; Award; Calcium; Chronic; Consumption; craving; Cyclic AMP-Dependent Protein Kinases; Dendritic Spines; Development; drinking behavior; Ethanol; Feedback; Glutamates; Hippocampus (Brain); Incidence; Individual; insight; Mediating; N-Methyl-D-Aspartate Receptors; neurotoxicity; new therapeutic target; Potassium Channel; Relapse; response; Severities; Signal Transduction; SK potassium channel; Suggestion; Surface; Synapses; Synaptic plasticity; Testing; Withdrawal
Project start date: 2009-07-10
Project end date: 2013-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5R00AA017922-03 (2011): $187950
INACTIVITY AND ENHANCED SYMPATHOEXCITATION: ROLE OF NEUROPLASTICITY IN THE RVLM
J Patrick, Assistant Professor
Wayne State Universitycity: Detroit country: United States (us)
Grant 5R01HL096787-02 from National Heart, Lung, And Blood Institute
Abstract: Physical inactivity is a major independent risk factor for cardiovascular disease (CVD) and is now considered one of the leading contributors to premature death (Blair, 2009). Rates of physical inactivity continue to increase along with health care costs to treat CVD. Despite these disturbing trends, the mechanisms by which a sedentary lifestyle leads to CVD are not fully known. CVD is associated with increased sympathetic nervous system activity and overactivity of a brainstem region known as the rostral ventrolateral medulla (RVLM) (Sved et al., 2003; Guyenet, 2006). Sympathoexcitatory responses to direct activation of the RVLM are enhanced in sedentary versus physically active animals (Mueller, 2007). These data suggest that a sedentary lifestyle may contribute to the development of CVD by increased sensitivity of RVLM neurons. Our long term goal is to understand the central sympathetic mechanisms by which physical inactivity contributes to the development of CVD. This is an important clinical, economic and public health care problem. The overall objective of this application is to determine mechanisms by which physical inactivity (versus physical activity) increases sympathetic output from neurons in the RVLM. The central hypothesis is that enhanced sympathoexcitation observed in sedentary animals is due to increased NMDA receptor-mediated excitation of RVLM neurons that regulate sympathetic activity to functional distinct organs involved in blood pressure regulation. We plan to test our central hypothesis and accomplish the overall objectives of this application by pursuing the following specific aims 1) Determine the extent to which sedentary versus physically active conditions alter reflex sympathoexcitation to functionally distinct target organs involved in blood pressure regulation. 2) Examine the effect of sedentary versus physically active conditions on activation of spinally-projecting sympathoexcitatory neurons of the RVLM. 3) Ascertain the mechanisms by which NMDA receptor mediated transmission in the RVLM may enhance sympathoexcitation in sedentary versus physically active rats. Our proposal provides a compelling rationale to understand the mechanisms by which a sedentary lifestyle may predispose individuals to CVD. We expect to establish at the end of this five year project the extent to which physical inactivity impacts regulation of a group of neurons that are critical to normal and pathophysiological increases in sympathetic nervous system activity. The results of this proposal will provide a greater understanding of the detrimental effects of a sedentary lifestyle on cardiovascular health and define potential therapeutic targets for the treatment and prevention of CVD. These studies may improve the lives of individuals who are unable or unwilling to exercise by 1) the development of new treatment options for CVD; 2) increasing public awareness of the detrimental effects of a sedentary lifestyle; and 3) indirectly reducing escalating health care costs associated with physical inactivity. The proposed research is relevant to public health because a sedentary lifestyle is a major risk factor for cardiovascular disease and is now considered the number one cause of preventable death. This proposal examines an important group of neurons within the brain that we propose contribute to the increased incidence of cardiovascular disease in sedentary individuals. This contribution is significant because it is expected to provide knowledge that could be used to develop therapeutic strategies that will counteract the effects of a sedentary lifestyle on cardiovascular diseases that are currently burdening the population and our health care system
Keywords: Acute; Adrenal Glands; Affect; Animals; aspartate receptor; Awareness; blood pressure regulation; Brain; Brain region; Brain Stem; Cardiovascular Diseases; cardiovascular disorder prevention; cardiovascular disorder risk; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Clinical; Cognition; Data; Development; Economics; Exercise; Exhibits; Functional disorder; Glutamates; Goals; Health; Health Care Costs; Healthcare; Healthcare Systems; Hippocampus (Brain); improved; Incidence; Individual; Kidney; Knowledge; Laboratories; Life Style; Link; Mediating; Memory; N-Methylaspartate; Nerve; Neuronal Plasticity; Neurons; NIH Program Announcements; Organ; Outcome; Output; Phosphorylation; Physical activity; Population; premature; Prevention; public health medicine (field); public health relevance; Rattus; receptor expression; Reflex action; Regulation; Research; response; Risk Factors; Role; sedentary; Sympathetic Nervous System; Testing; Therapeutic; therapeutic target; Time; transmission process; trend; Vasoconstrictor Agents; Vasodilator Agents; Work
Relevance: The proposed research is relevant to public health because a sedentary lifestyle is a major risk factor for cardiovascular disease and is now considered the number one cause of preventable death. This proposal examines an important group of neurons within the brain that we propose contribute to the increased incidence of cardiovascular disease in sedentary individuals. This contribution is significant because it is expected to provide knowledge that could be used to develop therapeutic strategies that will counteract the effects of a sedentary lifestyle on cardiovascular diseases that are currently burdening the population and our health care system
Project start date: 2010-08-01
Project end date: 2014-05-31
Budget start date: 1-AUG-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-09-243
5R01HL096787-02 (2011): $380000
3R01HL096787-02S1 (2011): $52451
REACTIVE OXYGEN SPECIES IN VASCULAR DISEASE
J Patrick, Professor
University Of Pittsburgh At Pittsburghcity: Pittsburgh country: United States (us)
Grant 5R01HL079207-06 from National Heart, Lung, And Blood Institute
Abstract: NAD(P)H oxidases are broadly activated in cardiovascular diseases, including hypertension, atherosclerosis, and diabetes. Reactive oxygen species (ROS) derived from these oxidases have been implicated in impaired vascular relaxation, medial hypertrophy, and neointimal hyperplasia in various forms of hypertension. NAD(P)H oxidase-derived superoxide anion (O2-) and other ROS are believed to mediate stretch-induced signaling, leading to neointimal hyperplasia. We previously developed a cell-permeant inhibitor of gp91-phox- (nox2-) based oxidase assembly which is capable of abrogating vascular O2- production in response to angiotensin II. The current proposal stems from 3 major findings, demonstrating (a) the importance of the multi-component oxidase assembly in vascular O2- production; (b) the ability of our cell-permeant inhibitor of nox2-based oxidase assembly to inhibit O2- and attenuate neointimal proliferation of the rat carotid artery in response to balloon angioplasty; and (c) the upregulation of novel nox2 homologues, nox1 and nox4, in response to balloon injury. Since nox1 and nox4 appear to be important oxidase homologues involved differentially in vascular O2- production after stretch, we will determine the efficacy of docking sequence mimics (which inhibit nox1and nox4 assembly with other oxidase subunits) to inhibit whole-vessel and endothelial, smooth muscle cell and fibroblast O2- generation and neointimal proliferation. These studies will address the hypothesis that nox1 and nox4 are functionally involved in vascular stretch-induced oxidase assembly and O2- generation, leading to neointimal proliferation. Three specific aims will be tested (1) to develop specific inhibitors of nox1- and nox4-based oxidases and test them in an in vitro model of hormone-induced vascular NAD(P)H oxidase activation; (2) to investigate the role of docking sequences on individual nox-based oxidases in vascular stretch-induced oxidase activity in vitro; and (3) to determine the role of nox docking sequences in balloon angioplasty-induced neointimal hyperplasia in vivo. Relevance Therapies aimed at disrupting the various NAD(P)H oxidase systems in blood vessels should substantially improve vascular patency and function following balloon angioplasty. These inhibitors are also expected to provide broad utility in a variety of disease processes involving oxidants, including hypertension, diabetes and atherosclerosis
Keywords: 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; Abbreviations; Address; alpha-Thrombin; Amino Acids; Angioplasty; Angiotensin II; Atherosclerosis; Attenuated; Balloon Angioplasty; base; Binding (Molecular Function); Biological Assay; Blood Vessels; Cardiovascular Diseases; Carotid Arteries; Catalytic Domain; Cells; Chimeric Proteins; cofactor; Common carotid artery; comparative efficacy; Data; Diabetes Mellitus; digital; diphenyleneiodonium; Disease; Docking; Dose; Effectiveness; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Enzymes; Fatty acid glycerol esters; Fibroblasts; Generations; Growth; HIV; Homologous Gene; Hormones; human CYBA protein; Hydrogen Peroxide; Hyperplasia; Hypertension; Hypertrophy; improved; In Vitro; in vitro activity; in vitro Model; in vivo; Individual; Infusion procedures; inhibitor/antagonist; Inhibitory Concentration 50; Injury; Lead; Literature; Medial; Mediating; Membrane; Modeling; morphometry; NADH; NADP; NADPH Oxidase; Names; neutrophil cytosol factor 67K; Nitric Oxide; novel; Oxidants; Oxidases; Peptides; Phagocytes; Play; prevent; Process; Production; Protein Isoforms; prototype; Rattus; Reactive Oxygen Species; Relative (related person); Relaxation; Research Personnel; research study; response; response to injury; Role; Signal Transduction; Smooth Muscle Myocytes; stem; Stretching; Superoxide Dismutase; superoxide-generating NADPH oxidase; Superoxides; System; Testing; Thrombin; Tumor Necrosis Factor-alpha; Up-Regulation (Physiology); Vascular Diseases; Vascular Patency
Project start date: 2007-04-01
Project end date: 2012-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
5R01HL079207-06 (2011): $373226
STATISTICAL METHODS FOR LONGITUDINAL STUDIES
J Patrick, Professor
University Of Washingtoncity: Seattle country: United States (us)
Grant 2R01HL072966-05A1 from National Heart, Lung, And Blood Institute
Abstract: Longitudinal studies in medicine are faced with new analysis challenges due to continually advancing measurement and database technologies. Specifically, innovations in molecular assays, medical imaging, and psychological assessment have generated numerous new putative markers of disease progression. Also, advances in electronic data recording now allow longitudinal investigations to collect observational data measuring changes in outcomes and changes in treatments where dynamic treatment covariates are driven by current clinical guidelines, by unfolding patient health characteristics, or other factors. The overall goals of this proposal are to develop statistical methodology and software tools for analyzing modern longitudinal biomedical data. The specific areas of emphasis are 1. Repeated measures and time-dependent accuracy. Biomarkers are measurements that characterize specific aspects of patient health status. This aim will develop semi-parametric and non-parametric statistical methods to estimate the ability of prognostic scores or markers to accurately predict event times as characterized by time-dependent measures of sensitivity and specificity. 2. Observational longitudinal data and time-dependent exposure. Longitudinal studies now routinely collect both patient health information and changing covariate (treatment, exposure) data. This aim will develop statistical methods that can be used to estimate causal effects of exposure, and to evaluate the ability of marker values to guide the choice or timing of treatment. In this proposal, we will develop new statistical methods for the analysis of longitudinal data. In particular, we will develop methods that can evaluate the time-dependent sensitivity and specificity of a biomarker for the prediction of future event times such as disease onset or death. In addition, we will evaluate and develop methods for the analysis of observational longitudinal data commonly recorded in electronic medical records where both measures of health status and measures of treatment change over time. We will focus research on estimation of the causal effect of treatments that are modified over time, and on the estimation of the ability of biomarkers to be used to guide the choice of which subjects are likely to obtain the largest benefit from specific treatment options
Keywords: Area; Area Under Curve; base; Biological Assay; biomarker; case control; Cessation of life; Characteristics; Classification; Clinical; Computer software; Computerized Medical Record; Data; Data Analyses; Databases; Development; Disease; Disease Progression; electronic data; Evaluation; Event; Exposure to; Foundations; Funding; Future; Goals; Guidelines; Health; Health Status; innovation; Investigation; longitudinal analysis; Longitudinal Studies; Measurement; Measures; Medical Imaging; Medicine; Methodology; Methods; Modeling; Molecular; Onset of illness; open source; Outcome; Patients; prognostic; Prognostic Marker; psychologic; Receiver Operating Characteristics; Research; Risk; Selection for Treatments; Sensitivity and Specificity; Software Tools; Specificity; Statistical Methods; stem; Structural Models; Technology; Technology Transfer; theories; Time; treatment effect; user-friendly
Relevance: In this proposal, we will develop new statistical methods for the analysis of longitudinal data. In particular, we will develop methods that can evaluate the time-dependent sensitivity and specificity of a biomarker for the prediction of future event times such as disease onset or death. In addition, we will evaluate and develop methods for the analysis of observational longitudinal data commonly recorded in electronic medical records where both measures of health status and measures of treatment change over time. We will focus research on estimation of the causal effect of treatments that are modified over time, and on the estimation of the ability of biomarkers to be used to guide the choice of which subjects are likely to obtain the largest benefit from specific treatment options
Project start date: 2003-04-25
Project end date: 2015-06-30
Budget start date: 15-AUG-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-10-067
2R01HL072966-05A1 (2011): $293150
INTERNALIZING PATHWAYS TO DRUG USE: A MULTI-SAMPLE ANALYSIS
J Patrick, Professor
University Of North Carolina Chapel Hillcity: Chapel Hill country: United States (us)
Grant 5R01DA015398-07 from National Institute On Drug Abuse
Abstract: In this application, we evaluate an internalizing pathway to substance use disorders (SUDs) and consider the etiology of Negative Affect SUDs, a potential phenotype of SUDs identifiable by comorbidity with disorders involving negative affect (i.e., depression and anxiety). We conduct an integrative (secondary) analysis (refined in our prior project period) involving the simultaneous analysis of three nationally prominent longitudinal studies of children of alcoholic parents and matched controls that collectively span the first four decades of life (ages 2 through 38). Understanding developmental pathways leading to SUDs is critical in efforts to design and implement effective intervention and treatment programs for youth. Although behavioral indicators of risk for adolescent substance involvement appear as early as 2-5 years of age, few theories about developmental pathways to SUDs consider risk processes that begin in the preschool years. Moreover, few studies are capable of evaluating theories about these developmental pathways. Longitudinal studies that span the first four decades of life, when SUDs emerge, peak and begin to decline, are rare. Available cohort- or population-based studies often yield too few cases to disentangle different pathways for SUDs. Thus, long-term, longitudinal studies of high-risk populations, such as children of alcoholic parents, are invaluable for articulating developmental pathways to SUDs. Using this method, we pursue five specific aims (1) to define and test an internalizing pathway to SUDs and to evaluate whether evidence supports heterotypic continuity (i.e., different developmental expressions of a single underlying trait) of Negative Affect SUDs over time, (2) to examine the developmentally-varying unique, mediated and interactive effects of internalizing and externalizing processes as predictors of substance involvement and Negative Affect SUDs across the first four decades of life, (3) to examine gender, parental depressive alcoholism, and contextual factors as important moderators of progression along an internalizing pathway toward Negative Affect SUDs as a function of developmental timing, (4) to examine whether the predictive utility of an internalizing model differs over various substances used in isolation (i.e., alcohol, tobacco, marijuana, stimulant and depressant drug) or in combination with one another, and (5) to develop methods for integrative analysis, to utilize these methods to test Aims 1-4, and to disseminate these methods to other applied researchers. Our application tests an internalizing pathway to substance use disorder over the first four decades of life. Studies of such early emerging but persistent pathways are rare but critical to efforts to design and implement effective intervention and treatment programs for youth
Keywords: 0-11 years old; 12-20 years old; 21+ years old; 5 year old; Adolescence; adolescence (12-20); Adolescent; Adolescent Youth; Adult; adult human (21+); adult youth; Affect; Age; age difference; aged; Alcohol or Other Drugs use; Alcoholic; Alcoholism; Alcohols; anti social; antisocial; Anxiety; AOD use; Application Context; Archives; Behavioral; Boozer; Causality; Chemical Class, Alcohol; Child; Child Youth; Childhood; children; Children (0-21); children of alcoholics; Cognitive; cohort; college; Comorbidity; contextual factors; Data; Data Set; Dataset; Deceleration; Dependent drinker; depressed; Depressed mood; Depression; depressive; depressive symptoms; design; designing; Development; Disease; disease causation; disease etiology; disease/disorder; disease/disorder etiology; Disorder; disorder etiology; Drug usage; drug use; drug/agent; Drugs; effective intervention; effective therapy; emerging adult; Emotional Depression; Etiology; experience; Family; five year old; Gender; Goals; Health behavior; high risk; high school; Human, Adult; Human, Child; Interview; Investigators; juvenile; juvenile human; Life; Literature; long-term study; Longitudinal Studies; Marihuana; Mediating; Medication; Mental Depression; Methods; Michigan; Modeling; novel; Nursery Schools; Outcome; Parents; Participant; pathway; Pathway interactions; Pattern; pediatric; Pharmaceutic Preparations; Pharmaceutical Preparations; Phenotype; Population; population based; Prevention; Prevention program; Prevention strategy; Preventive strategy; problem drinker; Process; public health relevance; Research Personnel; Researchers; Risk; Risk Factors; sadness; Sampling; Sampling Studies; Self Medication; social; Statistical Methods; stressor; SUBGP; Subgroup; substance use; Substance Use Disorder; Survey Instrument; Surveys; Symptoms; Symptoms of depression; teenage; Temperament; Testing; theories; Time; Tobacco; trait; treatment program; Wood; Wood material; young adult; youngster; Youth; Youth 10-21
Relevance: Our proposal tests an internalizing pathway to substance use disorder over the first four decades of life. Studies of such early emerging but persistent pathways are rare but critical to efforts to design and implement effective intervention and treatment programs for youth
Project start date: 2002-08-15
Project end date: 2012-11-30
Budget start date: 1-DEC-2010
Budget end date: 30-NOV-2011
PFA/PA: PA-07-082
5R01DA015398-07 (2011): $330048
3R01DA015398-07S1 (2011): $45489
MEASUREMENT MODELS IN LATENT CURVE ANALYSIS
J Patrick
University Of North Carolina Chapel Hillcity: Chapel Hill country: United States (us)
Grant 5R01DA013148-08 from National Institute On Drug Abuse
Abstract: In our first project period we focused on the systematic study of longitudinal latent curve models (LCMs) applied to continuous scale scores with a particular emphasis on challenges that commonly arise in the empirical study of substance use. Despite the many advantages of these LCMs, one limitation is that methods are currently not well developed to fit LCMs to repeated measures that are ordinally scaled, particularly in the presence of missing data. A second limitation stems from the potential violation of a strict set of required assumptions governing the structure of the measurement model of continuous or ordinally observed scale scores over time. To address these limitations, we have drawn upon our findings from the initial project period and have designed the revision of our proposed continuation project around the systematic study of measurement models in latent curve analysis. Our proposed project is organized around four specific aims. In Aim 1 we propose to study existing challenges and identify optimal strategies for fitting LCMs to ordinal manifest scale scores assessed overtime both with complete and missing data. In Aim 2 we plan to study the incorporation of latent factors with continuously scaled indicators in LCMs to allow for tests of measurement invariance and the inclusion of formal measurement models. In Aim 3 we propose extending the findings of Aim 2 to include the incorporation of latent factors with ordinally scaled indicators in LCMs. Finally, in Aim 4 we plan to study the implications of item scaling and measurement invariance across all prior aims with respect to the estimation of statistical power and optimal study design. These project goals will be pursued through the integrated use of analytical review and organization, computer simulation studies, and the analysis of data drawn from an existing longitudinal study of the parental alcoholism effects on the development of drug use in a large sample of adolescent. Taken together, we believe the proposed study has the potential for making significant unique contributions to the field of quantitative methodology and to the rigorous empirical study of developmental trajectories of substance use and abuse
Keywords: Address; Adolescent; adolescent substance use; Adolescent Youth; Alcohol or Other Drugs use; Alcoholism; Analysis, Data; AOD use; base; Behavioral Sciences; Book Chapters; Class; Classification; Complex; computational modeling; computational models; computational simulation; computer based models; computer program/software; Computer Programs; Computer Simulation; Computer software; computerized modeling; Computerized Models; computerized simulation; Condition; conference; Data; Data Analyses; Data Set; Dataset; design; designing; Development; Drug usage; drug use; Evaluation; Experimental Designs; Future; Goals; Guidelines; in silico; Investigators; juvenile; juvenile human; Knowledge; long-term study; Longitudinal Studies; Mathematical Model Simulation; Mathematical Models and Simulations; Measurement; Measures; Method LOINC Axis 6; Methodology; Methods; Metric; Modeling; Models, Computer; Numbers; Outcome; Paper; Peer Review; Personal Satisfaction; post-doctoral training; postdoctoral training; programs; Programs (PT); Programs [Publication Type]; Publications; Recommendation; Research; Research Design; Research Personnel; Researchers; Role; Sampling; Scientific Publication; Score; Simulation, Computer based; social role; Software; Standards; Standards of Weights and Measures; stem; Structure; study design; Study Type; substance use; Sum; symposium; Systematics; Testing; Time; virtual simulation; well-being; youth substance use
Project start date: 1999-07-01
Project end date: 2011-04-30
Budget start date: 1-MAY-2008
Budget end date: 30-APR-2011
PFA/PA: PA-02-072
5R01DA013148-08 (2008): $266714
VALIDATION OF AN IN VITRO HUMAN AIRWAY MODEL
J Patrick, Senior Scientist
Mattek Corporationcity: Ashland country: United States (us)
Grant 2R44ES014312-02 from National Institute Of Environmental Health Sciences
Abstract: Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. Recently enacted legislation including the European Union (EU) Registration, Labeling and Authorization of Chemicals (REACH) program, and the US EPA High production Volume (HPV) Chemical Challenge will dramatically increase the need for inhalation toxicity information. The goal of the present grant proposal is to validate the EpiAirway in vitro human airway model for prediction of in vivo human inhalation toxicity hazard potential following Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Center for Validation of Alternative Methods (ECVAM) guidelines. Phase I experiments produced several prediction models that will be further tested in the current Phase II project. One hundred chemicals that have available in vivo human or animal inhalation toxicity data and established immediately Dangerous to Life or health (IDLH) concentrations established by NIOSH will be utilized in the Phase II validation project. Interlaboratory transferability of the method will also be evaluated in 4 laboratories using a subset of 30 chemicals chosen from the original 100 tested during the Phase II study. The study data will then be submitted for independent statistical analysis and the final results and report will be submitted to regulatory agencies (i.e. ICCVAM) in support of regulatory acceptance. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and a technical capacity that is urgently needed but that does not presently exist. The methodology developed will provide a transformative technology that will facilitate the paradigm shift from in vivo rodent to in vitro human inhalation toxicology testing envisioned in the resent National Research Council Report "Toxicity Testing in the 21st Century A Vision and a Strategy". Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and provide a technical capability that is urgently needed but that does not presently exist
Keywords: Acute; Address; Animals; Applications Grants; Aspiration, Respiratory; Assay; Authorization; Authorization documentation; Bioassay; Biologic Assays; Biological Assay; Breathing; Chemicals; Commerce; Commerces; consumer product; Contracting Opportunities; Contracts; Data; Data Set; Dataset; Emergencies; Emergency Situation; Equation; European; European Community; European Union; Evaluation; experiment; experimental research; experimental study; Goals; Government; Grant Proposals; Grants, Applications; Guidelines; hazard; Hazard Assessment; Hazardous Chemicals; Health; Human; Human, General; In Vitro; in vivo; Industry; Inhalation; Inhalation Toxicology; Inhaling; inspiration; Inspiration, Respiratory; Institutes; Interagency Coordinating Committee on the Validation of Alternative Methods; International; irritation; Jobs; Label; Laboratories; Legislation; Letters; Life; Mammals, Rodents; Man (Taxonomy); Man, Modern; Manufacturer; Manufacturer Name; Method LOINC Axis 6; Methodology; Methods; Modeling; National Research Council; National Research Council (U.S.); Occupations; Permission; Phase; phase 2 study; Procedures; Production; Professional Postions; programs; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; public health relevance; Regulation; Reporting; Research; research study; respiratory; response; Rodent; Rodentia; Rodentias; Safety; Services; Sight; Statutes and Laws; success; Technology; Testing; Toxic effect; Toxicities; Toxicity Testing; Toxicity Tests; Validation; validation studies; Vision
Project start date: 2011-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-10-050
2R44ES014312-02 (2011): $298491
GENE-NUTRIENT INTERACTIONS IN NEURAL TUBE DEFECTS
J Patrick, Associate Professor
Cornell University Ithacacity: Ithaca country: United States (us)
Grant 5R01HD059120-04 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Folate metabolism is required for the synthesis of nucleotides (purines and dTMP) and S- adenosylmethionine (AdoMet). Disruption of folate metabolism affects AdoMet and dTMP syntheses and thereby influences AdoMet-dependent methylation reactions and uracil content in DNA. Both DNA uracil and methylation affect DNA stability, and chromatin methylation regulates the expression of many genes. It is not known if the associations between disruptions in folate metabolism and pathologies (including certain cancers, cardiovascular disease) and developmental anomalies (including neural tube defects (NTDs)) result from altered AdoMet synthesis and/or dTMP synthesis. Recently, we demonstrated that the enzyme cytoplasmic serine hydroxymethyltransferase (cSHMT) is a metabolic switch that regulates the flux of folate-activated one-carbon units between the dTMP and AdoMet biosynthetic pathways. Reduced expression of cSHMT, as observed in both cSHMT and cSHMT-/- mice, induces embryonic NTDs, sensitizes the animals to colon cancer, affects uracil content in DNA and increases the AdoMet/AdoHcy ratio. This is the only mouse model to exhibit NTDs as a result of the disruption of a folate-dependent enzyme, and thereby enables elucidation of the mechanisms underlying folate-responsive NTDs. CSHMT is expressed in tissues known to be associated with folate-related pathologies/developmental anomalies including NTDs. The expression and activity of cSHMT is dynamically regulated by several nutrients and therefore the cSHMT has the potential to contribute to the etiology of folate-related pathologies and may be a target for prevention through diet. The contributions of diet, embryonic and maternal cSHMT genotype to NTD occurrence will be determined, and the metabolic role of cSHMT in NTD etiology will be elucidated. The specific aims are 1) to determine the gene-nutrient interactions that increase risk for NTDs in mice deficient in cSHMT. 2) to determine the metabolic defect associated with neural tube closure defects. 3) to elucidate the contribution of cSHMT SUMOylation to NTD frequency. 4) to determine if cSHMT and MTHFR interact to increase risk for folate-responsive NTDs. The principle hypotheses to be tested are that 1) cSHMT expression contributes to folate-responsive NTD risk by altering folate metabolism. 2) impairments in cSHMT SUMOylation affect dTMP and AdoMet synthesis and risk for NTDs. 3) the cSHMT and MTHFR genes interact to increase risk for folate-responsive NTDs. The long-term goals of this project is to determine the mechanisms underlying neural tube closure defects and the role of cSHMT in NTD prevention. Folate-related pathologies, including certain cancers, and developmental defects, including neural tube defects, are common and complex disorders involving gene nutrient interactions but the underlying mechanisms are not established. Folate-fortification of the US food supply was implemented to reduce incidence of birth defects, yet concerns remain regarding the effects of folate fortification on cancer incidence. The studies outlined in this proposal will investigate the mechanisms of folate-related birth defects and role of folate and other dietary components in preventing these defects in the first mouse model of folate-related birth defects resulting from disrupted folate metabolism
Keywords: Affect; Animal Model; Animals; Carbon; Cardiovascular Diseases; Choline; Chromatin; Cleft Palate; Colon Carcinoma; Complex; Congenital Abnormality; Crown rump length; Data; Defect; Development; Diet; Dietary Component; Disease; DNA; DNA glycosylase; DNA Maintenance; Embryo; Enzymes; Etiology; Exhibits; Ferritin; Folate; folic acid metabolism; Food Interactions; Food Supply; fortification; Frequencies (time pattern); Genes; Genetic; Genotype; Glycine Hydroxymethyltransferase; Goals; Health; Homocysteine; Homocystine; Human; Impairment; Incidence; Iron; Knockout Mice; Liver; male; Malignant Neoplasms; Malignant Palate Neoplasm; Measures; Mediating; Metabolic; Metabolism; Methionine; Methylation; Modeling; mouse model; MTHFR gene; Mus; Neural Tube Closure; Neural Tube Defects; Nuclear; Nucleotide Biosynthesis; nucleotide metabolism; Nutrient; Partner in relationship; Pathology; Pathway interactions; prevent; Prevention; purine; Purine Nucleotides; Purines; Reaction; Relative (related person); Risk; Role; S-Adenosylmethionine; Single Nucleotide Polymorphism; Supplementation; Testing; Thymidine; Tissues; Tretinoin; Ubiquitination; Uracil; Vitamin B6; Vitamin Deficiency; Weaning
Project start date: 2008-09-25
Project end date: 2013-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-07-070
5R01HD059120-04 (2011): $311018
Sponsored Links Excellgen http://Excellgen.com
HAZARDOUS WASTE WORKER TRAINING PROGRAM (HWWTP)
J Patrick
International Association Fire Fighterscity: Washington country: United States (us)
Abstract: Fire departments provide invaluable services to communities nationwide. They respond to all emergency situations. They also respond to mergency service calls and good intent calls. Often what is described to dispatchers does not reflect the actual incident. Nevertheless, fire departments are trained and prepared to respond to a broad array of situations. While "fire" is part of the department name, less than 10 percent of runs made by fire departments actually involve fire.´ The United States Department of Transportation (DOT) reports 170,527 hazardous materials incidents resulting in 2,857 injuries and 137 fatalities from 1999 to 2008.´´ An estimated 36 percent of fire departments involved in hazardous material response have formal training in those duties to all involved personnel.´" In 2008, 114 fire fighters were killed in the line of duty.´^ These profound statistics place the health and safety of first responders at significant risk. Additionally, there is no established mechanism for identifying fatalities that result from illnesses such as forms of cancer that develop over long periods oftime, and which are often related to occupational exposure to hazardous materials or toxic products of combustion. The lAFF, therefore, requests continued renewal of funding under the NIEHS Hazardous Waste Workers Training Program (HWWTP) to further train first responders in hazardous materials, with a focus on health and safety. In the following paragraphs, the lAFF will document its past successes and effectiveness in planning, implementing and operating worker health and safety training programs and employing adult education techniques. Since receiving its first NIEHS award in 1987, the lAFF has updated its existing programs and developed new programs to meet the changing needs of the target population. To date, the lAFF has developed 15 training programs to meet the needs of first responders. Many of these classes are offered in an Instructor Training/Train-ttie-Trainer (TtT) format, allowing departments to develop their own, in-house cadre of instructors. The lAFF´s past successes in performance and effectiveness of training programs will be discussed in great detail throughout this proposal. lAFF training programs are designed to meet or exceed minimum requirements of federal regulations and national industry standards. These training programs incorporate information on potential hazards, describe appropriate actions including the use of personal protective and other rescue equipment, and stress the importance of preplanning. Additionally, lAFF training programs are designed to meet the needs of the adult learner, and incorporate students´ accumulated knowledge and experience. The lAFF provides seven key components of adult learning 1. An environment where students feel safe and supported, where individual needs and uniqueness are honored, where abilities and life achievements are acknowledged and respected. 2. An environment that fosters intellectual freedom and encourages experimentation and creativity. 3. An environment where instructors treat adult students as peers, accepted and respected as intelligent experienced adults, whose opinions are listened to, honored and appreciated. 4. Self-directed learning, where students take responsibility for their own learning. The lAFF designs individual learning programs that address what each person needs and wants to learn, in order to function optimally in their profession. 5. Pacing or intellectual challenge. Optimal pacing is challenging people just beyond their present level of ability. 6. Active involvement in learning, as opposed to passively listening to lectures. Where students and instructors interact and dialogue, where exercises and experiences are used to bolster facts and theory, adults grow more. 7. Regular feedback mechanisms for students to tell master instructors what works best for them and what they want and need to learn, and instructors who hear and make changes based on student input. Summarv of worker health and safetv activities for the last five years for the maior participating organizations in the proposed program
Keywords: Achievement; Address; Adult; Award; base; Communities; Consensus; Creativeness; design; Educational aspects; Educational Curriculum; Effectiveness; emergency service/first responder; Emergency Situation; Environment; Equipment; Exercise; experience; Exposure to; Feedback; Fire - disasters; Fostering; Freedom; Funding; hazard; Hazardous Substances; Hazardous Waste; Health; Hearing; Housing; Human Resources; Individual; Industry; Injury; instructor; International; Killings; Knowledge; Learning; lectures; Life; Malignant Neoplasms; meetings; Names; National Institute of Environmental Health Sciences; Occupational Exposure; peer; Performance; Persons; Programmed Learning; programs; Regulation; Reporting; response; Risk; Running; Safety; Services; statistics; Stress; Students; success; Target Populations; Techniques; theories; Training; Training Programs; Transportation; U-Series Cooperative Agreements; United States; Update; Work
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5U45ES006167-20_7157 (2011): $849228
HAZMAT DISASTER PREPAREDNESS TRAINING PROGRAM (HDPTP)
J Patrick
International Association Fire Fighterscity: Washington country: United States (us)
Abstract: Fire departments provide invaluable services to communities nationwide. They respond to all emergency situations. They also respond to mergency service calls and good intent calls. Often what is described to dispatchers does not reflect the actual incident. Nevertheless, fire departments are trained and prepared to respond to a broad array of situations. Each year in the United States approximately 100 fire fighters are killed while on duty. Although the number of fire fighter fatalities has steadily decreased over the past 20 years, the incidence of fire fighter fatalities per 100,000 incidents has actually risen. Despite a downward dip in the early 1990s, the level of fire fighter fatalities is back up to the same levels experienced in the 1980s.´ In 2005, 80,000 fire fighter injuries in the line-of-duty were reported¿an increase of 5.6 percent from the year before. In 2006, an estimated 83,000 fire fighter injuries were reported as occurring in the line-of-duty." Even with considerable amounts of training, many injuries can be prevented by making simple behavioral modifications and adopting safety as a primary value. For example, although national standards requiring seat belts have been in place since 1987, statistics from the United States Fire Administration (USFA) show fire fighter fatalities in motor vehicle crashes (MVC), where seat belts were not worn, persist. In cases where the use of seat belts was known, 3 of 4 fatalities were not wearing their seat belt.´" Research shows safety problems occur at the individual, group/team (crew), overall organization (fire department) and systems (fire service and emergency response agencies) levels. The lAFF supports the NIEHS WETP belief that pre-incident training is critical for workers who may find themselves responding to a disaster. The lAFF´s Frontline Safety curriculum seeks to address this. This program enhances the safety and health training of current hazardous materials workers and chemical responders (fire fighters) and augments prevention preparedness efforts in a wide variety of high-risk settings. The safety culture in the fire service is, in many cases, responsible for unfortunate, preventable accidents and fatalities. In order to reverse these preventable accidents/predictable surprises, it is important to understand both safety and culture. Fire fighters have come to accept the above unfortunate statistics as part of doing the "business" they are in. Those statistics are unacceptable. Fire fighters can reduce injuries and fatalities, if they act with safety as the primary value. The lAFF, therefore, requests continued renewal of funding under the NIEHS Hazardous Disaster Preparedness Training Program (HDPTP) to further train first responders in hazardous materials, with a focus on health and safety. In the following paragraphs, the lAFF will document its past successes and effectiveness in planning, implementing and operating worker health and safety training programs and employing adult education techniques. Since receiving its first NIEHS award in 1987, the lAFF has updated its existing programs and developed new programs to meet the changing needs of the target population. To date, the lAFF has developed 15 training programs to meet the needs of first responders. Many of these classes are offered in an Instructor Training/Train-the-Trainer (TtT) format, allowing departments to develop their own, in-house cadre of instructors. The lAFF´s past successes in performance and effectiveness of training programs will be discussed in great detail throughout this proposal. lAFF training programs are designed to meet or exceed minimum requirements of federal regulations and national industry standards. These training programs incorporate information on potential hazards, describe appropriate actions personal protective and other rescue equipment, and stress the importance of preplanning. Additionally, lAFF training programs are designed to meet the needs of the adult learner, and incorporate students´ accumulated knowledge and experience. The lAFFprovides seven key components of adult learning 1. An environment where students feel safe and supported, where individual needs and uniqueness are honored, where abilities and life achievements are acknowledged and respected. 2. An environment that fosters intellectual freedom and encourages experimentation and creativity. 3. An environment where instructors treat adult students as peers, accepted and respected as intelligent experienced adults, whose opinions are listened to, honored and appreciated. 4. Self-directed learning, where students take responsibility for their own learning. The lAFF designs individual learning programs that address what each person needs and wants to learn, in order to function optimally in their profession. 5. Pacing or intellectual challenge. Optimal pacing is challenging people just beyond their present level of ability. 6. Active involvement in learning, as opposed to passively listening to lectures. Where students and instructors interact and dialogue, where exercises and experiences are used to bolster facts and theory, adults grow more. 7. Regular feedback mechanisms for students to tell master instructors what works best for them and what they want and need to learn, and instructors who hear and make changes based on student input. Summary of worker health and safetv activities for the last five years for the major participating organizations in the proposed program
Keywords: Accidents; Achievement; Address; Adopted; Adult; Award; Back; base; Behavior Therapy; Belief; Businesses; Chemicals; Communities; Consensus; Creativeness; design; Disasters; Educational aspects; Educational Curriculum; Effectiveness; Emergency medical service; emergency service/first responder; Emergency Situation; Environment; Equipment; Exercise; experience; Feedback; Fire - disasters; Fostering; Freedom; Funding; hazard; Hazardous Substances; Health; health training; Hearing; high risk; Housing; Incidence; Individual; Industry; Injury; instructor; International; Killings; Knowledge; Learning; lectures; Life; meetings; National Institute of Environmental Health Sciences; peer; Performance; Persons; prevent; Prevention; Programmed Learning; programs; Readiness; Regulation; Reporting; Research; response; Safety; Seat Belts; Services; statistics; Stress; Students; success; System; Target Populations; Techniques; theories; Trainers Training; Training; Training Programs; U-Series Cooperative Agreements; United States; Update; Vehicle crash; Work
Budget start date: 4-AUG-2011
Budget end date: 31-JUL-2012
5U45ES006167-20_7158 (2011): $327777
PERSONALIZED PHYSICIAN LEARNING INTERVENTION TO IMPROVE HYPERTENSION CONTROL
J Patrick, Senior Clinical Investigator
Healthpartners Research Foundationcity: Minneapolis country: United States (us)
Grant 5R01HL089451-04 from National Heart, Lung, And Blood Institute
Abstract: Each year 46 million Americans with uncontrolled hypertension (HT) make well over 150 million office visits to about 150,000 primary care physicians (PCPs). Each of these visits represents an opportunity to intensify HT therapy, but over 80% of the time, no change in therapy is made. These data suggest that an effective HT improvement intervention must reduce therapeutic inertia in primary care, and be simple and inexpensive enough to facilitate broad dissemination. Personalized Physician Learning (PPL) is a powerful strategy to change behavior that has yet to be applied to HT care provided by PCPs. In this project we assess the impact of two PPL interventions that differ in how they identify patterns of physician decision making in HT care. The first intervention, REAL-PPL, uses real EMR-derived data to direct the personalized learning intervention. The second intervention, SIM-PPL, uses physician performance on simulated cases to direct the personalized learning intervention. Both interventions are delivered via the web to PCPs who complete a minimum of 12 simulated HT learning cases that address therapeutic inertia and each physician´s specific identified failures of decision making in HT care. The learning cases used in both interventions embody principles of adaptive learning, and provide three kinds of learning feedback (of actual BP values, graphic data displays, and specific clinical management suggestions) an average of 15 times per learning case. To test the hypothesis that these interventions improve HT control, we group randomize 39 clinics with their 120 PCPs and 6,000 adult patients with uncontrolled HT to one of three study arms (a) REAL+PPL Intervention, (b) SIM+PPL Intervention, or (c) No Intervention (control group). Hierarchical logistic models (MLwiN) that accommodate nested data are used to compare each intervention to control group, and to evaluate differences between the REAL+PPL and SIM+PPL interventions. Secondary analysis quantifies the impact of interventions on therapeutic inertia and on a defined set of specific failures of physician decision making in HT care. Formal cost-effectiveness analysis provides key information to guide dissemination of interventions, if successful. Dissemination is supported by (a) the low cost and easy transportability of SIM+PPL, (b) the appeal of REAL+PPL to medical groups with EMRs, (c) the prevalence, clinical complications, and costs of uncontrolled HT, and (d) participation of PCP and managed care leaders in the project. Results have the potential to improve the care of millions of Americans who silently suffer the ravages of one of the most devastating and hard to control chronic diseases of all time.A major obstacle to better hypertension care in the United States is failure of physicians to intensify therapy in a timely and effective way. This project takes advantage of electronic medical record technology to (a) assess physician patterns of hypertension care, (b) based on each physician´s observed patterns of care, develop and deliver via the Web a sophisticated physician-specific set of learning interventions, and (c) assess the impact of these learning interventions on quality of care delivered to real patients with hypertension. Results have the potential to improve the care of millions of Americans who silently suffer the ravages of one of the most devastating and hard to control chronic diseases of all time
Keywords: Address; Adult; American; base; Behavior; behavior change; Blood Pressure; Caring; Chronic Disease; Chronic Kidney Failure; Clinic; Clinical; Clinical Management; Cognitive Science; Computerized Medical Record; Congestive Heart Failure; Control Groups; cost; cost effectiveness; Cost Effectiveness Analysis; Data; Data Display; Decision Making; design; End stage renal failure; Environment; Failure (biologic function); Feedback; group intervention; Health; Healthcare; Hypertension; hypertension control; improved; Individual; Internet; Intervention; Learning; Logistic Models; Managed Care; Medical; Methods; Myocardial Infarction; Office Visits; Patients; Pattern; Patterns of Care; Performance; Physicians; post intervention; Prevalence; Primary Care Physician; Primary Health Care; Psychological Transfer; Quality of Care; Randomized; Relative (related person); Research; response; Series; Simulate; stroke; successful intervention; Suggestion; Technology; Testing; theories; Therapeutic; therapy design; three-arm study; Time; United States; Visit; Work
Project start date: 2008-06-01
Project end date: 2012-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01HL089451-04 (2011): $296317
IMPROVING DEPRESSION TREATMENT OUTCOMES WITH AN INSULIN-SENSITIZING AGENT
J Patrick, Professor Of Psychiatry
Washington Universitycity: Saint Louis country: United States (us)
Grant 5R01MH081150-05 from National Institute Of Mental Health
Abstract: Depression affects 1 in 4 individuals with type 2 diabetes, the principal manifestation of insulin resistance (IR), and is associated with hyperglycemia, diabetes complications, and mortality. Glycemic control improves significantly with depression treatment, and the gains are sustained throughout the subsequent depression- free interval. However, current depression treatment strategies fail to induce recovery in one-half of these patients and permit recurrence in one-third within a year. Several lines of evidence indicate that IR (depression-related or depression-independent) interferes with response to depression treatment and maintenance of the depression-free state. Therefore, we propose a two-phase (acute, 16 weeks; maintenance, 24 weeks), randomized, double-blind, placebo-controlled trial of treatment for major depressive disorder (MDD) in persons with IR, testing the following hypothesis reduction in depression symptoms is greater (acute phase) and recurrence of depression is delayed (maintenance phase) in patients receiving insulin sensitizer augmentation of conventional antidepressant pharmacotherapy compared to patients treated with conventional pharmacotherapy alone. 200 subjects with MDD and IR [BMI >28.7 kg/m2 and homeostasis model of insulin resistance (HOMA-IR) >3.6] receive sertraline (SRT) and additional randomly assigned treatment with rosiglitazone (ROS) or placebo (PBO). For practical and ethical reasons, only patients with IR and without overt diabetes will be included. Those meeting criteria for MOD recovery will continue treatment for an additional 6 months while nonrecovered subjects will be referred for out-of- study depression management. Measures of depression, IR (from OGTT minimal model), glycemia, anthropometries, treatment adherence, physical activity and quality of life will be taken at baseline (pre- treatment) and the point of depression recovery/nonrecovery. In the recovered subset, additional measures will be taken at the time of MDD recurrence or 6 months after recovery in those remaining depression free. The primary endpoints are the reduction in depression symptom severity during the acute phase and elapsed time-to-recurrence (TTR) of MDD during the maintenance phase. Multiple regression (acute phase) and Cox proportional hazards models (maintenance phase) will be used to determine treatment effects as well as independent predictors of depression improvement and TTR. The principal hypotheses are that reduction in depression is greater and TTR is significantly longer in patients treated with SRT+ROS compared to those receiving SRT+PBO, and that reduction in IR independently predicts these favorable outcomes. If the hypotheses are supported, the study would have far-reaching scientific and public health implications It will identify a novel treatment and a new treatment target for enhancing responsiveness to antidepressant therapy and lengthening the subsequent depression-free interval in patients with IR (With or without diabetes). The findings would represent a significant advance in depression treatment
Keywords: Abate; Acute; Affect; Amputation; Anthropometry; Antidepressive Agents; Blindness; Body Composition; Cardiovascular Diseases; Cause of Death; Clinical; Clinical Treatment; Complications of Diabetes Mellitus; Cox Proportional Hazards Models; Depressed mood; depressive symptoms; Diabetes Mellitus; diet and exercise; double-blind placebo controlled trial; End stage renal failure; Epidemic; Ethics; Exposure to; glycemic control; Goals; Healthcare; heuristics; Homeostasis; Hydrocortisone; Hyperglycemia; improved; Individual; Insulin; Insulin Resistance; insulin sensitivity; insulin sensitizing drugs; Lifetime Risk; Limb structure; Maintenance; Major Depressive Disorder; Measures; meetings; Mental Depression; Metformin; Modeling; Mortality Vital Statistics; Non-Insulin-Dependent Diabetes Mellitus; novel; OGTT; Outcome; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physical activity; Placebos; Population; Prevalence; Prevention; public health medicine (field); Quality of life; Randomized; Randomized Clinical Trials; Recovery; Recurrence; Research; response; Risk; rosiglitazone; Sampling; Sertraline; Severities; Testing; Time; treatment adherence; treatment effect; Treatment outcome; treatment strategy
Project start date: 2007-09-10
Project end date: 2012-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
5R01MH081150-05 (2011): $627772
INVADER LNAS AS NOVEL GENE SPECIFIC THERAPEUTICS
J Patrick
University Of Idahocity: Moscow country: United States (us)
Grant 5R01GM088697-03 from National Institute Of General Medical Sciences
Abstract: Compounds that sequence-specifically bind target regions in chromosomal DNA in living cells hold tremendous potential as therapeutics, general research tools and diagnostic probes. DNA-targeting probes can modulate expression of genes involved in diseases, facilitate correction of detrimental mutations by targeted delivery of DNA-modifying agents or allow direct fluorescent labeling of chromosomal DNA. Progress in this area has been achieved with triplex forming oligonucleotides, minor groove binding polyamides, and peptide nucleic acids, but major methodological limitations have impeded development of drug candidates. Accordingly, there remains an extensive need for a DNA-targeting strategy which exhibits a) fast, high affinity binding, b) gene- specific targeting (> 15 bp) of chromosomal DNA without sequence restrictions at physiologically relevant ionic strengths, c) excellent biostability, d) uncomplicated DNA-like handling and e) straightforward design. We propose Invader Locked Nucleic Acids (LNAs) as a solution to this grand challenge. This strategy is based on our discovery that a) oligonucleotides modified with intercalator-functionalized 2´-amino-¿-L-LNA monomers exhibit unsurpassed affinity toward DNA targets, b) duplex probes with ´monomer zippers´ are exceedingly unstable, which c) generates a thermodynamic driving force for duplex probes to dissociate and bind double stranded DNA targets. The objective of this proposal is to maximize the DNA-targeting affinity of Invader LNA and to test the hypothesis that optimized Invader LNA can target chromosomal DNA and modulate gene expression in living cells. Specifically, we propose to a) optimize DNA-targeting of Invader LNA by chemical structural engineering of the monomer zippers (energetic hotspots) and the probe architecture, and b) demonstrate binding and modulation of gene expression by optimized Invader LNA in specific gene promoter regions using cultured cell models - these gene promoter regions will be studied in co-transfected plasmids and in the context of endogenous chromosomal DNA. The proposed experiments will clearly establish the feasibility of Invader LNAs as a paradigm changing DNA-targeting strategy. The successful development of Invader LNA as a reliable, biostable and easily handled probe technology will allow a) strong, sequence- unrestricted and site-specific binding to accessible target regions of dsDNA under physiological conditions, b) modulation of gene expression, and/or c) targeted delivery of functional entities (DNA-modifying agents, donor DNA, chain cutters, optical labels or drugs) and will result in a marked acceleration in the development of drug candidates and tools for site-specific manipulation of DNA and have far-reaching implications in medicine, biology, and biotechnology. The availability of oligonucleotide-based probes, which a) allow reliable and site-specific binding under physiological conditions to accessible target regions of any sequence in plasmid or chromosomal DNA and b) facilitate efficient modulation of gene expression, will herald a new era in the treatment of gene-based pathologies. Every disease or malady that is the result of mutation or dis-regulated gene expression may be treatable by carefully designed and targeted invader LNAs
Keywords: Acceleration; Affinity; Architecture; Area; base; Binding (Molecular Function); Biology; Biotechnology; Cell model; Cells; Chemicals; Cultured Cells; design; Development; Diagnostic; Disease; DNA; driving force; drug candidate; ds-DNA; Engineering; Exhibits; Gene Expression; Genes; Health; Intercalating Agents; Ionic Strengths; Label; Life; locked nucleic acid; Medicine; Minor Groove; monomer; Mutation; novel; Nylons; Oligonucleotides; Optics; Pathology; Peptide Nucleic Acids; Pharmaceutical Preparations; Physiological; Plasmids; Promoter Regions (Genetics); Research; research study; Site; Solutions; targeted delivery; Technology; Testing; Therapeutic; Thermodynamics; tool
Relevance: Project Relevance The availability of oligonucleotide-based probes, which a) allow reliable and site-specific binding under physiological conditions to accessible target regions of any sequence in plasmid or chromosomal DNA and b) facilitate efficient modulation of gene expression, will herald a new era in the treatment of gene-based pathologies. Every disease or malady that is the result of mutation or dis-regulated gene expression may be treatable by carefully designed and targeted invader LNAs
Project start date: 2009-08-01
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: RFA-GM-09-008
5R01GM088697-03 (2011): $171914
J Patrick, Associate Professor
Cornell University Ithacacity: Ithaca country: United States (us)
Grant 5T32DK007158-36 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Completion of the Institute of Medicine´s reviews of nutrient based dietary standards and publication of the 2005 Dietary Guidelines for Americans and Healthy People 2010underscore the high and growing importance of nutritional Sciences to improving the public´s health. It is clear from these documents that the role of nutrition in promoting health and preventing chronic non-communicable diseases is second only to smoking prevention. The proposed program´s objective is to meet the multidisciplinary demands inherent to the research questions of greatest relevance to nutritional Sciences. Its specific aim is to train over a 5 year period approximately 20 research leaders for academia, government and the private for-profit and non-profit sectors in the area of nutritional Sciences. A broad range of disciplines is necessary to address this objective and specific aim. These are represented among the proposed training staff, i.e., genetics, molecular biology and biochemistry through sociology, psychology and economics. Externally funded research to complement a strong didactic program is available. NIH funding has grown from a value of$2.1 million in 2000-01, to a value of $10 million in 2003-04. Presently, the Division has 18funded or pending NIH awards worth a total value of $18.5 million. External research support from other federal, state, international, and private sources substantially augment this base. Resources for the continuing annual support of 11 trainees are sought. In the last four years the infrastructure for supporting the proposed training program has been strengthened significantly by the acquisition of equipment key to the program´s growing emphases in the nutritional genomics and tracer technologies, and more importantly by the recruitment and tenuring of key professionals with expertise in the biological and social sciences. The DNS´ research and training capabilities have been strengthened in areas such as population genetics, computational and developmental biology, epigenetic regulation, dietary/gene/cancer interrelationships, micronutrient regulation of the immune system, domestic nutrition interventions targeting low income groups, and the economics of "globalization´s" impact on diets throughout the world. These new strengths and the program´s documented contributions to the training of nutrition professionals presently in key positions in academia, government, and the for-profit and non-profit sectors support the training program´s objectives and specific aims
Keywords: 0-11 years old; 21+ years old; AAAS; Abnormal Assessment of Metabolism; Absorption; absorption; Academia; Achievement; Achievement Attainment; Address; adiposity; Admission; Admission activity; Adolescent; Adolescent Youth; Adult; adult human (21+); Advisory Committees; Age; Aging; agricultural; Agriculture; Alleles; allelic variant; Allelomorphs; American; American Association for the Advancement of Science; American Dietetic Association; Anemia; Animal Model; Animal Models and Related Studies; Appointment; Area; Articulation; Asia; Award; balance; balance function; base; Basic Research; Basic Science; Behavioral Sciences; Bio-Informatics; Biochemistry; Bioinformatics; Biologic Sciences; Biological; Biological Sciences; biological signal transduction; Biology; Birth; Birth Defects; Blood Coagulation Factor IV; Blood Pressure, High; body system, allergic/immunologic; body weight gain; body weight increase; bone; Bone; Bone and Bones; bone health; Bones and Bone Tissue; Book Chapters; Books; Ca++ element; Calcium; calcium metabolism; Cancer Genes; Cancer-Promoting Gene; Carbohydrates; Cardiovascular Diseases; cardiovascular disorder; Care, Health; career; Cell Communication and Signaling; Cell Signaling; Central Africa; Chair; Chairman; Chairperson; Chairwoman; Characteristics; Chemicals; Chemistry, Biological; Child; Child Youth; children; Children (0-21); Choice Behavior; Chronic; Chronic Disease; chronic disease/disorder; chronic disorder; Chronic Illness; Clinical Research; Clinical Study; Coagulation Factor IV; Collaborations; Colombia; Committee Members; Communication; Communities; Complement; Complement Proteins; Complex; Complex Genetic Trait; Computational Biology; Congenital Abnormality; Congenital Anatomic Abnormality; Congenital Anatomical Abnormality; Congenital Defects; Congenital Deformity; Congenital Malformation; corpulence; corpulency; corpulentia; Country; Critiques; Curriculum; Cystic Fibrosis; degenerative condition; degenerative disease; Degenerative Disorder; Dentistry; design; designing; Development; Development, Economic; Development, Economical; Developmental Biology; diabetes; Diabetes Mellitus; Diet; diet education; Diet Modification; Diet Surveys; Dietary Intervention; dietary survery; Dietetics; Dimensions; disability; Discipline; Disease; disease/disorder; Disorder; DNA Damage; DNA Injury; DNA Methylation; DNA Molecular Biology; Doctor of Philosophy; Eastern Europe; Economic Development; Economics; Editorial; editorial; Editorial (PT); Editorial [Publication Type]; Educational Curriculum; Educational process of instructing; Effectiveness; Embryo Development; Embryogenesis; Embryonic Development; Energy Expenditure; Energy Metabolism; enroll; Enrollment; Environment; environment effect on gene; Environmental Factor; environmental risk; Environmental Risk Factor; Epidemiology; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; epigenetic variation; Equilibrium; Equipment; Ethics; Ethnic group; Evolution; experience; experiment; experimental research; experimental study; EXTMR; Extramural; Extramural Activities; Factor IV; Faculty; Family; farmer; Fe element; fetal; Fetus; field study; flexibility; Food; Food Interactions; Food Policy; fortification; Foundations; Funding; Future; gene environment interaction; Gene Expression; gene product; Gene Transfer Techniques; Gene variant; Generalized Growth; Genes; Genetic; Genetic Algorithm; Genetic Diversity; Genetic Programming; Genetic Screening; Genetic Variation; Genome; Genomics; Genotype; Gestation; Government; Graduate Education; graduate student; Grant; Growth; Guidelines; H and E; Health; health care service utilization; Health Care Utilization; health services utilization; Healthcare; healthcare service utilization; healthcare utilization; heavy metal lead; heavy metal Pb; Hematoxylin and Eosin; Hematoxylin and Eosin Staining Method; Hereditary hemochromatosis; HIV Infections; Homologous Recombinational Repair; HOSP; Hospitals; Hour; HTLV-III Infections; HTLV-III-LAV Infections; Human; Human Genetics; Human Genome; Human, Adult; Human, Child; Human, General; hyperpiesia; hyperpiesis; Hypertension; hypertensive disease; Immune system; improved; Individual; Infant; Infrastructure; Institute of Medicine; Institute of Medicine (U.S.); Institutes; Institution; instrumentation; Instrumentation, Other; Interactions, Food; interdisciplinary approach; Interdisciplinary Research; Interdisciplinary Study; interest; Intermediary Metabolism; International; international center; Internships; Intervention Trial; Intracellular Communication and Signaling; Investments; Iron; iron metabolism; Joints; Journal Article; journal article; Journal Article (PT); Journal Article [Publication Type]; Journals; juvenile; juvenile human; Knowledge; Laboratories; Language; Latin America; Lead; Leadership; Life Sciences; Life Style; Lifestyle; Link; Location; Low income; Magazine; Maintenance; Maintenances; Mammals, Mice; Man (Taxonomy); Man, Modern; Maps; Marketing; Mass Spectrum; Mass Spectrum Analysis; Maternal Nutrition; maternal nutrition during pregnancy; Measures; Mediation; Medical center; medical schools; meetings; member; Mentors; Metabolic; metabolic abnormality assessment; Metabolic Processes; Metabolic Studies; Metabolism; Metabolism Studies; METBL; methyl group; Methylation; Mice; Micronutrients; Middle East; Minerals; Minor; Minority; Mission; model organism; Modeling; Modifications, Dietary; Molecular; Molecular Biology; Molecular Genetic Abnormality; Monitor; mother nutrition; Mothers; Mucoviscidosis; multidisciplinary; Multidisciplinary Collaboration; Multidisciplinary Research; Murine; Mus; NAS/IOM; National Institutes of Health; National Institutes of Health (U.S.); Negotiating; Negotiation; Neonatal; Netherlands; new growth; New York; NIH; novel; Nutrient; nutrient interaction; nutrient requirement; Nutrition; nutrition; nutrition education; Nutrition Interventions; Nutrition Policy; Nutrition Research; Nutritional; Nutritional Interventions; Nutritional Requirements; Nutritional Science; Nutritional Study; obese; obese people; obese person; obese population; Obesity; Oklahoma; Oncogenes; ontogeny; Oral; organ system, allergic/immunologic; Outcome; Paper; Participant; Parturition; Patients; Pb element; Personal Satisfaction; Ph.D.; PhD; Philosophy; Phlebotomy; Photometry/Spectrum Analysis, Mass; physical science; Physicians; Physiologic; Physiological; Plant Embryos; Play; Policies; Policy Research; Population; Population Genetics; Position; Positioning Attribute; post-doc; post-doctoral; Postdoc; Postdoctoral Fellow; pre-doc; pre-doctoral; predoc; predoctoral; preference; Pregnancy; Pregnancy in Adolescence; Pregnancy in Minors; Pregnancy, Adolescent; pregnant; prevent; preventing; Prize; Process of absorption; professor; programs; Programs (PT); Programs [Publication Type]; Protein Methylation; Proteins; Proteomics; prototype; Psychology; psychosocial; Public Health; public health medicine (field); Public Policy; Publications; Publishing; Qualifying; Recombination Repair; recombinational repair; Recommendation; Records; recruit; Recruitment Activity; Regulation; Research; Research Associate; Research Design; research facility; Research Infrastructure; Research Institute; Research Resources; research study; Research Support; Research Training; residence; Resources; Risk; Role; Running; Sampling; school age; School-Age Population; Schools; Science; Science of genetics; Science of nutrition; Scientific Publication; screening; Screening procedure; screenings; seed; Seeds; Senescence; senescent; Series; Services; Signal Transduction; Signal Transduction Systems; Signaling; simulation; Site; skills; Smoking Prevention; social; social role; Social Sciences; Sociology; Source; Space Flight; Spaceflight; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; stable isotope; Staging; Structure; Students; study design; Study Type; Study, Interdisciplinary; Survey Instrument; Surveys; T-Lymphotropic Virus Type III Infections, Human; Tag; Task Forces; Teaching; Technology; Teen Pregnancy; Teenage Pregnancy; Testing; Thinking; Thinking, function; Tissue Growth; tool; Tracer; Training; Training Programs; trait; Transforming Genes; Transgenesis; treatment utilization; Underage Pregnancy; United Nations; United States National Institutes of Health; Universities; Variation (Genetics); Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Venous blood sampling; VIT D; Vitamin D; Vitamins; Weight Gain; Weight Increase; well-being; Woman; Work; Writing; wt gain; youngster; Youth; Youth 10-21; Zinc; Zn element; Zygotes, Plant
Project start date: 1976-07-01
Project end date: 2011-12-31
Budget start date: 1-JAN-2011
Budget end date: 31-DEC-2011
PFA/PA: PA-02-109
5T32DK007158-36 (2011): $326285
CHILDHOOD HYPERTENSION AND OBESITY: DIAGNOSIS, CARE, AND COSTS
J Patrick, Senior Clinical Investigator
Healthpartners Research Foundationcity: Minneapolis country: United States (us)
Grant 5R01HL093345-03 from National Heart, Lung, And Blood Institute
Abstract: Child & Adolescent Hypertension Diagnosis, Care, and Costs. The rising prevalence of elevated BP in children and adolescents is a clinical and public health problem of increasing importance. Adolescents with sustained elevated blood pressure (BP) develop increased left ventricular mass, altered vascular reactivity and increased cIMT within a short period of time. Moreover, they often progress to subsequent hypertension as adults, which substantially increase risk of multiple serious clinical sequels´ later in life. Although an estimated 7% of children and adolescents have elevated BP, we have only a very limited understanding of the stability over time of BP classification categories recently established by the Fourth Report on High Blood Pressure in Children and Adolescents in 2004, and little is known about patterns of care provided to children and adolescents with elevated BP, or the resource use implications of elevated BP in these age groups. This project will address these critical gaps in knowledge using detailed clinical data extracted through Electronic Medical Records (EMR) at large medical groups in Colorado, Minnesota, and California. Available data for all study subjects includes all diastolic and systolic BP measures, weight, height, age, gender, race/ethnicity, comorbid conditions, medications, and laboratory test results over a 6-year study period. These EMR data are derived from an estimated study population of 80,000 children and adolescents age 0-17 years at baseline with at least one elevated BP. These data will be used to address the following specific aims (i) Assess in detail the stability over time of the recently developed categories of Pre-Hypertension (Pre-HT) and hypertension (HT) in children and adolescents, (ii) assess patterns of care provided to children with elevated BP (including serial BP measurement, diagnosis, work-up, lifestyle interventions, and pharmacologic management), and (iii) assess the impact of elevated BP on health care resource use in children and adolescents. By addressing these specific aims, results will (a) provide information to validate or modify recent Task Force recommendations, (b) document strengths and deficits in care currently provided to children and adolescents with elevated BP to guide the design of future care improvement initiatives, (c) quantify for health plan managers and payers the cost of elevated BP in children, (d) develop sophisticated capability for electronic surveillance of patterns of care provided to those with specific chronic diseases in the EMR era, and (e) identify a large, well-defined, and self-refreshing population of potential study subjects for future intervention trials to improve care for children and adolescents with elevated BP or associated conditions. This study, examining the status of health care for children with high blood pressure, will provide information to validate or modify current practice recommendations, document strengths and deficits in care currently provided to children and adolescents, and demonstrate to health plan managers and payers the cost of elevated BP in children. The results will be of great benefit to public health by providing a deeper understanding of the relationship between childhood hypertension and obesity and its´ impact on health in adulthood
Keywords: 17 year old; 18 year old; Address; Adolescence; Adolescent; Adult; Advisory Committees; Affect; Age; age group; Awareness; base; Blood Pressure; Blood Vessels; Body mass index; California; Caring; Categories; Characteristics; Child; Child Care; Child health care; Childhood; Chronic Disease; Classification; Clinic; Clinical; Clinical Data; Clinical Trials; Code; Cohort Studies; Colorado; Communities; community based practice; Computerized Medical Record; Congestive Heart Failure; coronary artery calcification; cost; Data; Databases; demographics; design; Diagnosis; diagnosis evaluation; Diagnostic; Dyslipidemias; Economics; Electronics; Enrollment; epidemiologic data; Epidemiologic Studies; Epidemiology; Ethnicity aspects; Event; experience; Expert Opinion; Future; Gender; Guidelines; Health; Health Planning; Healthcare; Height; Hypertension; improved; innovation; Insulin Resistance; Intervention; Intervention Trial; intima media; Kidney Failure; Knowledge; Laboratories; Lead; Left Ventricular Hypertrophy; Left Ventricular Mass; Life; lifestyle intervention; Measurement; Measures; Medical; Medication Management; Minnesota; Modification; Myocardial Infarction; Natural History; normotensive; Obesity; Overweight; Patients; Patterns of Care; Pharmaceutical Preparations; Pharmacy facility; Physicians; Population; Population Study; Prevalence; Procedures; Provider; public health medicine (field); public health relevance; Publications; Publishing; Race; Recommendation; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Risk; Risk Factors; sex; Site; Staging; stroke; Structure; Study Subject; surveillance data; System; Test Result; Testing; Thick; Time; Update; Validation; Variant; Weight; Weights and Measures
Relevance: This study, examining the status of health care for children with high blood pressure, will provide information to validate or modify current practice recommendations, document strengths and deficits in care currently provided to children and adolescents, and demonstrate to health plan managers and payers the cost of elevated BP in children. The results will be of great benefit to public health by providing a deeper understanding of the relationship between childhood hypertension and obesity and its´ impact on health in adulthood
Project start date: 2009-08-15
Project end date: 2013-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01HL093345-03 (2011): $726176
IDENTIFYING PATHOGENIC PROTEIN AGGREGATES IN ALS THROUGH AUTOCATALYTIC MISFOLDING
J Patrick
Denver Health And Hospital Authoritycity: Denver country: United States (us)
Grant 5R21NS054754-02 from National Institute Of Neurological Disorders And Stroke
Abstract: Amyotrophic lateral sclerosis (ALS) is an incurable disease marked by a relentless dying-off of motor neurons that causes paralysis then death. Ninety percent of cases occur sporadically and the cause of these cases is not known. Strong evidence indicates that abnormal aggregation of some cell protein or proteins causes sporadic ALS, but these proteins have not been conclusively identified, nor has the cause of the aggregation been determined. The hypothesis behind our proposal is that protein aggregation in ALS is driven by a self-propagating, or "autocatalytic" process of protein aggregation that is analogous to the process of aggregation that causes prion diseases, but involves a protein different from the prion protein. We aim to exploit recently developed methods, known as protein misfolding cyclic amplification (PMCA), that efficiently propagate aggregated prion protein in vitro to identify this putative protein that aggregates to cause ALS. In outline, the procedure we propose is as follows A small amount ("seed") of homogenized spinal cord tissue from persons who died of sporadic ALS will be mixed with a larger amount of normal spinal cord tissue. Simultaneously, a homogenate of normal cord seeded with normal cord will be prepared. The two homogenate mixes will be subjected to a modified PMCA procedure. Putative autocatalytically aggregating proteins from the ALS spinal cord will cause the same protein to specifically aggregate in the normal cord. We will compare the aggregated proteins in the two samples. Those proteins that aggregate only when "seeded" by ALS cord are likely to be autocatalytic aggregates and potentially the cause of sporadic ALS. PMCA procedures were not designed for the proteome-wide studies we proposed, so we will systematically modify the procedures to minimize non-autocatalytic aggregation while maintaining autocatalytic aggregation, using the prion protein as a surrogate for the putative ALS-causing protein. We will also use PMCA to look for autocatalytic aggregation of TDP-43, a protein recently identified to aggregate in spinal cord neurons of persons with sporadic ALS. These studies have the potential to determine the cause of sporadic ALS, a disease that kills almost 6000 Americans annually, and for which there is no effective treatment. A specific target protein and a pathogenic process for curative therapies may be identified. Further, if successful, the approach can be readily modified to use as an tool for high-throughput screening of potentially therapeutic compounds
Keywords: 2 Dimensional Gel Electrophoresis; aberrant protein folding; abnormal protein folding; ALS; American; Amyotrophic Lateral Sclerosis; Animals; base; Body Tissues; Brain; brain tissue; brain volume; Cell Fractionation; Cells; Central Nervous System; Cessation of life; Clinical; computational modeling; computational models; computational simulation; computer based models; Computer Simulation; computerized modeling; Computerized Models; computerized simulation; Condition; copper zinc superoxide dismutase; CuZnSOD; d-Numb; Data; Death; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; design; designing; Detergents; Disease; disease-associated PrP; disease/disorder; Disorder; Electrophoresis, Gel, 2-D; Electrophoresis, Gel, 2D; Electrophoresis, Gel, Two-Dimensional; Encephalon; Encephalons; Familial Amyotrophic Lateral Sclerosis; Gehrig`s Disease; gene product; Goals; heavy metal lead; heavy metal Pb; High Throughput Assay; high throughput screening; improved; in silico; In Vitro; in vitro Assay; in vivo; Infectious Agent; infectious organism; insoluble aggregate; interest; Investigation; Killings; Kinetic; Kinetics; Lead; Lou Gehrig Disease; Mammals, Mice; Mass Spectrum; Mass Spectrum Analysis; Mathematical Model Simulation; Mathematical Models and Simulations; Medulla Spinalis; Methods; Methods and Techniques; Methods, Other; Mice; Modeling; Models, Computer; motoneuron; Motor Cell; Motor Neuron Disease, Amyotrophic Lateral Sclerosis; Motor Neurons; Murine; Mus; Nerve Cells; Nerve Unit; Nervous System, Brain; Nervous System, CNS; Neural Cell; Neuraxis; Neurocyte; Neurodegenerative Diseases; Neurodegenerative Disorders; neurodegenerative illness; Neurologic; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Neurological; neuronal; Neurons; numb protein; Palsy; Paralysed; paralysis; paralytic; pathologic protein folding; Patients; Pb element; Persons; Photometry/Spectrum Analysis, Mass; Plant Embryos; Plegia; Prion Disease Pathway; Prion Diseases; Prion Protein Diseases; Prion Proteins; Prion-Induced Disorder; Prions; Procedures; Process; Production; protein aggregate; protein aggregation; protein mis-folding; protein misfolding; protein misfolding cyclic amplification; protein structure; protein TDP-43; Proteins; Proteome; Proteomics; PrP 33-35; PrP Proteins; PrP Sc; PrP(Sc); PrP-res; PrPSc; PrPSc Proteins; Rate; RNA-Binding Proteins; Sampling; Scrapie PrP; Scrapie PrP 33-35; seed; Seeds; Simulation, Computer based; Solutions; Sonication; Sp 33-35; Specificity; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; Spinal Cord; spongiform degeneration; Spongiform Encephalopathies, Transmissible; spongiform encephalopathy; Stabilizing Agents; subcellular fractionation; TDP-43; Techniques; Temperature; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; tool; Transgenic Model; Transmissible Dementias; virtual simulation; Zygotes, Plant
Project start date: 2007-07-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2008
Budget end date: 30-JUN-2011
PFA/PA: PA-06-181
5R21NS054754-02 (2008): $151080
E-PROSTANOID RECEPTOR SUBTYPE 2 (EP2) REGULATION OF MICROGLIAL ACTIVATION
J Patrick
University Of Washingtoncity: Seattle country: United States (us)
Grant 5F30AG030914-02 from National Institute On Aging
Abstract: Activation of innate immune response in microglia is associated with the initiation or progression of several neurodegenerative diseases. Perhaps best studied in models of Alzheimer´s disease (AD), innate immune activation has been shown to have both beneficial and deleterious effects on neurons. Beneficial effects are related to the clearance of nerurotoxic species of Abeta peptides, while paracrine damage to neurons results from the elaboration of a variety of toxic substances including reactive oxygen and nitrogen species. A major goal of many academic and pharmaceutical laboratories is to identify means to augment or maintain the beneficial actions of innate immune activation while suppressing paracrine neurotoxicity. Recently we demonstrated that genetic ablation of the EP2 receptor from primary mouse microglia resulted in the highly desirable dual phenotype of an increase in phagocytosis of Abeta species and complete blockade of paracrine neurotoxicity. Others have validated our findings using different methods. Taken together, these data strongly support EP2 receptor as a highly promising target for manipulating microglial innate immune response in AD and perhaps other neurodegenerative diseases. The mechanisms by which EP2-mediated signaling is related to Abeta phagocytosis and paracrine neurotoxicity are not known. Our Preliminary Data of mouse primary microglia expression identified a candidate gene that is tightly associated to EP2. We are aware of no report on the actions of this gene in any brain cells, including microglia. However, given emerging data we hypothesize that its expression and activity are mechanistically linked to EP2 signaling and that it may be a key element by which ablation of EP2 generated the highly desirable dual phenotype of enhanced Abeta phagocytosis and reduced paracrine neurotoxicity. We will test this hypothesis through the following Specific Aims 1) Perform in vitro validation of our candidate mRNA and protein expression in wild type and EP2-/- primary mouse microglia before and after Abeta treatment. 2) Map the in vivo regional and cellular brain distribution in wild type mice and a transgenic mouse model of AD before and after following bone-marrow transplantation from either wild type or EP2-/- mice. 3) Determine the functionality of its expression in the context of the EP2-/- dual phenotype in both knockout mice and a microglial cell line using shRNA knockdown
Keywords: Ablation; aged; Alzheimer`s Disease; Alzheimer`s disease model; Amyloid beta-Protein; base; Bone Marrow Transplantation; Brain; brain cell; Candidate Disease Gene; Cell Line; cell type; Cells; cytokine; Data; Deposition; Dinoprostone; Elements; Exhibits; Genes; Genetic; Goals; Hematopoietic; Hippocampus (Brain); HIV encephalitis; Human; immune activation; Immune response; In Vitro; in vivo; Inflammatory; Injection of therapeutic agent; Kinesis; Knockout Mice; Laboratories; Link; Lymphocyte; Maps; Mediating; member; Methods; Microglia; migration; mouse model; mRNA Expression; Mus; mutant; Neurodegenerative Disorders; Neurons; neurotoxic; neurotoxicity; Nitrogen; oxidative damage; Oxygen; paracrine; Parkinson Disease; Peptides; Phagocytosis; Pharmacologic Substance; Phenotype; Physiology; Poisons; Production; prostaglandin EP2 receptor; Prostaglandins; protein expression; Protein Family; receptor; Regulation; Reporting; response; Role; Signal Pathway; Signal Transduction; small hairpin RNA; Surveys; Testing; Transgenic Mice; Validation; Ventricular; Wild Type Mouse
Project start date: 2009-12-01
Project end date: 2012-11-30
Budget start date: 1-DEC-2010
Budget end date: 30-NOV-2011
PFA/PA: PA-05-151
5F30AG030914-02 (2011): $34106
INTERNALIZING PATHWAYS TO DRUG USE: A MULTI-SAMPLE ANALYSIS
J Patrick
University Of North Carolina Chapel Hillcity: Chapel Hill country: United States (us)
Grant 5R01DA015398-08 from National Institute On Drug Abuse
Keywords: 5 year old; Adolescence; Adolescent; Adult; Affect; Age; age difference; aged; Alcohol or Other Drugs use; Alcoholism; Alcohols; anti social; Anxiety; Archives; Behavioral; Child; Childhood; children of alcoholics; Cognitive; cohort; college; Comorbidity; contextual factors; Data; Data Set; Deceleration; Depressed mood; depressive symptoms; design; Development; Disease; Drug usage; effective intervention; effective therapy; emerging adult; Etiology; experience; Family; Gender; Goals; Health; Health behavior; high risk; high school; Interview; Life; Literature; Longitudinal Studies; Marihuana; Mediating; Mental Depression; Methods; Michigan; Modeling; novel; Nursery Schools; Outcome; Parents; Participant; Pathway interactions; Pattern; Pharmaceutical Preparations; Phenotype; Population; population based; Prevention; Prevention program; Prevention strategy; problem drinker; Process; Research Personnel; Risk; Risk Factors; Sampling; Sampling Studies; Self Medication; social; Statistical Methods; stressor; Subgroup; Substance Use Disorder; Surveys; Symptoms; Temperament; Testing; theories; Time; Tobacco; trait; treatment program; Wood material; young adult; Youth
Relevance: Our proposal tests an internalizing pathway to substance use disorder over the first four decades of life. Studies of such early emerging but persistent pathways are rare but critical to efforts to design and implement effective intervention and treatment programs for youth
Project start date: 2002-08-15
Project end date: 2012-11-30
Budget start date: 1-DEC-2011
Budget end date: 30-NOV-2012
5R01DA015398-08 (2012): $392284
Sponsored Links Excellgen http://Excellgen.com
ENHANCING INTESTINAL & BRAIN UPTAKE OF ANTI-AIDS DRUGS
J Patrick, Parke-davis Chair Professor
Rutgers The St Univ Of Nj New Brunswickcity: New Brunswick country: United States (us)
Grant 4R37AI051214-10 from National Institute Of Allergy And Infectious Diseases
Keywords: Acquired Immune Deficiency; Acquired Immune Deficiency Syndrome; Acquired Immune Deficiency Syndrome Virus; Acquired Immuno-Deficiency Syndrome; Acquired Immunodeficiency Syndrome; Acquired Immunodeficiency Syndrome Virus; Adverse effects; Affinity; AIDS; AIDS Drugs; AIDS Virus; Amprenavir; Anti-AIDS Agents; Anti-AIDS Drugs; Anti-HIV Agents; Anti-HIV Drugs; Anti-Human Immunodeficiency Virus Agents; antiAIDS agent; Antiproteases; Antiviral Agents; Antiviral Drugs; Antivirals; APV; Arts; base; Be element; Be++ element; Beryllium; Binding; Binding (Molecular Function); Biologic Products; Biological Agent; Biological Products; biopharmaceutical; biotherapeutic agent; Blood; blood drug; Blood Plasma; body system, hepatic; Body Tissues; bowel; Brain; C-C Chemokine Receptor Type 5 Gene; C-C CKR-5 Gene; Carbamic acid, (3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(- phenylmethyl)propyl)-, tetrahydro-3-furanyl ester, (3S-(3R*(1S*, 2R*)))-; CC-CKR-5 Gene; CCCKR5 Gene; CCR-5 Gene; CCR5; CCR5 gene; CD195 Antigen Gene; CD4 Antigen (P55); CD4 Antigens; CD4 Molecule; CD4 Protein; Cell surface; Cell Surface Receptors; Cells; Chemoattractant Receptor; Chemokine (C-C) Receptor 5 Gene; Chemotactic Peptide Receptor; CHEMR13 Gene; CKR-5 Gene; CKR5 Gene; Clinical; CMKBR5 Gene; Complement; Complement Proteins; Compliance behavior; compliance cooperation; CXC-R4; CXCR-4; CXCR4; CXCR4 gene; D-Mannose; D2S201E; design; designing; Development; Dose; Drug Combinations; Drug Delivery; Drug Delivery Systems; drug development; Drug Kinetics; Drug Targeting; Drug Targetings; drug/agent; Drugs; Effectiveness; Encephalon; Encephalons; Endocytosis; Endopeptidase Inhibitors; Enzyme Interaction; F-Chemotactic Peptide Receptor; FB22; Filtration; fMet-Leu-Phe receptor; FMLP Receptor; Follicular Dendritic Cells; Formyl Peptide Receptor 1; FPR1; Fractionation, Filtration; Goals; Grant; Half-Life; Half-Lifes; helper T lymphocyte marker; Hematologic Agents; Hematological Agents; HIV; HIV Infections; HIV Peptide T; HIV-1; HIV-1 Fusion Co-Receptor Gene; HIV-I; HIV1; HM89; HSY3RR; HTLV-III; HTLV-III Infections; HTLV-III-LAV Infections; Human immunodeficiency virus 1; Human Immunodeficiency Viruses; human T cell leukemia virus III; human T lymphotropic virus III; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Immunodeficiency Virus Type 1, Human; Immunologic Deficiency Syndrome, Acquired; improved; In Vitro; in vivo; Instruction; Intestinal; Intestines; Investigation; Kidney; L-Threonine, N-(N-(N2-(N-(N-(N-(N-D-alanyl-L-seryl)-L-threonyl)-L-threonyl)-L-threonyl)-L-asparaginyl)-L-tyrosyl)-; LAP3; LAV-HTLV-III; LCR1; LESTR; life course; Life Cycle; Life Cycle Stages; Ligand Binding; Ligands; Liver; Lung; lymph flow; lymph gland; Lymph node proper; lymph nodes; Lymphadenopathy-Associated Virus; Lymphatic Tissue; Lymphoid Tissue; macrophage; Mannopyranose; Mannopyranoside; Mannose; mannose receptor; Medication; Methods; Molecular Interaction; N-formyl Hexapeptide Receptor; N-Formylmethionyl Peptide Receptor; nano carrier; nano particle; nano scale Science; nano tech; nano technology; nanocarrier; nanoparticle; Nanoscale Science; nanotech; Nanotechnology; Nervous System, Brain; norvir; novel; NPY3R; NPYR; NPYRL; NPYY3R; OKT4 antigen; Organ; organ system, hepatic; Outcome; pathway; Pathway interactions; patient adherence; Patient Compliance; Patient Cooperation; Patients; Pattern; Penetration; Peptidase Inhibitors; Peptide Hydrolase Inhibitors; Peptide Peptidohydrolase Inhibitors; Peptide Phage Display Library; Peptide T; Peptides; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacodynamics; Pharmacokinetics; Plasma; Polymers; pre-clinical; preclinical; Principal Investigator; programs; Programs (PT); Programs [Publication Type]; Property; Property, LOINC Axis 2; Protease Antagonists; Protease Inhibitor; Proteinase Inhibitors; pulmonary; receptor; Receptor Protein; Receptors, CD4; Receptors, Formyl Peptide; Receptors, Surface CD4; renal; Research; Respiratory System, Lung; response; Reticuloendothelial System, Blood; Reticuloendothelial System, Lymph Node; Reticuloendothelial System, Serum, Plasma; Reticuloendothelial System, Spleen; Reticuloendothelial System, Thymus; Ritonavir; RTV; scaffold; scaffolding; screening; Screening procedure; screenings; Serum, Plasma; side effect; Site; site targeted delivery; Spleen; Staging; System; System, LOINC Axis 4; T-Cell Antigen T4/Leu3; T-Cell Surface Antigen T4/Leu-3; T-Cells; T-Lymphocyte; T-Lymphotropic Virus Type III Infections, Human; T4 molecule; targeted delivery; Technology; tetrahydro-3-furyl N-(3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl-2-hydroxypropyl)carbamate; Therapeutic; Therapeutic Agents; therapy adverse effect; therapy compliance; therapy cooperation; Thymus; thymus derived lymphocyte; Thymus Gland; Thymus Proper; Thymus-Dependent Lymphocytes; Tissues; Transferrin Receptor; treatment adverse effect; Treatment Compliance; Treatment Side Effects; uptake; Urinary System, Kidney; Viral; Virus-HIV
Project start date: 2001-12-01
Project end date: 2016-02-29
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
4R37AI051214-10 (2011): $503315