Science.gov

Sample records for comprehensive human risk

  1. A comprehensive genetic approach for improving prediction of skin cancer risk in humans.

    PubMed

    Vazquez, Ana I; de los Campos, Gustavo; Klimentidis, Yann C; Rosa, Guilherme J M; Gianola, Daniel; Yi, Nengjun; Allison, David B

    2012-12-01

    Prediction of genetic risk for disease is needed for preventive and personalized medicine. Genome-wide association studies have found unprecedented numbers of variants associated with complex human traits and diseases. However, these variants explain only a small proportion of genetic risk. Mounting evidence suggests that many traits, relevant to public health, are affected by large numbers of small-effect genes and that prediction of genetic risk to those traits and diseases could be improved by incorporating large numbers of markers into whole-genome prediction (WGP) models. We developed a WGP model incorporating thousands of markers for prediction of skin cancer risk in humans. We also considered other ways of incorporating genetic information into prediction models, such as family history or ancestry (using principal components, PCs, of informative markers). Prediction accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) estimated in a cross-validation. Incorporation of genetic information (i.e., familial relationships, PCs, or WGP) yielded a significant increase in prediction accuracy: from an AUC of 0.53 for a baseline model that accounted for nongenetic covariates to AUCs of 0.58 (pedigree), 0.62 (PCs), and 0.64 (WGP). In summary, prediction of skin cancer risk could be improved by considering genetic information and using a large number of single-nucleotide polymorphisms (SNPs) in a WGP model, which allows for the detection of patterns of genetic risk that are above and beyond those that can be captured using family history. We discuss avenues for improving prediction accuracy and speculate on the possible use of WGP to prospectively identify individuals at high risk.

  2. Comprehensibility maximization and humanly comprehensible representations

    NASA Astrophysics Data System (ADS)

    Kamimura, Ryotaro

    2012-04-01

    In this paper, we propose a new information-theoretic method to measure the comprehensibility of network configurations in competitive learning. Comprehensibility is supposed to be measured by information contained in components in competitive networks. Thus, the increase in information corresponds to the increase in comprehensibility of network configurations. One of the most important characteristics of the method is that parameters can be explicitly determined so as to produce a state where the different types of comprehensibility can be mutually increased. We applied the method to two problems, namely an artificial data set and the ionosphere data from the well-known machine learning database. In both problems, we showed that improved performance could be obtained in terms of all types of comprehensibility and quantization errors. For the topographic errors, we found that updating connection weights prevented them from increasing. Then, the optimal values of comprehensibility could be explicitly determined, and clearer class boundaries were generated.

  3. Chernobyl accident: A comprehensive risk assessment

    SciTech Connect

    Vargo, G.J.; Poyarkov, V.; Baryakhtar, V.; Kukhar, V.; Los, I.

    1999-01-01

    The authors, all of whom are Ukrainian and Russian scientists involved with Chernobyl nuclear power plant since the April 1986 accident, present a comprehensive review of the accident. In addition, they present a risk assessment of the remains of the destroyed reactor and its surrounding shelter, Chernobyl radioactive waste storage and disposal sites, and environmental contamination in the region. The authors explore such questions as the risks posed by a collapse of the shelter, radionuclide migration from storage and disposal facilities in the exclusion zone, and transfer from soil to vegetation and its potential regional impact. The answers to these questions provide a scientific basis for the development of countermeasures against the Chernobyl accident in particular and the mitigation of environmental radioactive contamination in general. They also provide an important basis for understanding the human health and ecological risks posed by the accident.

  4. Chernobyl accident: A comprehensive risk assessment

    SciTech Connect

    Vargo, G.J.; Poyarkov, V.; Baryakhtar, V.; Kukhar, V.; Los, I.

    1999-11-01

    The authors, all of whom are Ukrainian and Russian scientists involved with Chernobyl nuclear power plant since the April 1986 accident, present a comprehensive review of the accident. In addition, they present a risk assessment of the remains of the destroyed reactor and its surrounding shelter, Chernobyl radioactive waste storage and disposal sites, and environmental contamination in the region. The authors explore such questions as the risks posed by a collapse of the shelter, radionuclide migration from storage and disposal facilities in the exclusion zone, and transfer from soil to vegetation and its potential regional impact. The answers to these questions provide a scientific basis for the development of countermeasures against the Chernobyl accident in particular and the mitigation of environmental radioactive contamination in general. They also provide an important basis for understanding the human health and ecological risks posed by the accident.

  5. The Chornobyl accident: A comprehensive risk assessment

    SciTech Connect

    Vargo, G.J.; Poyarkov, V.; Bar`yakhtar, V.; Kukhar, V.; Los, I.; Kholosha, V.; Shestopalov, V.

    1999-10-01

    The authors, all of whom are Ukrainian and Russian scientists involved with Chornobyl nuclear power plant since the April 1986 accident, present a comprehensive review of the accident. In addition, they present a risk assessment of the remains of the destroyed reactor and its surrounding shelter, Chornobyl radioactive waste storage and disposal sites, and environmental contamination in the region. The authors explore such questions as the risks posed by a collapse of the shelter, radionuclide migration from storage and disposal facilities in the exclusion zone, and transfer from soil to vegetation and its potential regional impact. The answers to these questions provide a scientific basis for the development of countermeasures against the Chornobyl accident in particular and the mitigation of environmental radioactive contamination in general. They also provide an important basis for understanding the human health and ecological risks posed by the accident.

  6. 12 CFR 324.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and correlations; (iv) Basis risk; (v) Recovery rate volatility as it relates to the propensity for recovery rates to affect tranche prices; and (vi) To the extent the comprehensive risk measure incorporates... sufficiently liquid to permit rebalancing during periods of stress; and (D) Capture in the comprehensive...

  7. Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma.

    PubMed

    del Pino, Marta; Bleeker, Maaike C G; Quint, Wim G; Snijders, Peter J F; Meijer, Chris J L M; Steenbergen, Renske D M

    2012-10-01

    The role of human papillomavirus (HPV) infections in the development of verrucous carcinoma, a well-differentiated variant of squamous cell carcinoma with difficult differential diagnosis, is controversial in the literature. In this study, we analysed verrucous carcinoma from different origins for the presence and activity of a broad spectrum of HPV types, and carefully reviewed the histopathological features. A random series of 27 formalin-fixed, paraffin-embedded specimens of verrucous carcinoma was taken, representing the head and neck region (n=6), anogenital area (n=16) and extragenital skin region (n=5). After review of the histological slides, all samples were subjected to different polymerase chain reaction-based HPV detection techniques, together detecting a total of 83 HPV types, including both mucosal and cutaneous types. Histological revision was carefully performed. Lesions with keratinised papillae, blunt stromal invaginations and minimal cytological atypia were considered verrucous carcinoma. Condylomatous lesions with viral changes were defined as giant condyloma. Verrucous lesions that did not meet those criteria were classified as verrucous hyperplasia. Tumours with stromal infiltration were considered as invasive squamous cell carcinoma. Histological revision revealed that 13 out of 27 cases were verrucous carcinoma (one showing a double infection with HPV 35 and 45), 5 invasive squamous cell carcinomas, 5 verrucous hyperplasia (one with a double infection with HPV 4 and 8), 1 pseudoepitheliomatous hyperplasia and 3 giant condylomas. All three giant condylomas were low-risk HPV positive (HPV 6 and 11) and showed active mRNA transcription. None of the HPV-positive samples tested positive for diffuse p16(INK4A) staining. In conclusion, our results do not support a causal role of HPV in the development of verrucous carcinoma. Testing for LR-HPV, particularly HPV 6 and 11, may help in the differential diagnosis of lesions suspicious of verrucous

  8. Comprehensive Review of Human Sapoviruses

    PubMed Central

    Katayama, Kazuhiko; Saif, Linda J.

    2015-01-01

    SUMMARY Sapoviruses cause acute gastroenteritis in humans and animals. They belong to the genus Sapovirus within the family Caliciviridae. They infect and cause disease in humans of all ages, in both sporadic cases and outbreaks. The clinical symptoms of sapovirus gastroenteritis are indistinguishable from those caused by noroviruses, so laboratory diagnosis is essential to identify the pathogen. Sapoviruses are highly diverse genetically and antigenically. Currently, reverse transcription-PCR (RT-PCR) assays are widely used for sapovirus detection from clinical specimens due to their high sensitivity and broad reactivity as well as the lack of sensitive assays for antigen detection or cell culture systems for the detection of infectious viruses. Sapoviruses were first discovered in 1976 by electron microscopy in diarrheic samples of humans. To date, sapoviruses have also been detected from several animals: pigs, mink, dogs, sea lions, and bats. In this review, we focus on genomic and antigenic features, molecular typing/classification, detection methods, and clinical and epidemiological profiles of human sapoviruses. PMID:25567221

  9. Human Research Risk Management

    NASA Image and Video Library

    Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and per...

  10. The effectiveness of group-based comprehensive risk-reduction and abstinence education interventions to prevent or reduce the risk of adolescent pregnancy, human immunodeficiency virus, and sexually transmitted infections: two systematic reviews for the Guide to Community Preventive Services.

    PubMed

    Chin, Helen B; Sipe, Theresa Ann; Elder, Randy; Mercer, Shawna L; Chattopadhyay, Sajal K; Jacob, Verughese; Wethington, Holly R; Kirby, Doug; Elliston, Donna B; Griffith, Matt; Chuke, Stella O; Briss, Susan C; Ericksen, Irene; Galbraith, Jennifer S; Herbst, Jeffrey H; Johnson, Robert L; Kraft, Joan M; Noar, Seth M; Romero, Lisa M; Santelli, John

    2012-03-01

    Adolescent pregnancy, HIV, and other sexually transmitted infections (STIs) are major public health problems in the U.S. Implementing group-based interventions that address the sexual behavior of adolescents may reduce the incidence of pregnancy, HIV, and other STIs in this group. Methods for conducting systematic reviews from the Guide to Community Preventive Services were used to synthesize scientific evidence on the effectiveness of two strategies for group-based behavioral interventions for adolescents: (1) comprehensive risk reduction and (2) abstinence education on preventing pregnancy, HIV, and other STIs. Effectiveness of these interventions was determined by reductions in sexual risk behaviors, pregnancy, HIV, and other STIs and increases in protective sexual behaviors. The literature search identified 6579 citations for comprehensive risk reduction and abstinence education. Of these, 66 studies of comprehensive risk reduction and 23 studies of abstinence education assessed the effects of group-based interventions that address the sexual behavior of adolescents, and were included in the respective reviews. Meta-analyses were conducted for each strategy on the seven key outcomes identified by the coordination team-current sexual activity; frequency of sexual activity; number of sex partners; frequency of unprotected sexual activity; use of protection (condoms and/or hormonal contraception); pregnancy; and STIs. The results of these meta-analyses for comprehensive risk reduction showed favorable effects for all of the outcomes reviewed. For abstinence education, the meta-analysis showed a small number of studies, with inconsistent findings across studies that varied by study design and follow-up time, leading to considerable uncertainty around effect estimates. Based on these findings, group-based comprehensive risk reduction was found to be an effective strategy to reduce adolescent pregnancy, HIV, and STIs. No conclusions could be drawn on the

  11. Comprehensive and comparative ecotoxicological and human risk assessment of polycyclic aromatic hydrocarbons (PAHs) in reef surface sediments and coastal seawaters of Iranian Coral Islands, Persian Gulf.

    PubMed

    Ranjbar Jafarabadi, Ali; Riyahi Bakhtiari, Alireza; Shadmehri Toosi, Amirhossein

    2017-11-01

    The concentration and spatial distribution along with ecotoxicological risk of 30 polycyclic aromatic hydrocarbons were investigated in the reef surface sediments (RSSs) and coastal seawater (CSW) of ten coral Islands from the Persian Gulf, Iran, in January 2015. For all sampling sites, assessment of ecological risk was undertaken using several approaches. Mean concentration of ∑30PAHs varied between 70 and 884ngL(-l) with an overall mean value of 464ngL(-l) in the CSW, while the RSS ranged from 274 to 1098ngg(-1)dw with a total average of 619ngg(-1)dw. The results showed a gradient in PAH concentration and toxicity estimates from the northern Hormoz site increasing to the eastern Kharg site. Most of the toxicity estimates were in the moderate range or less than risk values for damage to the marine environment. The calculated Dermal Hazard Quotient (HQs), the sum of HQs (HI) and other cancer risk values of most compounds were less than safety values at most sites. It means that the possibility of negative effects of PAHs via dermal absorption from sediments for children and adults is low. Some sampling sites studied have already been impacted with hazardous pollutants for an extended period of time and evidence from this investigation demonstrates that mixtures of PAHs may be carcinogenic to humans, especially in the western part of the Gulf. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. School-Linked Human Services: A Comprehensive Strategy for Aiding Students at Risk of School Failure. Report to the Chairman, Committee on Labor and Human Resources, U.S. Senate.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC. Div. of Human Resources.

    Since 1980, at least 8 states and more than 200 localities have developed programs that deliver a variety of health, social, and education services at or near schools. Many of the students served by these programs are at risk of failing in school or dropping out. These comprehensive school-linked programs are attempting to improve the educational…

  13. Comprehensive data analysis of human ureter proteome

    PubMed Central

    Magdeldin, Sameh; Hirao, Yoshitoshi; El Guoshy, Amr; Xu, Bo; Zhang, Ying; Fujinaka, Hidehiko; Yamamoto, Keiko; Yates, John R.; Yamamoto, Tadashi

    2016-01-01

    Comprehensive human ureter proteome dataset was generated from OFFGel fractionated ureter samples. Our result showed that among 2217 non-redundant ureter proteins, 751 protein candidates (33.8%) were detected in urine as urinary protein/polypeptide or exosomal protein. On the other hand, comparing ureter protein hits (48) that are not shown in corresponding databases to urinary bladder and prostate human protein atlas databases pinpointed 21 proteins that might be unique to ureter tissue. In conclusion, this finding offers future perspectives for possible identification of ureter disease-associated biomarkers such as ureter carcinoma. In addition, Cytoscape GO annotation was examined on the final ureter dataset to better understand proteins molecular function, biological processes, and cellular component. The ureter proteomic dataset published in this article will provide a valuable resource for researchers working in the field of urology and urine biomarker discovery. PMID:26937461

  14. NASA Human System Risk Assessment Process

    NASA Technical Reports Server (NTRS)

    Francisco, D.; Romero, E.

    2016-01-01

    NASA utilizes an evidence based system to perform risk assessments for the human system for spaceflight missions. The center of this process is the multi-disciplinary Human System Risk Board (HSRB). The HSRB is chartered from the Chief Health and Medical Officer (OCHMO) at NASA Headquarters. The HSRB reviews all human system risks via an established comprehensive risk and configuration management plan based on a project management approach. The HSRB facilitates the integration of human research (terrestrial and spaceflight), medical operations, occupational surveillance, systems engineering and many other disciplines in a comprehensive review of human system risks. The HSRB considers all factors that influence human risk. These factors include pre-mission considerations such as screening criteria, training, age, sex, and physiological condition. In mission factors such as available countermeasures, mission duration and location and post mission factors such as time to return to baseline (reconditioning), post mission health screening, and available treatments. All of the factors influence the total risk assessment for each human risk. The HSRB performed a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30, where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research and, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit for 6 and 12 months, deep space for 30 days and 1 year, a lunar mission for 1 year, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary

  15. Bihemispheric foundations for human speech comprehension.

    PubMed

    Bozic, Mirjana; Tyler, Lorraine K; Ives, David T; Randall, Billi; Marslen-Wilson, William D

    2010-10-05

    Emerging evidence from neuroimaging and neuropsychology suggests that human speech comprehension engages two types of neurocognitive processes: a distributed bilateral system underpinning general perceptual and cognitive processing, viewed as neurobiologically primary, and a more specialized left hemisphere system supporting key grammatical language functions, likely to be specific to humans. To test these hypotheses directly we covaried increases in the nonlinguistic complexity of spoken words [presence or absence of an embedded stem, e.g., claim (clay)] with variations in their linguistic complexity (presence of inflectional affixes, e.g., play+ed). Nonlinguistic complexity, generated by the on-line competition between the full word and its onset-embedded stem, was found to activate both right and left fronto-temporal brain regions, including bilateral BA45 and -47. Linguistic complexity activated left-lateralized inferior frontal areas only, primarily in BA45. This contrast reflects a differentiation between the functional roles of a bilateral system, which supports the basic mapping from sound to lexical meaning, and a language-specific left-lateralized system that supports core decompositional and combinatorial processes invoked by linguistically complex inputs. These differences can be related to the neurobiological foundations of human language and underline the importance of bihemispheric systems in supporting the dynamic processing and interpretation of spoken inputs.

  16. 12 CFR 217.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... equal to the total specific risk add-on for such positions as calculated under section 210 of this... according to the requirements in paragraph (b) of this section; or (B) The total specific risk add-on that... make available to the Board the results of the supervisory stress testing, including comparisons...

  17. The Chornobyl Accident: A Comprehensive Risk Assessment

    SciTech Connect

    Poyarkov, Victor A.; Vargo, George J.; George J. Vargo

    2000-01-01

    This book provides a comprehensive of the April 1986 Chornobyl Nuclear Power Plant accident and its short and long-term effects in the fourteen years since the accident. Chapters include: cause and description of the accident; the Shelter constructed to contain the remains the destroyed reactor, radioactive wastes arising from the accident, environmental contamination, individual and collective radiation doses, societal aspects, economic impact and conclusions. Appendices on radiological units, the medical consequences of the accident, and a list of acronym and abbreviations are included.

  18. 12 CFR 3.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... correlations; (iv) Basis risk; (v) Recovery rate volatility as it relates to the propensity for recovery rates... the hedge is sufficiently liquid to permit rebalancing during periods of stress; and (D) Capture in... positions. (c) Requirements for stress testing. (1) A national bank or Federal savings association must...

  19. Human autoimmune diseases: a comprehensive update.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Gershwin, M Eric

    2015-10-01

    There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade.

  20. Risk management frameworks for human health and environmental risks.

    PubMed

    Jardine, Cindy; Hrudey, Steve; Shortreed, John; Craig, Lorraine; Krewski, Daniel; Furgal, Chris; McColl, Stephen

    2003-01-01

    A comprehensive analytical review of the risk assessment, risk management, and risk communication approaches currently being undertaken by key national, provincial/state, territorial, and international agencies was conducted. The information acquired for review was used to identify the differences, commonalities, strengths, and weaknesses among the various approaches, and to identify elements that should be included in an effective, current, and comprehensive approach applicable to environmental, human health and occupational health risks. More than 80 agencies, organizations, and advisory councils, encompassing more than 100 risk documents, were examined during the period from February 2000 until November 2002. An overview was made of the most important general frameworks for risk assessment, risk management, and risk communication for human health and ecological risk, and for occupational health risk. In addition, frameworks for specific applications were reviewed and summarized, including those for (1)contaminated sites; (2) northern contaminants; (3) priority substances; (4) standards development; (5) food safety; (6) medical devices; (7) prescription drug use; (8) emergency response; (9) transportation; (10) risk communication. Twelve frameworks were selected for more extensive review on the basis of representation of the areas of human health, ecological, and occupational health risk; relevance to Canadian risk management needs; representation of comprehensive and well-defined approaches; generalizability with their risk areas; representation of "state of the art" in Canada, the United States, and/or internationally; and extent of usage of potential usage within Canada. These 12 frameworks were: 1. Framework for Environmental Health Risk Management (US Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997). 2. Health Risk Determination: The Challenge of Health Protection (Health and Welfare Canada, 1990). 3. Health Canada Decision

  1. Human System Risk Management for Space Flight

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey

    2015-01-01

    This brief abstract reviews the development of the current day approach to human system risk management for space flight and the development of the critical components of this process over the past few years. The human system risk management process now provides a comprehensive assessment of each human system risk by design reference mission (DRM) and is evaluated not only for mission success but also for long-term health impacts for the astronauts. The discipline of bioastronautics is the study of the biological and medical effects of space flight on humans. In 1997, the Space Life Sciences Directorate (SLSD) initiated the Bioastronautics Roadmap (Roadmap) as the "Critical Path Roadmap", and in 1998 participation in the roadmap was expanded to include the National Space Biomedical Research Institute (NSBRI) and the external community. A total of 55 risks and 250 questions were identified and prioritized and in 2000, the Roadmap was base-lined and put under configuration control. The Roadmap took into account several major advisory committee reviews including the Institute of Medicine (IOM) "Safe Passage: Astronaut care for Exploration Missions", 2001. Subsequently, three collaborating organizations at NASA HQ (Chief Health and Medical Officer, Office of Space Flight and Office of Biological & Physical Research), published the Bioastronautics Strategy in 2003, that identified the human as a "critical subsystem of space flight" and noted that "tolerance limits and safe operating bands must be established" to enable human space flight. These offices also requested a review by the IOM of the Roadmap and that review was published in October 2005 as "A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA's Bioastronautics Roadmap", that noted several strengths and weaknesses of the Roadmap and made several recommendations. In parallel with the development of the Roadmap, the Office of the Chief Health and Medical Officer (OCHMO) began a process in

  2. A comprehensive risk analysis of coastal zones in China

    NASA Astrophysics Data System (ADS)

    Wang, Guanghui; Liu, Yijun; Wang, Hongbing; Wang, Xueying

    2014-03-01

    Although coastal zones occupy an important position in the world development, they face high risks and vulnerability to natural disasters because of their special locations and their high population density. In order to estimate their capability for crisis-response, various models have been established. However, those studies mainly focused on natural factors or conditions, which could not reflect the social vulnerability and regional disparities of coastal zones. Drawing lessons from the experiences of the United Nations Environment Programme (UNEP), this paper presents a comprehensive assessment strategy based on the mechanism of Risk Matrix Approach (RMA), which includes two aspects that are further composed of five second-class indicators. The first aspect, the probability phase, consists of indicators of economic conditions, social development, and living standards, while the second one, the severity phase, is comprised of geographic exposure and natural disasters. After weighing all of the above indicators by applying the Analytic Hierarchy Process (AHP) and Delphi Method, the paper uses the comprehensive assessment strategy to analyze the risk indices of 50 coastal cities in China. The analytical results are presented in ESRI ArcGis10.1, which generates six different risk maps covering the aspects of economy, society, life, environment, disasters, and an overall assessment of the five areas. Furthermore, the study also investigates the spatial pattern of these risk maps, with detailed discussion and analysis of different risks in coastal cities.

  3. Risks and Complications of Coronary Angiography: A Comprehensive Review

    PubMed Central

    Tavakol, Morteza; Ashraf, Salman; Brener, Sorin J.

    2012-01-01

    Coronary angiography and heart catheterization are invaluable tests for the detection and quantification of coronary artery disease, identification of valvular and other structural abnormalities, and measurement of hemodynamic parameters. The risks and complications associated with these procedures relate to the patient’s concomitant conditions and to the skill and judgment of the operator. In this review, we examine in detail the major complications associated with invasive cardiac procedures and provide the reader with a comprehensive bibliography for advanced reading. PMID:22980117

  4. THE NATIONAL EXPOSURE RESEARCH LABORATORY'S COMPREHENSIVE HUMAN ACTIVITY DATABASE

    EPA Science Inventory

    EPA's National Exposure Research Laboratory (NERL) has combined data from nine U.S. studies related to human activities into one comprehensive data system that can be accessed via the world-wide web. The data system is called CHAD-Consolidated Human Activity Database-and it is ...

  5. THE NATIONAL EXPOSURE RESEARCH LABORATORY'S COMPREHENSIVE HUMAN ACTIVITY DATABASE

    EPA Science Inventory

    EPA's National Exposure Research Laboratory (NERL) has combined data from nine U.S. studies related to human activities into one comprehensive data system that can be accessed via the world-wide web. The data system is called CHAD-Consolidated Human Activity Database-and it is ...

  6. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  7. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  8. Toward a comprehensive taxonomy of human motives

    PubMed Central

    Talevich, Jennifer R.; Walsh, David A.; Iyer, Ravi; Chopra, Gurveen

    2017-01-01

    A major success in personality has been the development of a consensual structure of traits. However, much less progress has been made on the structure of an equally important aspect of human psychology: motives. We present an empirically and theoretically structured hierarchical taxonomy of 161 motives gleaned from a literature review from McDougall to the present and based on the cluster analysis of similarity judgments among these 161 motives, a broader sampling of motives than previous work. At the broadest level were: Meaning, Communion, and Agency. These divided into nine clusters: Morality & Virtue, Religion & Spirituality, Self-Actualization, Avoidance, Social Relating, Family, Health, Mastery & Competence, and Financial & Occupational Success. Each divided into more concrete clusters to form 5 levels. We discuss contributions to research on motives, especially recent work on goal systems, and the aiding of communication and systematization of research. Finally, we compare the taxonomy to other motive organizations. PMID:28231252

  9. Acceptability of human risk.

    PubMed

    Kasperson, R E

    1983-10-01

    This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility.

  10. Acceptability of human risk.

    PubMed Central

    Kasperson, R E

    1983-01-01

    This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility. PMID:6418541

  11. Fuzzy comprehensive evaluation-based disaster risk assessment of desertification in Horqin Sand Land, China.

    PubMed

    Wang, Yongfang; Zhang, Jiquan; Guo, Enliang; Sun, Zhongyi

    2015-02-03

    Desertification is a typical disaster risk event in which human settlements and living environments are destroyed. Desertification Disaster Risk Assessment can control and prevent the occurrence and development of desertification disasters and reduce their adverse influence on human society. This study presents the methodology and procedure for risk assessment and zoning of desertification disasters in Horqin Sand Land. Based on natural disaster risk theory and the desertification disaster formation mechanism, the Desertification Disaster Risk Index (DDRI) combined hazard, exposure, vulnerability and restorability factors and was developed mainly by using multi-source data and the fuzzy comprehensive evaluation method. The results showed that high risk and middle risk areas account for 28% and 23% of the study area, respectively. They are distributed with an "S" type in the study area. Low risk and very low risk areas account for 21% and 10% of the study area, respectively. They are distributed in the west-central and southwestern parts. Very high risk areas account for 18% of the study area and are distributed in the northeastern parts. The results can be used to know the desertification disaster risk level. It has important theoretical and practical significance to prevention and control of desertification in Horqin Sand Land and even in Northern China.

  12. Fuzzy Comprehensive Evaluation-Based Disaster Risk Assessment of Desertification in Horqin Sand Land, China

    PubMed Central

    Wang, Yongfang; Zhang, Jiquan; Guo, Enliang; Sun, Zhongyi

    2015-01-01

    Desertification is a typical disaster risk event in which human settlements and living environments are destroyed. Desertification Disaster Risk Assessment can control and prevent the occurrence and development of desertification disasters and reduce their adverse influence on human society. This study presents the methodology and procedure for risk assessment and zoning of desertification disasters in Horqin Sand Land. Based on natural disaster risk theory and the desertification disaster formation mechanism, the Desertification Disaster Risk Index (DDRI) combined hazard, exposure, vulnerability and restorability factors and was developed mainly by using multi-source data and the fuzzy comprehensive evaluation method. The results showed that high risk and middle risk areas account for 28% and 23% of the study area, respectively. They are distributed with an “S” type in the study area. Low risk and very low risk areas account for 21% and 10% of the study area, respectively. They are distributed in the west-central and southwestern parts. Very high risk areas account for 18% of the study area and are distributed in the northeastern parts. The results can be used to know the desertification disaster risk level. It has important theoretical and practical significance to prevention and control of desertification in Horqin Sand Land and even in Northern China. PMID:25654772

  13. Comprehensive methodology for ecological risk assessment of contaminated soils

    SciTech Connect

    Kuperman, R.G.

    1994-12-31

    Development of a comprehensive methodology for ecological risk assessment and monitoring of contaminated soils is essential to assess the impacts of environmental contaminants on soil community and biologically-mediated processes in soil. The proposed four-step plan involves (1) a thorough survey of the soil community to establish biodiversity and a base-line community structure, (2) toxicity trials on indicator species and whole soil invertebrate communities, (3) laboratory and field tests on indicator processes and (4) the use of statistical and simulation models to ascertain changes in the soil ecosystems. This methodology was used in portions of the US Army`s Aberdeen Proving Ground, Maryland as part of an ecological risk assessment. Previous soil analyses showed extensive surface soil contamination with metals, nitrate and PCBs. Preliminary results from field surveys of soil invertebrate communities showed significant reductions in total abundance of animals, reductions in the abundance of several taxonomic and functional groups of soil invertebrates, and changes in the activity of epigeic arthropods in contaminated areas when compared with the local ``background`` area. Laboratory tests also demonstrated that microbial activity and success of egg hatching of ground beetle Harpalus pensylvanicus were reduced in contaminated soils. These results suggest that impacts to soil ecosystems should be explicitly considered in ecological risk assessment. The proposed comprehensive methodology appears to offer an efficient and potentially cost saving tool for remedial investigations of contaminated sites.

  14. Use of comprehensive NEPA documents to reduce program risk

    SciTech Connect

    Wolff, T.A.; Hansen, R.P.

    1994-04-01

    Sandia National Laboratories operates DOE`s Kauai Test Facility (KTF) on the western coast of the Hawaiian island of Kauai. In July 1992, DOE approved a comprehensive Environmental Assessment (EA) covering ongoing and future rocket launches of experimental payloads. The KTF EA fulfilled two basic objectives: Consideration of environmental values early in the planning and decision making process; and public disclosure. These objectives can also be considered to be benefits of preparing comprehensive NEPA documents. However, proponents of an action are not as dedicated to these twin NEPA objectives as they are motivated by NEPA`s ability to reduce program risks. Once the KTF environmental assessment was underway, it was apparent that reducing risks to the program, budget, and schedule was the main incentive for successful completion of the EA. The comprehensive or ``omnibus`` environmental assessment prepared for the KTF is a de facto ``detailed statement,`` and it is also a good example of a ``mitigated FONSI,`` i.e., mitigation measures are essential to render some potential impacts not significant. Because the KTF EA is a broad scope, umbrella-like, site-wide assessment, it ``bounds`` the impacts of continuing and proposed future actions. The successful completion of this document eliminated the need to review, document, and gain approval individually for numerous related actions. Also, because it supported a Finding of No Significant Impact (FONSI) after identifying appropriate mitigation, it also eliminated the need for an environmental impact statement (EIS). This paper discusses seven specific ways in which the KTF EA reduced program risks and supported budget and schedule objectives.

  15. Neural mechanisms of discourse comprehension: a human lesion study

    PubMed Central

    Colom, Roberto; Grafman, Jordan

    2014-01-01

    Discourse comprehension is a hallmark of human social behaviour and refers to the act of interpreting a written or spoken message by constructing mental representations that integrate incoming language with prior knowledge and experience. Here, we report a human lesion study (n = 145) that investigates the neural mechanisms underlying discourse comprehension (measured by the Discourse Comprehension Test) and systematically examine its relation to a broad range of psychological factors, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores obtained from these factors were submitted to voxel-based lesion-symptom mapping to elucidate their neural substrates. Stepwise regression analyses revealed that working memory and extraversion reliably predict individual differences in discourse comprehension: higher working memory scores and lower extraversion levels predict better discourse comprehension performance. Lesion mapping results indicated that these convergent variables depend on a shared network of frontal and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The observed findings motivate an integrative framework for understanding the neural foundations of discourse comprehension, suggesting that core elements of discourse processing emerge from a distributed network of brain regions that support specific competencies for executive and social function. PMID:24293267

  16. Neural mechanisms of discourse comprehension: a human lesion study.

    PubMed

    Barbey, Aron K; Colom, Roberto; Grafman, Jordan

    2014-01-01

    Discourse comprehension is a hallmark of human social behaviour and refers to the act of interpreting a written or spoken message by constructing mental representations that integrate incoming language with prior knowledge and experience. Here, we report a human lesion study (n = 145) that investigates the neural mechanisms underlying discourse comprehension (measured by the Discourse Comprehension Test) and systematically examine its relation to a broad range of psychological factors, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores obtained from these factors were submitted to voxel-based lesion-symptom mapping to elucidate their neural substrates. Stepwise regression analyses revealed that working memory and extraversion reliably predict individual differences in discourse comprehension: higher working memory scores and lower extraversion levels predict better discourse comprehension performance. Lesion mapping results indicated that these convergent variables depend on a shared network of frontal and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The observed findings motivate an integrative framework for understanding the neural foundations of discourse comprehension, suggesting that core elements of discourse processing emerge from a distributed network of brain regions that support specific competencies for executive and social function.

  17. Toxic substances and human risk: principles of data interpretation

    SciTech Connect

    Tardiff, R.G.; Rodricks, J.V.

    1988-01-01

    This book provides a comprehensive overview of the relationship between toxicology and risk assessment and identifying the principles that should be used to evaluate toxicological data for human risk assessment. The book opens by distinguishing between the practice of toxicology as a science (observational and data-gathering activities) and its practice as an art (predictive or risk-estimating activities). This dichotomous nature produces the two elemental problems with which users of toxicological data must grapple. First, how relevant are data provided by the science of toxicology to assessment of human health risks. Second, what methods of data interpretation should be used to formulate hypotheses or predictions regarding human health risk.

  18. Comprehension of Novel Communicative Signs by Apes and Human Children.

    ERIC Educational Resources Information Center

    Tomasello, Michael; Call, Josep; Gluckman, Andrea

    1997-01-01

    Compared comprehension of novel communicative signs to assist 2.5- and 3-year-old humans, chimpanzees, and orangutans find hidden objects during a hiding-finding game. Found that children at both ages performed above chance with all signs. No ape performed above chance for any signs not known before the experiment despite three times as many…

  19. Studying the Human Immunome: The Complexity of Comprehensive Leukocyte Immunophenotyping

    PubMed Central

    Biancotto, Angélique

    2014-01-01

    A comprehensive study of the cellular components of the immune system requires both deep and broad immunophenotyping of numerous cell populations in an efficient and practical manner. In this chapter, we describe the technical aspects of studying the human immunome using high-dimensional (15 color) fluorescence-based immunophenotyping. We focus on the technical aspects of polychromatic flow cytometry and the initial stages in developing a panel for comprehensive leukocyte immunophenotyping (CLIP). We also briefly discuss how this panel is being used and the challenges of encyclopedic analysis of these rich data sets. PMID:23975032

  20. Studying the human immunome: the complexity of comprehensive leukocyte immunophenotyping.

    PubMed

    Biancotto, Angélique; McCoy, J Philip

    2014-01-01

    A comprehensive study of the cellular components of the immune system requires both deep and broad immunophenotyping of numerous cell populations in an efficient and practical manner. In this chapter, we describe the technical aspects of studying the human immunome using high-dimensional (15 color) fluorescence-based immunophenotyping. We focus on the technical aspects of polychromatic flow cytometry and the initial stages in developing a panel for comprehensive leukocyte immunophenotyping (CLIP). We also briefly discuss how this panel is being used and the challenges of encyclopedic analysis of these rich data sets.

  1. Distinct Neurocognitive Strategies for Comprehensions of Human and Artificial Intelligence

    PubMed Central

    Ge, Jianqiao; Han, Shihui

    2008-01-01

    Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence. PMID:18665211

  2. Distinct neurocognitive strategies for comprehensions of human and artificial intelligence.

    PubMed

    Ge, Jianqiao; Han, Shihui

    2008-07-30

    Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence.

  3. Transmission risk of human trichinellosis.

    PubMed

    Takumi, Katsuhisa; Teunis, Peter; Fonville, Manoj; Vallee, Isabelle; Boireau, Pascal; Nöckler, Karsten; van der Giessen, Joke

    2009-02-23

    Trichinella is a food-borne parasitic zoonoses and human cases are still reported in Europe mainly due to the consumption of pig meat originating from small backyard farms. Infections originating from industrialized pig farming have not been reported for decades in Europe, due to control measures to prevent the transmission of Trichinella from wildlife by indoor housing and good management practices. Therefore, risk-based monitoring programs might replace individual carcass control in industrialized pig farming as described in EU legislation SANCO 2075/2005. Transmission of Trichinella species between wildlife and the risk that may pose to humans via consumption of contaminated pork meat has not been studied quantitatively. One pathway by which human trichinellosis can occur is the rat-pig-human route. To evaluate the transmission risk though this pathway the dose responses of rat, pig, and human were studied. Experimental T. spiralis infection was performed in rats with doses of as few as 10 parasites and the data set was analysed using a newly developed dose response model that describes larvae per gram (LPG). Experimental T. spiralis infection in pig was analysed in a similar way. Furthermore nine published outbreaks of human trichinellosis were analysed to determine the dose response in humans. The risk of human trichinellosis via the rat-pig-human transmission was simulated by the Monte Carlo method. A pair of female and male parasites representing the lowest infection pressure from the environment, led to the probability of human trichinellosis by consumption of 100g of raw pork meat equal to 5% via the studied rat-pig-human pathway. In the absence of rodent control near the farm, a low infection pressure from wildlife presents a relatively high risk of human trichinellosis via consumption of uncooked pork meat.

  4. Tailoring risk communication to improve comprehension: Do patient preferences help or hurt?

    PubMed

    Barnes, Andrew J; Hanoch, Yaniv; Miron-Shatz, Talya; Ozanne, Elissa M

    2016-09-01

    Risk communication tools can facilitate patients' understanding of risk information. In this novel study, we examine the hypothesis that risk communication methods tailored to individuals' preferences can increase risk comprehension. Preferences for breast cancer risk formats, and risk comprehension data were collected using an online survey from 361 women at high risk for breast cancer. Women's initial preferences were assessed by asking them which of the following risk formats would be the clearest: (a) percentage, (b) frequency, (c) bar graph, (d) pictogram, and (e) comparison to other women. Next, women were presented with 5 different formats for displaying cancer risks and asked to interpret the risk information presented. Finally, they were asked again which risk format they preferred. Initial preferences for risk formats were not associated with risk comprehension scores. However, women with lower risk comprehension scores were more likely to update their risk format preferences after they evaluated risks in different formats. Less numerate women were more likely to prefer graphical rather than numeric risk formats. Importantly, we found that women preferring graphical risk formats had lower risk comprehension in these formats compared to numeric formats. In contrast, women preferring numeric formats performed equally well across formats. Our findings suggest that tailoring risk communication to patient preferences may not improve understanding of medical risks, particularly for less numerate women, and point to the potential perils of tailoring risk communication formats to patient preferences. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Comprehensive functional annotation of 77 prostate cancer risk loci.

    PubMed

    Hazelett, Dennis J; Rhie, Suhn Kyong; Gaddis, Malaina; Yan, Chunli; Lakeland, Daniel L; Coetzee, Simon G; Henderson, Brian E; Noushmehr, Houtan; Cozen, Wendy; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F; Haiman, Christopher A; Lu, Wange; Farnham, Peggy J; Coetzee, Gerhard A

    2014-01-01

    Genome-wide association studies (GWAS) have revolutionized the field of cancer genetics, but the causal links between increased genetic risk and onset/progression of disease processes remain to be identified. Here we report the first step in such an endeavor for prostate cancer. We provide a comprehensive annotation of the 77 known risk loci, based upon highly correlated variants in biologically relevant chromatin annotations--we identified 727 such potentially functional SNPs. We also provide a detailed account of possible protein disruption, microRNA target sequence disruption and regulatory response element disruption of all correlated SNPs at r(2) ≥ 0.88%. 88% of the 727 SNPs fall within putative enhancers, and many alter critical residues in the response elements of transcription factors known to be involved in prostate biology. We define as risk enhancers those regions with enhancer chromatin biofeatures in prostate-derived cell lines with prostate-cancer correlated SNPs. To aid the identification of these enhancers, we performed genomewide ChIP-seq for H3K27-acetylation, a mark of actively engaged enhancers, as well as the transcription factor TCF7L2. We analyzed in depth three variants in risk enhancers, two of which show significantly altered androgen sensitivity in LNCaP cells. This includes rs4907792, that is in linkage disequilibrium (r(2) = 0.91) with an eQTL for NUDT11 (on the X chromosome) in prostate tissue, and rs10486567, the index SNP in intron 3 of the JAZF1 gene on chromosome 7. Rs4907792 is within a critical residue of a strong consensus androgen response element that is interrupted in the protective allele, resulting in a 56% decrease in its androgen sensitivity, whereas rs10486567 affects both NKX3-1 and FOXA-AR motifs where the risk allele results in a 39% increase in basal activity and a 28% fold-increase in androgen stimulated enhancer activity. Identification of such enhancer variants and their potential target genes represents a

  6. Human Pose Estimation from Monocular Images: A Comprehensive Survey

    PubMed Central

    Gong, Wenjuan; Zhang, Xuena; Gonzàlez, Jordi; Sobral, Andrews; Bouwmans, Thierry; Tu, Changhe; Zahzah, El-hadi

    2016-01-01

    Human pose estimation refers to the estimation of the location of body parts and how they are connected in an image. Human pose estimation from monocular images has wide applications (e.g., image indexing). Several surveys on human pose estimation can be found in the literature, but they focus on a certain category; for example, model-based approaches or human motion analysis, etc. As far as we know, an overall review of this problem domain has yet to be provided. Furthermore, recent advancements based on deep learning have brought novel algorithms for this problem. In this paper, a comprehensive survey of human pose estimation from monocular images is carried out including milestone works and recent advancements. Based on one standard pipeline for the solution of computer vision problems, this survey splits the problem into several modules: feature extraction and description, human body models, and modeling methods. Problem modeling methods are approached based on two means of categorization in this survey. One way to categorize includes top-down and bottom-up methods, and another way includes generative and discriminative methods. Considering the fact that one direct application of human pose estimation is to provide initialization for automatic video surveillance, there are additional sections for motion-related methods in all modules: motion features, motion models, and motion-based methods. Finally, the paper also collects 26 publicly available data sets for validation and provides error measurement methods that are frequently used. PMID:27898003

  7. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

    PubMed

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression.

  8. Comprehensive identification and analysis of human accelerated regulatory DNA

    PubMed Central

    Gittelman, Rachel M.; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S.; Hawkins, R. David; Akey, Joshua M.

    2015-01-01

    It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

  9. Comprehensive brain MRI segmentation in high risk preterm newborns.

    PubMed

    Yu, Xintian; Zhang, Yanjie; Lasky, Robert E; Datta, Sushmita; Parikh, Nehal A; Narayana, Ponnada A

    2010-11-08

    Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes.

  10. Comprehension of iconic gestures by chimpanzees and human children.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2016-02-01

    Iconic gestures-communicative acts using hand or body movements that resemble their referent-figure prominently in theories of language evolution and development. This study contrasted the abilities of chimpanzees (N=11) and 4-year-old human children (N=24) to comprehend novel iconic gestures. Participants learned to retrieve rewards from apparatuses in two distinct locations, each requiring a different action. In the test, a human adult informed the participant where to go by miming the action needed to obtain the reward. Children used the iconic gestures (more than arbitrary gestures) to locate the reward, whereas chimpanzees did not. Some children also used arbitrary gestures in the same way, but only after they had previously shown comprehension for iconic gestures. Over time, chimpanzees learned to associate iconic gestures with the appropriate location faster than arbitrary gestures, suggesting at least some recognition of the iconicity involved. These results demonstrate the importance of iconicity in referential communication.

  11. Ecosystem Risk Assessment Using the Comprehensive Assessment of Risk to Ecosystems (CARE) Tool

    NASA Astrophysics Data System (ADS)

    Battista, W.; Fujita, R.; Karr, K.

    2016-02-01

    Effective Ecosystem Based Management requires a localized understanding of the health and functioning of a given system as well as of the various factors that may threaten the ongoing ability of the system to support the provision of valued services. Several risk assessment models are available that can provide a scientific basis for understanding these factors and for guiding management action, but these models focus mainly on single species and evaluate only the impacts of fishing in detail. We have developed a new ecosystem risk assessment model - the Comprehensive Assessment of Risk to Ecosystems (CARE) - that allows analysts to consider the cumulative impact of multiple threats, interactions among multiple threats that may result in synergistic or antagonistic impacts, and the impacts of a suite of threats on whole-ecosystem productivity and functioning, as well as on specific ecosystem services. The CARE model was designed to be completed in as little as two hours, and uses local and expert knowledge where data are lacking. The CARE tool can be used to evaluate risks facing a single site; to compare multiple sites for the suitability or necessity of different management options; or to evaluate the effects of a proposed management action aimed at reducing one or more risks. This analysis can help users identify which threats are the most important at a given site, and therefore where limited management resources should be targeted. CARE can be applied to virtually any system, and can be modified as knowledge is gained or to better match different site characteristics. CARE builds on previous ecosystem risk assessment tools to provide a comprehensive assessment of fishing and non-fishing threats that can be used to inform environmental management decisions across a broad range of systems.

  12. Ecosystem Risk Assessment Using the Comprehensive Assessment of Risk to Ecosystems (CARE) Tool

    NASA Astrophysics Data System (ADS)

    Battista, W.; Fujita, R.; Karr, K.

    2016-12-01

    Effective Ecosystem Based Management requires a localized understanding of the health and functioning of a given system as well as of the various factors that may threaten the ongoing ability of the system to support the provision of valued services. Several risk assessment models are available that can provide a scientific basis for understanding these factors and for guiding management action, but these models focus mainly on single species and evaluate only the impacts of fishing in detail. We have developed a new ecosystem risk assessment model - the Comprehensive Assessment of Risk to Ecosystems (CARE) - that allows analysts to consider the cumulative impact of multiple threats, interactions among multiple threats that may result in synergistic or antagonistic impacts, and the impacts of a suite of threats on whole-ecosystem productivity and functioning, as well as on specific ecosystem services. The CARE model was designed to be completed in as little as two hours, and uses local and expert knowledge where data are lacking. The CARE tool can be used to evaluate risks facing a single site; to compare multiple sites for the suitability or necessity of different management options; or to evaluate the effects of a proposed management action aimed at reducing one or more risks. This analysis can help users identify which threats are the most important at a given site, and therefore where limited management resources should be targeted. CARE can be applied to virtually any system, and can be modified as knowledge is gained or to better match different site characteristics. CARE builds on previous ecosystem risk assessment tools to provide a comprehensive assessment of fishing and non-fishing threats that can be used to inform environmental management decisions across a broad range of systems.

  13. Comprehensibility.

    ERIC Educational Resources Information Center

    Pettersson, Rune

    This paper addresses the difficulty involved in creating easily understood information. The act of communicating is not complete until the message has been both received and understood by the audience. Messages must always be comprehensible, otherwise they will have no effect. The readability, legibility, and reading value of a graphic message is…

  14. Metabolism of flavonoids in human: a comprehensive review.

    PubMed

    Chen, Zhongjian; Zheng, Shirui; Li, Liping; Jiang, Huidi

    2014-01-01

    Flavonoids are naturally occurring polyphenols, which are widely taken in diets, supplements and herbal medicines. Epidemiological studies have shown a flavonoid-rich diet is associated with the decrease in incidence of a range of diseases. Pharmacological evidences also reveal flavonoids display anti-oxidant, anti-allergic, anti-cancer, anti-inflammatory, anti-microbial and anti-diarrheal activities. Therefore, it is critical to study the biotransformation and disposition of flavonoids in human. This review summarizes the major metabolism pathways of flavonoids in human. First, lactase-phlorizin hydrolase (LPH) and human intestinal microflora mediate the hydrolysis of flavonoid glycosides, which is recognized as the first and determinant step in the absorption of flavonoids. Second, phase II metabolic enzymes (UGTs, SULTs and COMT) dominate the metabolism of flavonoids in vivo. UGTs are the most major contributors, followed by SULTs and COMT. By contrast, phase I metabolism pathway mediated by CYPs only plays a minor role. Third, the coupling of transporters (such as BCRP and MRPs) and phase II enzymes (UGTs and SULTs) plays an important role in the disposition of flavonoids, especially in the enteroenteric and enterohepatic circulations. Thus, all the above factors should be taken into consideration when studying pharmacokinetics of flavonoids. Here we describe a comprehensive metabolism profile of flavonoids, which will enhance our understanding of the mechanisms underlying the disposition and pharmacological effects of flavonoids in vivo.

  15. A comprehensive model for the humoral coagulation network in humans.

    PubMed

    Wajima, T; Isbister, G K; Duffull, S B

    2009-09-01

    Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.

  16. Prediction of Potential Cancer-Risk Regions Based on Transcriptome Data: Towards a Comprehensive View

    PubMed Central

    Alisoltani, Arghavan; Fallahi, Hossein; Ebrahimi, Mahdi; Ebrahimi, Mansour; Ebrahimie, Esmaeil

    2014-01-01

    A novel integrative pipeline is presented for discovery of potential cancer-susceptibility regions (PCSRs) by calculating the number of altered genes at each chromosomal region, using expression microarray datasets of different human cancers (HCs). Our novel approach comprises primarily predicting PCSRs followed by identification of key genes in these regions to obtain potential regions harboring new cancer-associated variants. In addition to finding new cancer causal variants, another advantage in prediction of such risk regions is simultaneous study of different types of genomic variants in line with focusing on specific chromosomal regions. Using this pipeline we extracted numbers of regions with highly altered expression levels in cancer condition. Regulatory networks were also constructed for different types of cancers following the identification of altered mRNA and microRNAs. Interestingly, results showed that GAPDH, LIFR, ZEB2, mir-21, mir-30a, mir-141 and mir-200c, all located at PCSRs, are common altered factors in constructed networks. We found a number of clusters of altered mRNAs and miRNAs on predicted PCSRs (e.g.12p13.31) and their common regulators including KLF4 and SOX10. Large scale prediction of risk regions based on transcriptome data can open a window in comprehensive study of cancer risk factors and the other human diseases. PMID:24796549

  17. Comprehensive comparative homeobox gene annotation in human and mouse

    PubMed Central

    Wilming, Laurens G.; Boychenko, Veronika; Harrow, Jennifer L.

    2015-01-01

    Homeobox genes are a group of genes coding for transcription factors with a DNA-binding helix-turn-helix structure called a homeodomain and which play a crucial role in pattern formation during embryogenesis. Many homeobox genes are located in clusters and some of these, most notably the HOX genes, are known to have antisense or opposite strand long non-coding RNA (lncRNA) genes that play a regulatory role. Because automated annotation of both gene clusters and non-coding genes is fraught with difficulty (over-prediction, under-prediction, inaccurate transcript structures), we set out to manually annotate all homeobox genes in the mouse and human genomes. This includes all supported splice variants, pseudogenes and both antisense and flanking lncRNAs. One of the areas where manual annotation has a significant advantage is the annotation of duplicated gene clusters. After comprehensive annotation of all homeobox genes and their antisense genes in human and in mouse, we found some discrepancies with the current gene set in RefSeq regarding exact gene structures and coding versus pseudogene locus biotype. We also identified previously un-annotated pseudogenes in the DUX, Rhox and Obox gene clusters, which helped us re-evaluate and update the gene nomenclature in these regions. We found that human homeobox genes are enriched in antisense lncRNA loci, some of which are known to play a role in gene or gene cluster regulation, compared to their mouse orthologues. Of the annotated set of 241 human protein-coding homeobox genes, 98 have an antisense locus (41%) while of the 277 orthologous mouse genes, only 62 protein coding gene have an antisense locus (22%), based on publicly available transcriptional evidence. PMID:26412852

  18. Comprehensive comparative homeobox gene annotation in human and mouse.

    PubMed

    Wilming, Laurens G; Boychenko, Veronika; Harrow, Jennifer L

    2015-01-01

    Homeobox genes are a group of genes coding for transcription factors with a DNA-binding helix-turn-helix structure called a homeodomain and which play a crucial role in pattern formation during embryogenesis. Many homeobox genes are located in clusters and some of these, most notably the HOX genes, are known to have antisense or opposite strand long non-coding RNA (lncRNA) genes that play a regulatory role. Because automated annotation of both gene clusters and non-coding genes is fraught with difficulty (over-prediction, under-prediction, inaccurate transcript structures), we set out to manually annotate all homeobox genes in the mouse and human genomes. This includes all supported splice variants, pseudogenes and both antisense and flanking lncRNAs. One of the areas where manual annotation has a significant advantage is the annotation of duplicated gene clusters. After comprehensive annotation of all homeobox genes and their antisense genes in human and in mouse, we found some discrepancies with the current gene set in RefSeq regarding exact gene structures and coding versus pseudogene locus biotype. We also identified previously un-annotated pseudogenes in the DUX, Rhox and Obox gene clusters, which helped us re-evaluate and update the gene nomenclature in these regions. We found that human homeobox genes are enriched in antisense lncRNA loci, some of which are known to play a role in gene or gene cluster regulation, compared to their mouse orthologues. Of the annotated set of 241 human protein-coding homeobox genes, 98 have an antisense locus (41%) while of the 277 orthologous mouse genes, only 62 protein coding gene have an antisense locus (22%), based on publicly available transcriptional evidence.

  19. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. Copyright © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  20. An anatomically comprehensive atlas of the adult human brain transcriptome

    PubMed Central

    Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

    2014-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

  1. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  2. Human DNA ligases: a comprehensive new look for cancer therapy.

    PubMed

    Singh, Deependra Kumar; Krishna, Shagun; Chandra, Sharat; Shameem, Mohammad; Deshmukh, Amit Laxmikant; Banerjee, Dibyendu

    2014-05-01

    Living organisms belonging to all three domains of life, viz., eubacteria, archaeabacteria, and eukaryotes encode one or more DNA ligases. DNA ligases are indispensable in various DNA repair and replication processes and a deficiency or an inhibition of their activity can lead to accumulation of DNA damage and strand breaks. DNA damage, specially strand breaks at unsustainable levels can lead to replication block and/or cell death. DNA ligases as potential anticancer targets have been realized only recently. There is enough rationale to suggest that ligases have a tremendous potential for novel therapeutics including anticancer and antibacterial therapy, specially when the world is facing acute problems of drug resistance and chemotherapy failure, with an immediate need for new therapeutic targets. Here, we review the current state of the art in the development of human ligase inhibitors, their structures, molecular mechanisms, physiological effects, and their potential in future cancer therapy. Citing examples, we focus on strategies for improving the activity and specificity of existing and novel inhibitors by using structure-based rational approaches. In the end, we describe potential new sites on the ligase I protein that can be targeted for the development of novel inhibitors. This is the first comprehensive review to compile all known human ligase inhibitors and to provide a rationale for the further development of ligase inhibitors for cancer therapy. © 2013 Wiley Periodicals, Inc.

  3. Paths to Reading Comprehension in At-Risk Second-Grade Readers

    ERIC Educational Resources Information Center

    Berninger, Virginia W.; Abbott, Robert D.; Vermeulen, Karin; Fulton, Cynthia M.

    2006-01-01

    Two studies of second graders at risk for reading disability, which were guided by levels of language and functional reading system theory, focused on reading comprehension in this population. In Study 1 (n = 96), confirmatory factor analysis of five comprehension measures loaded on one factor in both fall and spring of second grade. Phonological…

  4. Paths to Reading Comprehension in At-Risk Second-Grade Readers

    ERIC Educational Resources Information Center

    Berninger, Virginia W.; Abbott, Robert D.; Vermeulen, Karin; Fulton, Cynthia M.

    2006-01-01

    Two studies of second graders at risk for reading disability, which were guided by levels of language and functional reading system theory, focused on reading comprehension in this population. In Study 1 (n = 96), confirmatory factor analysis of five comprehension measures loaded on one factor in both fall and spring of second grade. Phonological…

  5. A comprehensive Network Security Risk Model for process control networks.

    PubMed

    Henry, Matthew H; Haimes, Yacov Y

    2009-02-01

    The risk of cyber attacks on process control networks (PCN) is receiving significant attention due to the potentially catastrophic extent to which PCN failures can damage the infrastructures and commodity flows that they support. Risk management addresses the coupled problems of (1) reducing the likelihood that cyber attacks would succeed in disrupting PCN operation and (2) reducing the severity of consequences in the event of PCN failure or manipulation. The Network Security Risk Model (NSRM) developed in this article provides a means of evaluating the efficacy of candidate risk management policies by modeling the baseline risk and assessing expectations of risk after the implementation of candidate measures. Where existing risk models fall short of providing adequate insight into the efficacy of candidate risk management policies due to shortcomings in their structure or formulation, the NSRM provides model structure and an associated modeling methodology that captures the relevant dynamics of cyber attacks on PCN for risk analysis. This article develops the NSRM in detail in the context of an illustrative example.

  6. A comprehensive map of mobile element insertion polymorphisms in humans.

    PubMed

    Stewart, Chip; Kural, Deniz; Strömberg, Michael P; Walker, Jerilyn A; Konkel, Miriam K; Stütz, Adrian M; Urban, Alexander E; Grubert, Fabian; Lam, Hugo Y K; Lee, Wan-Ping; Busby, Michele; Indap, Amit R; Garrison, Erik; Huff, Chad; Xing, Jinchuan; Snyder, Michael P; Jorde, Lynn B; Batzer, Mark A; Korbel, Jan O; Marth, Gabor T

    2011-08-01

    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations.

  7. Comprehensive quantification of ceramide species in human stratum corneum.

    PubMed

    Masukawa, Yoshinori; Narita, Hirofumi; Sato, Hirayuki; Naoe, Ayano; Kondo, Naoki; Sugai, Yoshiya; Oba, Tsuyoshi; Homma, Rika; Ishikawa, Junko; Takagi, Yutaka; Kitahara, Takashi

    2009-08-01

    One of the key challenges in lipidomics is to quantify lipidomes of interest, as it is practically impossible to collect all authentic materials covering the targeted lipidomes. For diverse ceramides (CER) in human stratum corneum (SC) that play important physicochemical roles in the skin, we developed a novel method for quantification of the overall CER species by improving our previously reported profiling technique using normal-phase liquid chromatography-electrospray ionization-mass spectrometry (NPLC-ESI-MS). The use of simultaneous selected ion monitoring measurement of as many as 182 kinds of molecular-related ions enables the highly sensitive detection of the overall CER species, as they can be analyzed in only one SC-stripped tape as small as 5 mm x 10 mm. To comprehensively quantify CERs, including those not available as authentic species, we designed a procedure to estimate their levels using relative responses of representative authentic species covering the species targeted, considering the systematic error based on intra-/inter-day analyses. The CER levels obtained by this method were comparable to those determined by conventional thin-layer chromatography (TLC), which guarantees the validity of this method. This method opens lipidomics approaches for CERs in the SC.

  8. A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

    PubMed Central

    Walker, Jerilyn A.; Konkel, Miriam K.; Stütz, Adrian M.; Urban, Alexander E.; Grubert, Fabian; Lam, Hugo Y. K.; Lee, Wan-Ping; Busby, Michele; Indap, Amit R.; Garrison, Erik; Huff, Chad; Xing, Jinchuan; Snyder, Michael P.; Jorde, Lynn B.; Batzer, Mark A.; Korbel, Jan O.; Marth, Gabor T.

    2011-01-01

    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations. PMID:21876680

  9. Army Planning: Comprehensive Risk Assessment Needed for Planned Changes to the Armys Force Structure

    DTIC Science & Technology

    2016-04-01

    a new permanent duty station. 13 GAO, Risk Management: Further Refinements Needed to Assess Risks and Prioritize Protective Measures at Ports and...limit the Army’s ability to transport troops around the battlefield, among other risks . The Army intends to add 4 medium truck companies to its...ARMY PLANNING Comprehensive Risk Assessment Needed for Planned Changes to the Army’s Force Structure Report to

  10. The need for comprehensive vulnerability approaches to mirror the multiplicity in mountain hazard risk

    NASA Astrophysics Data System (ADS)

    Keiler, Margreth; Fuchs, Sven

    2014-05-01

    The concept of vulnerability is pillared by multiple disciplinary theories underpinning either a technical or a social origin of the concept and resulting in a range of paradigms for vulnerability quantification. By taking a natural scientific approach we argue that a large number of studies have focused either on damage-loss functions for individual mountain hazards or on semi-quantitative indicator-based approaches for multiple hazards (hazard chains). However, efforts to reduce susceptibility to hazards and to create disaster-resilient communities require intersections among these approaches, as well as among theories originating in natural and social sciences, since human activity cannot be seen independently from the environmental setting. Acknowledging different roots of disciplinary paradigms in risk management, issues determining structural, economic, institutional and social vulnerability have to be more comprehensively addressed in the future with respect to mountain hazards in Europe and beyond. It is argued that structural vulnerability as originator results in considerable economic vulnerability, generated by the institutional settings of dealing with natural hazards and shaped by the overall societal framework. If vulnerability and its counterpart, resilience, is analysed and evaluated by using such a comprehensive approach, a better understanding of the vulnerability-influencing parameters could be achieved, taking into account the interdependencies and interactions between the disciplinary foci. As a result, three key issues should be addressed in future research: (1) Vulnerability requires a new perspective on the relationship between society and environment: not as a duality, but more as a mutually constitutive relationship (including methods for assessment). (2) There is a need for concepts of vulnerability that emphasise the dynamics of temporal and spatial scales, particularly with respect to Global Change processes in mountain regions. (3

  11. Perceived Risk of Breast Cancer among Latinas Attending Community Clinics: Risk Comprehension and Relationship with Mammography Adherence

    PubMed Central

    Graves, Kristi D.; Huerta, Elmer; Cullen, Jennifer; Kaufman, Elizabeth; Sheppard, Vanessa; Luta, George; Isaacs, Claudine; Schwartz, Marc D.; Mandelblatt, Jeanne

    2015-01-01

    Objective To describe breast cancer risk perceptions, determine risk comprehension, and evaluate mammography adherence among Latinas. Methods Latina women age ≥ 35, primarily from Central and South America, were recruited from community-based clinics to complete in-person interviews (n=450). Risk comprehension was calculated as the difference between numeric perceived risk and Gail risk score. Based on recommended guidelines from the year data were collected (2002), mammography adherence was defined as having a mammogram every one to two years for women ≥ 40 years of age. Results Breast cancer risk comprehension was low, as 81% of women overestimated their risk and only 6.9% of women were high risk based on Gail risk scores. Greater cancer worry and younger age were significantly associated with greater perceived risk and risk overestimation. Of women age eligible for mammography (n = 328), 29.0% were non-adherent to screening guidelines. Adherence was associated with older age, (OR = 2.99, 95% CI = 1.76 – 5.09), having insurance (OR = 1.81, 95% CI = 1.03 – 3.17), greater acculturation (OR = 1.18, 95% CI = 1.02 – 1.36), and higher breast cancer knowledge (OR = 2.03, 95% CI = 1.21 – 3.40). Conclusions While most Latinas over-estimated their breast cancer risk, older age, having insurance, being more acculturated, and having greater knowledge were associated with greater screening adherence in this Latino population. Perceived risk, risk comprehension, and cancer worry were not associated with adherence. In Latinas, screening interventions should emphasize knowledge and target education efforts at younger, uninsured, and less acculturated mammography-eligible women. PMID:18704716

  12. A comprehensive quantitative assessment of bird extinction risk in Brazil.

    PubMed

    Machado, Nathália; Loyola, Rafael Dias

    2013-01-01

    In an effort to avoid species loss, scientists have focused their efforts on the mechanisms making some species more prone to extinction than others. However, species show different responses to threats given their evolutionary history, behavior, and intrinsic biological features. We used bird biological features and external threats to (1) understand the multiple pathways driving Brazilian bird species to extinction, (2) to investigate if and how extinction risk is geographically structured, and (3) to quantify how much diversity is currently represented inside protected areas. We modeled the extinction risk of 1557 birds using classification trees and evaluated the relative contribution of each biological feature and external threat in predicting extinction risk. We also quantified the proportion of species and their geographic range currently protected by the network of Brazilian protected areas. The optimal classification tree showed different pathways to bird extinction. Habitat conversion was the most important predictor driving extinction risk though other variables, such as geographic range size, type of habitat, hunting or trapping and trophic guild, were also relevant in our models. Species under higher extinction risk were concentrated mainly in the Cerrado Biodiversity Hotspot and were not quite represented inside protected areas, neither in richness nor range. Predictive models could assist conservation actions, and this study could contribute by highlighting the importance of natural history and ecology in these actions.

  13. A Comprehensive Quantitative Assessment of Bird Extinction Risk in Brazil

    PubMed Central

    Machado, Nathália; Loyola, Rafael Dias

    2013-01-01

    In an effort to avoid species loss, scientists have focused their efforts on the mechanisms making some species more prone to extinction than others. However, species show different responses to threats given their evolutionary history, behavior, and intrinsic biological features. We used bird biological features and external threats to (1) understand the multiple pathways driving Brazilian bird species to extinction, (2) to investigate if and how extinction risk is geographically structured, and (3) to quantify how much diversity is currently represented inside protected areas. We modeled the extinction risk of 1557 birds using classification trees and evaluated the relative contribution of each biological feature and external threat in predicting extinction risk. We also quantified the proportion of species and their geographic range currently protected by the network of Brazilian protected areas. The optimal classification tree showed different pathways to bird extinction. Habitat conversion was the most important predictor driving extinction risk though other variables, such as geographic range size, type of habitat, hunting or trapping and trophic guild, were also relevant in our models. Species under higher extinction risk were concentrated mainly in the Cerrado Biodiversity Hotspot and were not quite represented inside protected areas, neither in richness nor range. Predictive models could assist conservation actions, and this study could contribute by highlighting the importance of natural history and ecology in these actions. PMID:23951302

  14. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-29

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  15. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    PubMed Central

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  16. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-31

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  17. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-12-30

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  18. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

    Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2013-11-22

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  19. Project LINK: Improving Risk and Protective Factors through Comprehensive Services

    ERIC Educational Resources Information Center

    Cross, Jennifer E.; Mohajeri-Nelson, Nazanin; Newman-Gonchar, Rebecca

    2007-01-01

    This article describes the outcomes of Project LINK, a Safe Schools/Healthy Students grantee in Larimer County, Colorado. The study analyzed the influence of policies and administrative support on the implementation of programs as well as on risk and protective factors predictive of violent behaviors and drug and alcohol use. Results showed…

  20. Assessing Human Health Risk from Pesticides

    EPA Pesticide Factsheets

    EPA protects human health and the environment by evaluating the risk associated with pesticides before allowing them to be used in the United States. Learn about the tools and processes used in risk assessment for pesticides.

  1. Reduction in Sexual Risk Behaviors among College Students Following a Comprehensive Health Education Intervention.

    ERIC Educational Resources Information Center

    Turner, James C.; And Others

    1993-01-01

    Researchers studied college students' sexual behavior and the association of a comprehensive health education program with subsequent sexual risk behavior modifications. Pre- and postintervention surveys indicated the intervention created short-term reduction in sexual risk behaviors, but the reduction varied according to gender. (SM)

  2. A Comprehensive Profile of Health Risk Behaviors Among Students at a Small Canadian University

    ERIC Educational Resources Information Center

    Taylor, Jennifer P.; McCarthy, Mary Jean; Herbert, Rosemary J.; Smith, Philip B.

    2009-01-01

    Despite recent attention to health promotion and illness prevention, young people continue to engage in a variety of risk behaviors, which may negatively influence current and future health status. The purpose of this study was to create a comprehensive profile of health risk behaviors among undergraduate students at the University of Prince…

  3. Reduction in Sexual Risk Behaviors among College Students Following a Comprehensive Health Education Intervention.

    ERIC Educational Resources Information Center

    Turner, James C.; And Others

    1993-01-01

    Researchers studied college students' sexual behavior and the association of a comprehensive health education program with subsequent sexual risk behavior modifications. Pre- and postintervention surveys indicated the intervention created short-term reduction in sexual risk behaviors, but the reduction varied according to gender. (SM)

  4. How Numeracy Influences Risk Comprehension and Medical Decision Making

    PubMed Central

    Reyna, Valerie F.; Nelson, Wendy L.; Han, Paul K.; Dieckmann, Nathan F.

    2009-01-01

    We review the growing literature on health numeracy, the ability to understand and use numerical information, and its relation to cognition, health behaviors, and medical outcomes. Despite the surfeit of health information from commercial and noncommercial sources, national and international surveys show that many people lack basic numerical skills that are essential to maintain their health and make informed medical decisions. Low numeracy distorts perceptions of risks and benefits of screening, reduces medication compliance, impedes access to treatments, impairs risk communication (limiting prevention efforts among the most vulnerable), and, based on the scant research conducted on outcomes, appears to adversely affect medical outcomes. Low numeracy is also associated with greater susceptibility to extraneous factors (i.e., factors that do not change the objective numerical information). That is, low numeracy increases susceptibility to effects of mood or how information is presented (e.g., as frequencies vs. percentages) and to biases in judgment and decision making (e.g., framing and ratio bias effects). Much of this research is not grounded in empirically supported theories of numeracy or mathematical cognition, which are crucial for designing evidence-based policies and interventions that are effective in reducing risk and improving medical decision making. To address this gap, we outline four theoretical approaches (psychophysical, computational, standard dual-process, and fuzzy trace theory), review their implications for numeracy, and point to avenues for future research. PMID:19883143

  5. Risk Management for Human Support Technology Development

    NASA Technical Reports Server (NTRS)

    jones, Harry

    2005-01-01

    NASA requires continuous risk management for all programs and projects. The risk management process identifies risks, analyzes their impact, prioritizes them, develops and carries out plans to mitigate or accept them, tracks risks and mitigation plans, and communicates and documents risk information. Project risk management is driven by the project goal and is performed by the entire team. Risk management begins early in the formulation phase with initial risk identification and development of a risk management plan and continues throughout the project life cycle. This paper describes the risk management approach that is suggested for use in NASA's Human Support Technology Development. The first step in risk management is to identify the detailed technical and programmatic risks specific to a project. Each individual risk should be described in detail. The identified risks are summarized in a complete risk list. Risk analysis provides estimates of the likelihood and the qualitative impact of a risk. The likelihood and impact of the risk are used to define its priority location in the risk matrix. The approaches for responding to risk are either to mitigate it by eliminating or reducing the effect or likelihood of a risk, to accept it with a documented rationale and contingency plan, or to research or monitor the risk, The Human Support Technology Development program includes many projects with independently achievable goals. Each project must do independent risk management, considering all its risks together and trading them against performance, budget, and schedule. Since the program can succeed even if some projects fail, the program risk has a complex dependence on the individual project risks.

  6. Risk Management for Human Support Technology Development

    NASA Technical Reports Server (NTRS)

    jones, Harry

    2005-01-01

    NASA requires continuous risk management for all programs and projects. The risk management process identifies risks, analyzes their impact, prioritizes them, develops and carries out plans to mitigate or accept them, tracks risks and mitigation plans, and communicates and documents risk information. Project risk management is driven by the project goal and is performed by the entire team. Risk management begins early in the formulation phase with initial risk identification and development of a risk management plan and continues throughout the project life cycle. This paper describes the risk management approach that is suggested for use in NASA's Human Support Technology Development. The first step in risk management is to identify the detailed technical and programmatic risks specific to a project. Each individual risk should be described in detail. The identified risks are summarized in a complete risk list. Risk analysis provides estimates of the likelihood and the qualitative impact of a risk. The likelihood and impact of the risk are used to define its priority location in the risk matrix. The approaches for responding to risk are either to mitigate it by eliminating or reducing the effect or likelihood of a risk, to accept it with a documented rationale and contingency plan, or to research or monitor the risk, The Human Support Technology Development program includes many projects with independently achievable goals. Each project must do independent risk management, considering all its risks together and trading them against performance, budget, and schedule. Since the program can succeed even if some projects fail, the program risk has a complex dependence on the individual project risks.

  7. Comprehensive Health Risk Management after the Fukushima Nuclear Power Plant Accident.

    PubMed

    Yamashita, S

    2016-04-01

    Five years have passed since the Great East Japan Earthquake and the subsequent Fukushima Daiichi Nuclear Power Plant accident on 11 March 2011. Countermeasures aimed at human protection during the emergency period, including evacuation, sheltering and control of the food chain were implemented in a timely manner by the Japanese Government. However, there is an apparent need for improvement, especially in the areas of nuclear safety and protection, and also in the management of radiation health risk during and even after the accident. Continuous monitoring and characterisation of the levels of radioactivity in the environment and foods in Fukushima are now essential for obtaining informed consent to the decisions on living in the radio-contaminated areas and also on returning back to the evacuated areas once re-entry is allowed; it is also important to carry out a realistic assessment of the radiation doses on the basis of measurements. Until now, various types of radiation health risk management projects and research have been implemented in Fukushima, among which the Fukushima Health Management Survey is the largest health monitoring project. It includes the Basic Survey for the estimation of external radiation doses received during the first 4 months after the accident and four detailed surveys: thyroid ultrasound examination, comprehensive health check-up, mental health and lifestyle survey, and survey on pregnant women and nursing mothers, with the aim to prospectively take care of the health of all the residents of Fukushima Prefecture for a long time. In particular, among evacuees of the Fukushima Nuclear Power Plant accident, concern about radiation risk is associated with psychological stresses. Here, ongoing health risk management will be reviewed, focusing on the difficult challenge of post-disaster recovery and resilience in Fukushima. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. Comprehensive safeguards evaluation methods and societal risk analysis

    SciTech Connect

    Richardson, J.M.

    1982-03-01

    Essential capabilities of an integrated evaluation methodology for analyzing safeguards systems are discussed. Such a methodology must be conceptually meaningful, technically defensible, discriminating and consistent. A decompostion of safeguards systems by function is mentioned as a possible starting point for methodology development. The application of a societal risk equation to safeguards systems analysis is addressed. Conceptual problems with this approach are discussed. Technical difficulties in applying this equation to safeguards systems are illustrated through the use of confidence intervals, information content, hypothesis testing and ranking and selection procedures.

  9. Ultraviolet Radiation: Human Exposure and Health Risks.

    ERIC Educational Resources Information Center

    Tenkate, Thomas D.

    1998-01-01

    Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

  10. Ultraviolet Radiation: Human Exposure and Health Risks.

    ERIC Educational Resources Information Center

    Tenkate, Thomas D.

    1998-01-01

    Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

  11. [Type 2 diabetes mellitus and cardiovascular risk factors: is comprehensive treatment required?].

    PubMed

    Nadal, Josep Franch; Gutiérrez, Pedro Conthe

    2013-09-01

    Diabetes mellitus, especially type 2, is a metabolic disease involving the coexistence of several cardiovascular risk factors. Affected patients are therefore at high cardiovascular risk (2-3 times higher than that of men in the general population and 2-6 times higher than that of women). Cardiovascular disease is the main cause of death in the diabetic population, followed by cancer. Cardiovascular risk cannot be compared between diabetic patients and persons who have already shown one or more manifestations of cardiovascular disease (such as myocardial infarction). Single risk factors should be evaluated in combination with other risk factors and a person's cardiovascular risk should be individually assessed. Cardiovascular risk assessment in patients with diabetes through current calculations methods is complex because their ability to predict risk in individuals is very low. Studies such as that by Steno have demonstrated the validity of a comprehensive strategy to control all the risk factors present in persons with type 2 diabetes mellitus, which can reduce the development of micro- and macrovascular complications and mortality by almost 50%. The present article reviews each of the classical cardiovascular risk factors (hypertension, dyslipidemia, smoking, obesity, sedentariness) in relation to diabetes, as well as their recommended targets and the benefits of their control. In view of the above, a comprehensive approach is recommended to control the multiple risk factors that can coexist in persons with type 2 diabetes mellitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Comprehensive serological profiling of human populations using a synthetic human virome

    PubMed Central

    Xu, George J.; Kula, Tomasz; Xu, Qikai; Li, Mamie Z.; Vernon, Suzanne D.; Ndung’u, Thumbi; Ruxrungtham, Kiat; Sanchez, Jorge; Brander, Christian; Chung, Raymond T.; O’Connor, Kevin C.; Walker, Bruce; Larman, H. Benjamin; Elledge, Stephen J.

    2016-01-01

    The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 108 antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strikingly conserved “public epitopes” for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system. PMID:26045439

  13. Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome.

    PubMed

    Xu, George J; Kula, Tomasz; Xu, Qikai; Li, Mamie Z; Vernon, Suzanne D; Ndung'u, Thumbi; Ruxrungtham, Kiat; Sanchez, Jorge; Brander, Christian; Chung, Raymond T; O'Connor, Kevin C; Walker, Bruce; Larman, H Benjamin; Elledge, Stephen J

    2015-06-05

    The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10(8) antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved "public epitopes" for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system. Copyright © 2015, American Association for the Advancement of Science.

  14. Fuzzy Comprehensive Evaluation Method Applied in the Real Estate Investment Risks Research

    NASA Astrophysics Data System (ADS)

    ML(Zhang Minli), Zhang; Wp(Yang Wenpo), Yang

    Real estate investment is a high-risk and high returned of economic activity, the key of real estate analysis is the identification of their types of investment risk and the risk of different types of effective prevention. But, as the financial crisis sweeping the world, the real estate industry also faces enormous risks, how effective and correct evaluation of real estate investment risks becomes the multitudinous scholar concern[1]. In this paper, real estate investment risks were summarized and analyzed, and comparative analysis method is discussed and finally presented fuzzy comprehensive evaluation method, not only in theory has the advantages of science, in the application also has the reliability, for real estate investment risk assessment provides an effective means for investors in real estate investing guidance on risk factors and forecasts.

  15. Comprehensive comparison of neonate and adult human platelet transcriptomes

    PubMed Central

    Caparrós-Pérez, Eva; López-Andreo, Mª José; Llanos, Mª Carmen; Rivera, José; Palma-Barqueros, Verónica; Blanco, Jose E.; Vicente, Vicente; Martínez, Constantino; Ferrer-Marín, Francisca

    2017-01-01

    Understanding the underlying mechanisms of the well-substantiated platelet hyporeactivity in neonates is of interest given their implications for the clinical management of newborns, a population at higher bleeding risk than adults (especially sick and preterm infants), as well as for gaining insight into the regulatory mechanisms of platelet biology. Transcriptome analysis is useful in identifying mRNA signatures affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never before been reported. We have used mRNA expression array for the first time to compare platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories. A high correlation was obtained between array results for both adult and neonate platelet samples. There was also good agreement between results in our adult samples and outcomes previously reported in three different studies. Gene enrichment analysis showed that immunity- and platelet function-related genes are highly expressed at both developmental stages. Remarkably, 201 genes were found to be differentially expressed throughout development. In particular, neonatal platelets contain higher levels of mRNA that are associated with protein synthesis and processing, while carrying significantly lower levels of genes involved in calcium transport/metabolism and cell signaling (including GNAZ). Overall, our results point to variations in platelet transcriptome as possibly underlining the hypo-functional phenotype of neonatal platelets and provide further support for the role of platelets in cellular immune response. Better characterization of the platelet transcriptome throughout development can contribute to elucidate how transcriptome changes impact different pathological conditions. PMID:28813466

  16. State high-risk pools: an update on the Minnesota Comprehensive Health Association.

    PubMed

    Blewett, Lynn A; Spencer, Donna; Burke, Courtney E

    2011-02-01

    State health insurance high-risk pools are a key component of the US health care system's safety net, because they provide health insurance to the "uninsurable." In 2007, 34 states had individual high-risk pools, which covered more than 200 000 people at a total cost of $1.8 billion. We examine the experience of the largest and oldest pool in the nation, the Minnesota Comprehensive Health Association, to document key issues facing state high-risk pools in enrollment and financing. We also considered the role and future of high-risk pools in light of national health care finance reform.

  17. Integrating Spaceflight Human System Risk Research

    NASA Technical Reports Server (NTRS)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2016-01-01

    NASA is working to increase the likelihood of human health and performance success during exploration missions as well as to maintain the subsequent long-term health of the crew. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. "Human System Risks" (Risks) have been identified, and approximately 30 are being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  18. Integrating Spaceflight Human System Risk Research

    NASA Technical Reports Server (NTRS)

    Mindock, J.; Lumpkins, S.; Anton, W.; Havenhill, M.; Shelhamer, M.; Canga, M.

    2016-01-01

    NASA is working to increase the likelihoods of human health and performance success during exploration missions, and subsequent crew long-term health. To manage the risks in achieving these goals, a system modeled after a Continuous Risk Management framework is in place. "Human System Risks" (Risks) have been identified, and approximately 30 are being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Ties between the research efforts supporting each Risk have been identified, however, this has been in an ad hoc fashion. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioral, vehicle, and organizational aspects of the exploration missions must be integrated across Risks and disciplines. We will discuss how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information is allowing us to identify and visualize connections between Risks and research efforts in a systematic and standardized way. We will discuss the applications of the visualizations and insights to research planning, solicitation, and decision-making processes.

  19. The spatial distribution characteristics of a comprehensive drought risk index in southwestern China and underlying causes

    NASA Astrophysics Data System (ADS)

    Han, Lanying; Zhang, Qiang; Ma, Pengli; Jia, Jianying; Wang, Jinsong

    2016-05-01

    Drought is a serious problem in southwestern China, where drought risk exceeds the national average. Climate change is likely to exacerbate the problem, thereby endangering China's food security. In this paper, we used the analytic hierarchy process and meteorological, geographic, soil, and remote-sensing data to develop a drought risk assessment model based on the drought hazard, environmental vulnerability, sensitivity and exposure of the values at risk, and capacity to prevent or mitigate the problem. Using the model, we assessed the drought risk (defined using a comprehensive drought risk index, R) and its spatial distribution in southwestern China and revealed complex zonality. The eastern part of the study area had an extremely high risk, and risk was generally greater in the north than in the south, and increased from southwest to northeast. The comprehensive risk ( R) was lowest in Yunnan province. It was highest in Sichuan Province and Chongqing Municipality. The contribution of the risk factors to R was highest for the capacity for prevention and mitigation, followed by the drought hazard, sensitivity and exposure, and environmental vulnerability.

  20. Reading Comprehension Difficulties among Students with Disabilities and Students At-Risk

    ERIC Educational Resources Information Center

    Blinkhorn, Donna L.

    2009-01-01

    The quantitative method and quasi-experimental design examined the effects of multimodal-multisensory instructional strategies (MMIS) on vocabulary acquisition and reading comprehension among students at-risk and students with disabilities in an inclusive environment. To discover the efficacy of multimodal-multisensory instructional strategies,…

  1. Developing a Comprehensive Approach Could Help DOD Better Manage National Security Risks in the Supply Chain

    DTIC Science & Technology

    2016-02-01

    RARE EARTH MATERIALS Developing a Comprehensive Approach Could Help DOD Better Manage National Security Risks in...States Government Accountability Office Highlights of GAO-16-161, a report to congressional committees February 2016 RARE EARTH MATERIALS...rare earths that contain one or more of 17 similar metals which have unique properties, such as magnetism at high temperatures, to provide

  2. Problems in Comprehensive Ambulatory Health Care for High-Risk Adolescents.

    ERIC Educational Resources Information Center

    Fielding, Jon E., Ed.

    This volume contains 21 articles on aspects held to be important for delivering comprehensive health care to young adults who are at higher than average risk levels for a number of health and health-related problems; choice of topics for the articles is based on experience gained in directing the health program for the Job Corps. Most of the…

  3. Effects of Comprehensive, Multiple High-Risk Behaviors Prevention Program on High School Students

    ERIC Educational Resources Information Center

    Collier, Crystal

    2013-01-01

    The purpose of this mixed methods study was to examine the effect of a multiple high-risk behaviors prevention program applied comprehensively throughout an entire school-system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The prevention program was created based upon the…

  4. Supporting nanomaterial risk assessment by case studies of nano-titanium dioxide using comprehensive environmental assessment

    EPA Science Inventory

    Here we describe a comprehensive environmental assessment (CEA) approach for two case studies of nano-titanium dioxide (nano-TiO2) in real world applications: water treatment and sunscreen. CEA combines a product life cycle framework with the risk assessment paradigm.

  5. Effects of Comprehensive, Multiple High-Risk Behaviors Prevention Program on High School Students

    ERIC Educational Resources Information Center

    Collier, Crystal

    2013-01-01

    The purpose of this mixed methods study was to examine the effect of a multiple high-risk behaviors prevention program applied comprehensively throughout an entire school-system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The prevention program was created based upon the…

  6. Promoting Teacher Change To Enhance Comprehension for At-Risk Students.

    ERIC Educational Resources Information Center

    Block, Cathy Collins; Gasser, Judy

    A study examined shifts that occur in teachers' behaviors and teaching repertoires as they become more strategic teachers, and the types of instruction that lead to the greatest growth in at-risk students' comprehension and reading abilities. A literacy initiative coordinator and a college researcher worked collaboratively with nine teachers to…

  7. Supporting nanomaterial risk assessment by case studies of nano-titanium dioxide using comprehensive environmental assessment

    EPA Science Inventory

    Here we describe a comprehensive environmental assessment (CEA) approach for two case studies of nano-titanium dioxide (nano-TiO2) in real world applications: water treatment and sunscreen. CEA combines a product life cycle framework with the risk assessment paradigm.

  8. Adolescent views on comprehensive health risk assessment and counseling: assessing gender differences.

    PubMed

    Kadivar, Hajar; Thompson, Lindsay; Wegman, Martin; Chisholm, TaJuana; Khan, Maryum; Eddleton, Katie; Muszynski, Michael; Shenkman, Elizabeth

    2014-07-01

    Adolescence is an important time for the detection of health risk behaviors and factors with subsequent counseling and intervention. Limited research has examined adolescent perceptions of comprehensive health risk assessments (HRAs) and counseling with an assessment of gender differences. Participants were identified using Florida's Medicaid and State Children's Health Insurance Program databases. A total of 35 low-income, racially/ethnically diverse adolescents (ages 14-18 years) participated in eight focus groups stratified by gender. Adolescents completed an internet-based, tablet-administered, comprehensive HRA and then participated in a semi-structured interview. Discussions were recorded, transcribed, and analyzed using a multi-step, team-based approach applying grounded theory to determine major themes. Male adolescents desired less parental involvement, had less understanding of the protections of clinical confidentiality and the need for comprehensive HRA, and placed greater emphasis on the importance of professional appearance. In contrast, more females valued face-to-face interactions and stressed the importance of concern from the health risk assessor. Overall, adolescents placed importance on their relationship with the health risk assessor, and on valuing trust, confidentiality, and nonjudgmental care. Adolescents preferred to complete HRAs in clinical, private, and professional settings, and reported that tablet technology supported their confidentially in completing the HRA. Furthermore, they stressed the importance of autonomy and learning about the health risk outcomes for risk reduction. Gender differences exist in adolescent perceptions of comprehensive HRAs. Adolescent perceptions of HRAs support their use in confidential primary care settings using modalities that emphasize nonjudgmental, private care, and the use of communication techniques that respect adolescents' autonomy to change health risks. Copyright © 2014. Published by Elsevier

  9. Revised Human Health Risk Assessment on Chlorpyrifos

    EPA Pesticide Factsheets

    We have revised our human health risk assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos. Learn about the revised analysis.

  10. Integrating spaceflight human system risk research

    NASA Astrophysics Data System (ADS)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2017-10-01

    NASA is working to increase the likelihood of exploration mission success and to maintain crew health, both during exploration missions and long term after return to Earth. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. ;Human System Risks; (Risks) have been identified, and 32 are currently being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  11. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters

    PubMed Central

    Aagaard, Kjersti; Petrosino, Joseph; Keitel, Wendy; Watson, Mark; Katancik, James; Garcia, Nathalia; Patel, Shital; Cutting, Mary; Madden, Tessa; Hamilton, Holli; Harris, Emily; Gevers, Dirk; Simone, Gina; McInnes, Pamela; Versalovic, James

    2013-01-01

    The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m2, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.—Aagaard, K., Petrosino, J., Keitel, W., Watson, M., Katancik, J., Garcia, N., Patel, S., Cutting, M., Madden, T., Hamilton, H., Harris, E., Gevers, D., Simone, G., McInnes, P., Versalovic, J. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. PMID:23165986

  12. Women at Risk for Human Immunodeficiency Virus.

    ERIC Educational Resources Information Center

    Quadagno, David; And Others

    This article reports results from a survey among women at risk for contracting Human Immunodeficiency Virus (HIV) as well as transmitting it in a vertical (to offspring) and horizontal (sexual partner or intravenous [IV] drug usage) mode. Little is known about the extent of HIV knowledge, sexual behaviors, and IV drug usage for women at risk for…

  13. Women at Risk for Human Immunodeficiency Virus.

    ERIC Educational Resources Information Center

    Quadagno, David; And Others

    This article reports results from a survey among women at risk for contracting Human Immunodeficiency Virus (HIV) as well as transmitting it in a vertical (to offspring) and horizontal (sexual partner or intravenous [IV] drug usage) mode. Little is known about the extent of HIV knowledge, sexual behaviors, and IV drug usage for women at risk for…

  14. A comprehensive repertoire of prokaryotic species identified in human beings.

    PubMed

    Hugon, Perrine; Dufour, Jean-Charles; Colson, Philippe; Fournier, Pierre-Edouard; Sallah, Kankoe; Raoult, Didier

    2015-10-01

    The compilation of the complete prokaryotic repertoire associated with human beings as commensals or pathogens is a major goal for the scientific and medical community. The use of bacterial culture techniques remains a crucial step to describe new prokaryotic species. The large number of officially acknowledged bacterial species described since 1980 and the recent increase in the number of recognised pathogenic species have highlighted the absence of an exhaustive compilation of species isolated in human beings. By means of a thorough investigation of several large culture databases and a search of the scientific literature, we built an online database containing all human-associated prokaryotic species described, whether or not they had been validated and have standing in nomenclature. We list 2172 species that have been isolated in human beings. They were classified in 12 different phyla, mostly in the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Our online database is useful for both clinicians and microbiologists and forms part of the Human Microbiome Project, which aims to characterise the whole human microbiota and help improve our understanding of the human predisposition and susceptibility to infectious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Towards a comprehensive assessment and framework for low and high flow water risks

    NASA Astrophysics Data System (ADS)

    Motschmann, Alina; Huggel, Christian; Drenkhan, Fabian; León, Christian

    2017-04-01

    Driven by international organizations such as the Intergovernmental Panel on Climate Change (IPCC) the past years have seen a move from a vulnerability concept of climate change impacts towards a risk framework. Risk is now conceived at the intersection of climate-driven hazard and socioeconomic-driven vulnerability and exposure. The concept of risk so far has been mainly adopted for sudden-onset events. However, for slow-onset and cumulative climate change impacts such as changing water resources there is missing clarity and experience how to apply a risk framework. Research has hardly dealt with the challenge of how to integrate both low and high flow risks in a common framework. Comprehensive analyses of risks related to water resources considering climate change within multi-dimensional drivers across different scales are complex and often missing in climate-sensitive mountain regions where data scarcity and inconsistencies represent important limitations. Here we review existing vulnerability and risk assessments of low and high flow water conditions and identify critical conceptual and practical gaps. Based on this, we develop an integrated framework for low and high flow water risks which is applicable to both past and future conditions. The framework explicitly considers a water balance model simulating both water supply and demand on a daily basis. We test and apply this new framework in the highly glacierized Santa River catchment (SRC, Cordillera Blanca, Peru), representative for many developing mountain regions with both low and high flow water risks and poor data availability. In fact, in the SRC, both low and high flow hazards, such as droughts and floods, play a central role especially for agricultural, hydropower, domestic and mining use. During the dry season (austral winter) people are increasingly affected by water scarcity due to shrinking glaciers supplying melt water. On the other hand during the wet season (austral summer) high flow water

  16. TOXICOGENOMICS AND HUMAN DISEASE RISK ASSESSMENT

    EPA Science Inventory


    Toxicogenomics and Human Disease Risk Assessment.

    Complete sequencing of human and other genomes, availability of large-scale gene
    expression arrays with ever-increasing numbers of genes displayed, and steady
    improvements in protein expression technology can hav...

  17. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  18. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  19. Comprehensive analysis of microorganisms accompanying human archaeological remains.

    PubMed

    Philips, Anna; Stolarek, Ireneusz; Kuczkowska, Bogna; Juras, Anna; Handschuh, Luiza; Piontek, Janusz; Kozlowski, Piotr; Figlerowicz, Marek

    2017-07-01

    Metagenome analysis has become a common source of information about microbial communities that occupy a wide range of niches, including archaeological specimens. It has been shown that the vast majority of DNA extracted from ancient samples come from bacteria (presumably modern contaminants). However, characterization of microbial DNA accompanying human remains has never been done systematically for a wide range of different samples. We used metagenomic approaches to perform comparative analyses of microorganism communities present in 161 archaeological human remains. DNA samples were isolated from the teeth of human skeletons dated from 100 AD to 1200 AD. The skeletons were collected from 7 archaeological sites in Central Europe and stored under different conditions. The majority of identified microbes were ubiquitous environmental bacteria that most likely contaminated the host remains not long ago. We observed that the composition of microbial communities was sample-specific and not correlated with its temporal or geographical origin. Additionally, traces of bacteria and archaea typical for human oral/gut flora, as well as potential pathogens, were identified in two-thirds of the samples. The genetic material of human-related species, in contrast to the environmental species that accounted for the majority of identified bacteria, displayed DNA damage patterns comparable with endogenous human ancient DNA, which suggested that these microbes might have accompanied the individual before death. Our study showed that the microbiome observed in an individual sample is not reliant on the method or duration of sample storage. Moreover, shallow sequencing of DNA extracted from ancient specimens and subsequent bioinformatics analysis allowed both the identification of ancient microbial species, including potential pathogens, and their differentiation from contemporary species that colonized human remains more recently. © The Authors 2017. Published by Oxford University

  20. Long Duration Space Missions: Human Subsystem Risks and Requirements

    NASA Technical Reports Server (NTRS)

    Kundrot, Criag E.

    2011-01-01

    This viewgraph presentation reviews the human health and performance risks associated with long duration space flight beyond low earth orbit. The contents include: 1) Human Research Program; 2) Human Subsystem Risks; 3) Human Exploration Framework Team (HEFT) Architecture Elements; 4) Potentially Unacceptable Risks -1; 5) Potentially Unacceptable Risks-2; and 6) Major Mission Drivers of Risk.

  1. A comprehensive analysis of MRI research risks: in support of full disclosure.

    PubMed

    Marshall, Jennifer; Martin, Toby; Downie, Jocelyn; Malisza, Krisztina

    2007-02-01

    Magnetic resonance imaging (MRI) procedures have been used for over 20 years. This modality is considered relatively safe and holds great promise. Yet, MRI has a number of risks. In order for MRI research to meet the Canadian standard of disclosure, the investigator must communicate and make note of all risks in their research protocols and consent forms. Those creating and reviewing research protocols and consent forms must take notice of the different circumstances under which MRI poses a risk. First, this paper will describe the current standard of disclosure in Canada for research participants. Second, the paper will provide a comprehensive synthesis of the known physical and psychological risks associated with MRI. Third, the paper will provide recommendations concerning areas for further investigation and risk reduction strategies. This information will thus equip researchers and research ethics boards (REBs) with the criteria needed for the composition of research protocols that meet the Canadian disclosure standard.

  2. Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

    PubMed

    Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

    2016-04-01

    As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

  3. Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation.

    PubMed

    Li, Maozhong; Du, Yunai; Wang, Qiyue; Sun, Chunmeng; Ling, Xiang; Yu, Boyang; Tu, Jiasheng; Xiong, Yerong

    2016-01-01

    As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.

  4. Risk Stratification Methods and Provision of Care Management Services in Comprehensive Primary Care Initiative Practices.

    PubMed

    Reddy, Ashok; Sessums, Laura; Gupta, Reshma; Jin, Janel; Day, Tim; Finke, Bruce; Bitton, Asaf

    2017-09-01

    Risk-stratified care management is essential to improving population health in primary care settings, but evidence is limited on the type of risk stratification method and its association with care management services. We describe risk stratification patterns and association with care management services for primary care practices in the Comprehensive Primary Care (CPC) initiative. We undertook a qualitative approach to categorize risk stratification methods being used by CPC practices and tested whether these stratification methods were associated with delivery of care management services. CPC practices reported using 4 primary methods to stratify risk for their patient populations: a practice-developed algorithm (n = 215), the American Academy of Family Physicians' clinical algorithm (n = 155), payer claims and electronic health records (n = 62), and clinical intuition (n = 52). CPC practices using practice-developed algorithm identified the most number of high-risk patients per primary care physician (282 patients, P = .006). CPC practices using clinical intuition had the most high-risk patients in care management and a greater proportion of high-risk patients receiving care management per primary care physician (91 patients and 48%, P =.036 and P =.128, respectively). CPC practices used 4 primary methods to identify high-risk patients. Although practices that developed their own algorithm identified the greatest number of high-risk patients, practices that used clinical intuition connected the greatest proportion of patients to care management services. © 2017 Annals of Family Medicine, Inc.

  5. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1988-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:3368330

  6. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1987-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:3575113

  7. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1989-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:2654889

  8. A comprehensive list of cloned human DNA sequences—1990 update

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1991-01-01

    An updated list of DNA sequences cloned from the human genome over the past year (1990) is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising both gene and pseudogene sequences. PMID:2041801

  9. A comprehensive list of cloned human DNA sequences

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1990-01-01

    A list of DNA sequences cloned from the human genome is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic clones comprising gene and pseudogene sequences, uncharacterised DNA segments and repetitive DNA elements. PMID:2333227

  10. A comprehensive list of cloned human DNA sequences—1991 update

    PubMed Central

    Schmidtke, Jörg; Cooper, David N.

    1992-01-01

    An updated list of DNA sequences cloned from the human genome over the past year (1991) is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic probes comprising both gene and pseudogene sequences. PMID:1598240

  11. Comprehensively Assessing Cognitive and Behavioral Risks for HIV Infection among Middle-Aged and Older Adults

    ERIC Educational Resources Information Center

    Paniagua, Freddy A.; O'Boyle, Michael

    2008-01-01

    A comprehensive survey of HIV/AIDS with middle-aged and older adults should include six domains (e.g., factual knowledge regarding the acquisition and transmission of HIV, traditionally-accepted behavioral risks for HIV infection). A sample of 23 women (54.8%) and 19 men (45.2%), ranging in age from 51 to 85 were surveyed across such domains.…

  12. Comprehensively Assessing Cognitive and Behavioral Risks for HIV Infection among Middle-Aged and Older Adults

    ERIC Educational Resources Information Center

    Paniagua, Freddy A.; O'Boyle, Michael

    2008-01-01

    A comprehensive survey of HIV/AIDS with middle-aged and older adults should include six domains (e.g., factual knowledge regarding the acquisition and transmission of HIV, traditionally-accepted behavioral risks for HIV infection). A sample of 23 women (54.8%) and 19 men (45.2%), ranging in age from 51 to 85 were surveyed across such domains.…

  13. Retinopathy of prematurity: A comprehensive risk analysis for prevention and prediction of disease

    PubMed Central

    Owen, Leah A.; Morrison, Margaux A.; Hoffman, Robert O.; Yoder, Bradley A.; DeAngelis, Margaret M.

    2017-01-01

    Background Retinopathy of prematurity (ROP) is a blinding morbidity of preterm infants. Our current screening criteria have remained unchanged since their inception and lack the ability to identify those at greatest risk. Objectives We sought to comprehensively analyze numerous proposed maternal, infant, and environmental ROP risk variables in a robustly phenotyped population using logistic regression to determine the most predictive model for ROP development and severity. We further sought to determine the statistical interaction between significant ROP risk variables, which has not previously been done in the field of ROP. We hypothesize that our comprehensive analysis will allow for better identification of risk variables that independently correlate with ROP disease. Going forward, this may allow for improved infant risk stratification along a time continuum from prenatal to postnatal development, making prevention more feasible. Methods We performed a retrospective cohort analysis of preterm infants referred for ROP screening in one neonatal intensive care unit from 2010–2015. The primary outcome measure was presence of ROP. Secondary outcome measures were ROP requiring treatment and severe ROP not clearly meeting current treatment criteria. Univariate, stepwise regression and statistical interaction analyses of 57 proposed ROP risk variables was performed to identify variables which were significantly associated with each outcome measure. Results We identified 457 infants meeting our inclusion criteria. Within this cohort, numerous factors showed a significant individual association with our ROP outcome measures; however, stepwise regression analysis found the most predictive model for overall ROP risk included estimated gestational age, birth weight, the need for any surgery, and maternal magnesium prophylaxis. The corresponding Area Under the Curve (AUC) for this model was 0.8641, while the traditional model of gestational age and birth weight predicted

  14. Risk assessment of groundwater contamination: a multilevel fuzzy comprehensive evaluation approach based on DRASTIC model.

    PubMed

    Zhang, Qiuwen; Yang, Xiaohong; Zhang, Yan; Zhong, Ming

    2013-01-01

    Groundwater contamination is a serious threat to water supply. Risk assessment of groundwater contamination is an effective way to protect the safety of groundwater resource. Groundwater is a complex and fuzzy system with many uncertainties, which is impacted by different geological and hydrological factors. In order to deal with the uncertainty in the risk assessment of groundwater contamination, we propose an approach with analysis hierarchy process and fuzzy comprehensive evaluation integrated together. Firstly, the risk factors of groundwater contamination are identified by the sources-pathway-receptor-consequence method, and a corresponding index system of risk assessment based on DRASTIC model is established. Due to the complexity in the process of transitions between the possible pollution risks and the uncertainties of factors, the method of analysis hierarchy process is applied to determine the weights of each factor, and the fuzzy sets theory is adopted to calculate the membership degrees of each factor. Finally, a case study is presented to illustrate and test this methodology. It is concluded that the proposed approach integrates the advantages of both analysis hierarchy process and fuzzy comprehensive evaluation, which provides a more flexible and reliable way to deal with the linguistic uncertainty and mechanism uncertainty in groundwater contamination without losing important information.

  15. Risk Assessment of Groundwater Contamination: A Multilevel Fuzzy Comprehensive Evaluation Approach Based on DRASTIC Model

    PubMed Central

    Zhang, Yan; Zhong, Ming

    2013-01-01

    Groundwater contamination is a serious threat to water supply. Risk assessment of groundwater contamination is an effective way to protect the safety of groundwater resource. Groundwater is a complex and fuzzy system with many uncertainties, which is impacted by different geological and hydrological factors. In order to deal with the uncertainty in the risk assessment of groundwater contamination, we propose an approach with analysis hierarchy process and fuzzy comprehensive evaluation integrated together. Firstly, the risk factors of groundwater contamination are identified by the sources-pathway-receptor-consequence method, and a corresponding index system of risk assessment based on DRASTIC model is established. Due to the complexity in the process of transitions between the possible pollution risks and the uncertainties of factors, the method of analysis hierarchy process is applied to determine the weights of each factor, and the fuzzy sets theory is adopted to calculate the membership degrees of each factor. Finally, a case study is presented to illustrate and test this methodology. It is concluded that the proposed approach integrates the advantages of both analysis hierarchy process and fuzzy comprehensive evaluation, which provides a more flexible and reliable way to deal with the linguistic uncertainty and mechanism uncertainty in groundwater contamination without losing important information. PMID:24453883

  16. Periodontal risk and recall interval evaluation after a program of comprehensive supragingival plaque control.

    PubMed

    Butze, Juliane Pereira; Angst, Patrícia Daniela Melchiors; Oppermann, Rui Vicente; Gomes, Sabrina Carvalho

    2015-10-01

    To investigate if a comprehensive supragingival control can modify the periodontal risk and suggested recall interval over time, using an adaptation of an available model of periodontal risk assessment (PRA, Perio-Tools® website). Single-arm clinical trial data (visible plaque and gingival bleeding indexes, periodontal probing depth, bleeding on probing, and clinical attachment level from baseline (day 0, T0), day 30 (T1), and day 180 (T2) from 50 moderate-to-severe periodontitis patients (25 never-smokers; 25 smokers) submitted to a comprehensive supragingival plaque control regimen for 180 days were subjected to a secondary analysis using an adaptation of the PRA. The periodontal risk (high, medium, or low) and suggested recall interval were calculated per patient and at each experimental time. General linear models and the Cochran test were used for statistical analysis, considering the dependence of the data. All patients were at high risk at baseline. At T1, 20% migrated to medium-risk (P = .002). At T2, 38% and 8% exhibited medium- and low-risk, respectively (P ≤ .001). The reduction between T1 and T2 was significant (P = .001). The mean recall interval increased from 3.0 ± 0.0 (T0) to 3.6 ± 1.2 (T1), and 4.9 ± 2.6 months at T2 (P < .003). The effect that smoking habit exerted on risk was limited to the first 30 days, and no effect on recall interval was observed. The oral hygiene condition is an important indicator that influences the risk and the recall interval over time, thus deserving attention when evaluating the individual periodontal prognosis.

  17. Comprehensive DNA methylation and hydroxymethylation analysis in the human brain and its implication in mental disorders.

    PubMed

    Kato, Tadafumi; Iwamoto, Kazuya

    2014-05-01

    Covalent modifications of nucleotides, such as methylation or hydroxymethylation of cytosine, regulate gene expression. Early environmental risk factors play a role in mental disorders in adulthood. This may be in part mediated by epigenetic DNA modifications. Methods for comprehensive analysis of DNA methylation and hydroxymethylation include DNA modification methods such as bisulfite sequencing, or collection of methylated, hydroxymethylated, or unmethylated DNA by specific binding proteins, antibodies, or restriction enzymes, followed by sequencing or microarray analysis. Results from these experiments should be interpreted with caution because each method gives different result. Cytosine hydroxymethylation has different effects on gene expression than cytosine methylation; methylation of CpG islands is associated with lower gene expression, whereas hydroxymethylation in intragenic regions is associated with higher gene expression. The role of hydroxymethylcytosine is of particular interest in mental disorders because the modification is enriched in the brain and synapse related genes, and it exhibits dynamic regulation during development. Many DNA methylation patterns are conserved across species, but there are also human specific signatures. Comprehensive analysis of DNA methylation shows characteristic changes associated with tissues, brain regions, cell types, and developmental states. Thus, differences in DNA methylation status between tissues, brain regions, cell types, and developmental stages should be considered when the role of DNA methylation in mental disorders is studied. Several disease-associated changes in methylation have been reported: hypermethylation of SOX10 in schizophrenia, hypomethylation of HCG9 (HLA complex group 9) in bipolar disorder, hypermethylation of PRIMA1, hypermethylation of SLC6A4 (serotonin transporter) in bipolar disorder, and hypomethylation of ST6GALNAC1 in bipolar disorder. These findings need to be replicated in

  18. Comprehensive genomic characterization defines human glioblastoma genes and core pathways

    PubMed Central

    2008-01-01

    Human cancer cells typically harbor multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multidimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here, we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas (GBM), the most common type of adult brain cancer, and nucleotide sequence aberrations in 91 of the 206 GBMs. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the PI3 kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of GBM. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer. PMID:18772890

  19. Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

    PubMed

    2008-10-23

    Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

  20. Comprehensive characterization of the genomic alterations in human gastric cancer

    PubMed Central

    Cui, Juan; Yin, Yanbin; Ma, Qin; Wang, Guoqing; Olman, Victor; Zhang, Yu; Chou, Wen-Chi; Hong, Celine S.; Zhang, Chi; Cao, Sha; Mao, Xizeng; Li, Ying; Qin, Steve; Zhao, Shaying; Jiang, Jing; Hastings, Phil; Li, Fan; Xu, Ying

    2016-01-01

    Gastric cancer is one of the most prevalent and aggressive cancers worldwide, and its molecular mechanism remains largely elusive. Here we report the genomic landscape in primary gastric adenocarcinoma of human, based on the complete genome sequences of five pairs of cancer and matching normal samples. In total, 103,464 somatic point mutations, including 407 nonsynonymous ones, were identified and the most recurrent mutations were harbored by Mucins (MUC3A and MUC12) and transcription factors (ZNF717, ZNF595 and TP53). 679 genomic rearrangements were detected, which affect 355 protein-coding genes; and 76 genes show copy number changes. Through mapping the boundaries of the rearranged regions to the folded three-dimensional structure of human chromosomes, we determined that 79.6% of the chromosomal rearrangements happen among DNA fragments in close spatial proximity, especially when two endpoints stay in a similar replication phase. We demonstrated evidences that microhomology-mediated break-induced replication was utilized as a mechanism in inducing ~40.9% of the identified genomic changes in gastric tumor. Our data analyses revealed potential integrations of Helicobacter pylori DNA into the gastric cancer genomes. Overall a large set of novel genomic variations were detected in these gastric cancer genomes, which may be essential to the study of the genetic basis and molecular mechanism of the gastric tumorigenesis. PMID:25422082

  1. Molecular genetics of human obesity: A comprehensive review.

    PubMed

    Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

    2017-02-01

    Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  2. Impact of a comprehensive worksite wellness program on health risk, utilization, and health care costs.

    PubMed

    Hochart, Cindy; Lang, Michelle

    2011-06-01

    In 2005, Blue Cross Blue Shield of Kansas City initiated a comprehensive worksite wellness program designed to impact employer culture and to assist healthy employees to stay at low risk and to reduce risk levels for those at moderate or high risk. Fifteen employer groups (9637 employees) participated in the A Healthier You (AHY) program for 3 consecutive years, 2006-2008. The results of health risk appraisals and biometric screening were used to evaluate program impact. Among the 4230 employees (44.0% of eligible employees) who completed health risk appraisals in all 3 years, 85.8% of individuals in the low-risk category in 2006 remained at low risk in 2008. There were also improvements in other risk categories, with 39.9% of those in the medium-risk category and 48.9% of those in the high-risk category in 2006 moving to a lower risk category in 2008. There were improvements in blood pressure control and total cholesterol, but no improvement in weight control. To assess financial and utilization outcomes, claims for the participating employer groups were compared to those for 7 employers (3800 employees) who did not participate in AHY in 2006-2008. Although none of the utilization measures was statistically different, the AHY groups had significantly smaller increases in both overall and emergency room costs per member per month. The AHY program now has over 180 employer groups, which will allow future evaluations to examine the impact of the program on a much larger population and to focus on the comparative effectiveness of different intervention strategies across implementations.

  3. Toxicological Risks During Human Space Exploration

    NASA Technical Reports Server (NTRS)

    James, John T.; Limero, T. F.; Lam, C. W.; Billica, Roger (Technical Monitor)

    2000-01-01

    The goal of toxicological risk assessment of human space flight is to identify and quantify significant risks to astronaut health from air pollution inside the vehicle or habitat, and to develop a strategy for control of those risks. The approach to completing a toxicological risk assessment involves data and experience on the frequency and severity of toxicological incidents that have occurred during space flight. Control of these incidents depends on being able to understand their cause from in-flight and ground-based analysis of air samples, crew reports of air quality, and known failures in containment of toxic chemicals. Toxicological risk assessment in exploration missions must be based on an evaluation of the unique toxic hazards presented by the habitat location. For example, lunar and Martian dust must be toxicologically evaluated to determine the appropriate control measures for exploration missions. Experience with near-earth flights has shown that the toxic products from fires present the highest risk to crew health from air pollution. Systems and payload leaks also present a significant hazard. The health risk from toxicity associated with materials offgassing or accumulation of human metabolites is generally well controlled. Early tests of lunar and Martian dust simulants have shown that each posses the potential to cause fibrosis in the lung in a murine model. Toxicological risks from air pollutants in space habitats originate from many sources. A number of risks have been identified through near-earth operations; however, the evaluation of additional new risks present during exploration missions will be a challenge.

  4. A Comprehensive Survey of Human Y-Chromosomal Microsatellites

    PubMed Central

    Kayser, Manfred ; Kittler, Ralf ; Erler, Axel ; Hedman, Minttu ; Lee, Andrew C. ; Mohyuddin, Aisha ; Mehdi, S. Qasim ; Rosser, Zoë ; Stoneking, Mark ; Jobling, Mark A. ; Sajantila, Antti ; Tyler-Smith, Chris 

    2004-01-01

    We have screened the nearly complete DNA sequence of the human Y chromosome for microsatellites (short tandem repeats) that meet the criteria of having a repeat-unit size of ⩾3 and a repeat count of ⩾8 and thus are likely to be easy to genotype accurately and to be polymorphic. Candidate loci were tested in silico for novelty and for probable Y specificity, and then they were tested experimentally to identify Y-specific loci and to assess their polymorphism. This yielded 166 useful new Y-chromosomal microsatellites, 139 of which were polymorphic, in a sample of eight diverse Y chromosomes representing eight Y-SNP haplogroups. This large sample of microsatellites, together with 28 previously known markers analyzed here—all sharing a common evolutionary history—allowed us to investigate the factors influencing their variation. For simple microsatellites, the average repeat count accounted for the highest proportion of repeat variance (∼34%). For complex microsatellites, the largest proportion of the variance (again, ∼34%) was explained by the average repeat count of the longest homogeneous array, which normally is variable. In these complex microsatellites, the additional repeats outside the longest homogeneous array significantly increased the variance, but this was lower than the variance of a simple microsatellite with the same total repeat count. As a result of this work, a large number of new, highly polymorphic Y-chromosomal microsatellites are now available for population-genetic, evolutionary, genealogical, and forensic investigations. PMID:15195656

  5. Comprehensive, Quantitative Risk Assessment of CO{sub 2} Geologic Sequestration

    SciTech Connect

    Lepinski, James

    2013-09-30

    A Quantitative Failure Modes and Effects Analysis (QFMEA) was developed to conduct comprehensive, quantitative risk assessments on CO{sub 2} capture, transportation, and sequestration or use in deep saline aquifers, enhanced oil recovery operations, or enhanced coal bed methane operations. The model identifies and characterizes potential risks; identifies the likely failure modes, causes, effects and methods of detection; lists possible risk prevention and risk mitigation steps; estimates potential damage recovery costs, mitigation costs and costs savings resulting from mitigation; and ranks (prioritizes) risks according to the probability of failure, the severity of failure, the difficulty of early failure detection and the potential for fatalities. The QFMEA model generates the necessary information needed for effective project risk management. Diverse project information can be integrated into a concise, common format that allows comprehensive, quantitative analysis, by a cross-functional team of experts, to determine: What can possibly go wrong? How much will damage recovery cost? How can it be prevented or mitigated? What is the cost savings or benefit of prevention or mitigation? Which risks should be given highest priority for resolution? The QFMEA model can be tailored to specific projects and is applicable to new projects as well as mature projects. The model can be revised and updated as new information comes available. It accepts input from multiple sources, such as literature searches, site characterization, field data, computer simulations, analogues, process influence diagrams, probability density functions, financial analysis models, cost factors, and heuristic best practices manuals, and converts the information into a standardized format in an Excel spreadsheet. Process influence diagrams, geologic models, financial models, cost factors and an insurance schedule were developed to support the QFMEA model. Comprehensive, quantitative risk assessments

  6. Comprehensive review on lactate metabolism in human health.

    PubMed

    Adeva-Andany, M; López-Ojén, M; Funcasta-Calderón, R; Ameneiros-Rodríguez, E; Donapetry-García, C; Vila-Altesor, M; Rodríguez-Seijas, J

    2014-07-01

    Metabolic pathways involved in lactate metabolism are important to understand the physiological response to exercise and the pathogenesis of prevalent diseases such as diabetes and cancer. Monocarboxylate transporters are being investigated as potential targets for diagnosis and therapy of these and other disorders. Glucose and alanine produce pyruvate which is reduced to lactate by lactate dehydrogenase in the cytoplasm without oxygen consumption. Lactate removal takes place via its oxidation to pyruvate by lactate dehydrogenase. Pyruvate may be either oxidized to carbon dioxide producing energy or transformed into glucose. Pyruvate oxidation requires oxygen supply and the cooperation of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. Congenital or acquired deficiency on gluconeogenesis or pyruvate oxidation, including tissue hypoxia, may induce lactate accumulation. Both obese individuals and patients with diabetes show elevated plasma lactate concentration compared to healthy subjects, but there is no conclusive evidence of hyperlactatemia causing insulin resistance. Available evidence suggests an association between defective mitochondrial oxidative capacity in the pancreatic β-cells and diminished insulin secretion that may trigger the development of diabetes in patients already affected with insulin resistance. Several mutations in the mitochondrial DNA are associated with diabetes mellitus, although the pathogenesis remains unsettled. Mitochondrial DNA mutations have been detected in a number of human cancers. d-lactate is a lactate enantiomer normally formed during glycolysis. Excess d-lactate is generated in diabetes, particularly during diabetic ketoacidosis. d-lactic acidosis is typically associated with small bowel resection. Copyright © 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  7. What experimental experience affects dogs' comprehension of human communicative actions?

    PubMed

    Hauser, Marc D; Comins, Jordan A; Pytka, Lisa M; Cahill, Donal P; Velez-Calderon, Sofia

    2011-01-01

    Studies of dogs report that individuals reliably respond to the goal-directed communicative actions (e.g., pointing) of human experimenters. All of these studies use some version of a multi-trial approach, thereby allowing for the possibility of rapid learning within an experimental session. The experiments reported here ask whether dogs can respond correctly to a communicative action based on only a single presentation, thereby eliminating the possibility of learning within the experimental context. We tested 173 dogs. For each dog reaching our test criteria, we used a single presentation of six different goal-directed actions within a session, asking whether they correctly follow to a target goal (container with concealed food) a (1) distal hand point, (2) step toward one container, (3) hand point to one container followed by step toward the other, (4) step toward one container and point to the other, (5) distal foot point with the experimenter's hands free, and (6) distal foot point with the experimenter's hands occupied. Given only a single presentation, dogs selected the correct container when the experimenter hand pointed, foot pointed with hands occupied, or stepped closer to the target container, but failed on the other actions, despite using the same method. The fact that dogs correctly followed foot pointing with hands occupied, but not hands free, suggests that they are sensitive to environmental constraints, and use this information to infer rational, goal-directed action. We discuss these results in light of the role of experience in recognizing communicative gestures, as well as the significance of coding criteria for studies of canine competence.

  8. Space Radiation and Risks to Human Health

    NASA Technical Reports Server (NTRS)

    Huff, Janice L.

    2014-01-01

    The radiation environment in space poses significant challenges to human health and is a major concern for long duration manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as x-rays and gamma-rays. Galactic cosmic rays consist of high energy and high mass nuclei as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. The major health issues of concern are the risks of radiation carcinogenesis, acute and late decrements to the central nervous system, degenerative tissue effects such as cardiovascular disease, as well as possible acute radiation syndromes due to an unshielded exposure to a large solar particle event. The NASA Human Research Program's Space Radiation Program Element is focused on characterization and mitigation of these space radiation health risks along with understanding these risks in context of the other biological stressors found in the space environment. In this overview, we will provide a description of these health risks and the Element's research strategies to understand and mitigate these risks.

  9. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters.

    PubMed

    Aagaard, Kjersti; Petrosino, Joseph; Keitel, Wendy; Watson, Mark; Katancik, James; Garcia, Nathalia; Patel, Shital; Cutting, Mary; Madden, Tessa; Hamilton, Holli; Harris, Emily; Gevers, Dirk; Simone, Gina; McInnes, Pamela; Versalovic, James

    2013-03-01

    The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.

  10. Comprehensive Analysis of 5-Aminolevulinic Acid Dehydrogenase (ALAD) Variants and Renal Cell Carcinoma Risk among Individuals Exposed to Lead

    PubMed Central

    van Bemmel, Dana M.; Boffetta, Paolo; Liao, Linda M.; Berndt, Sonja I.; Menashe, Idan; Yeager, Meredith; Chanock, Stephen; Karami, Sara; Zaridze, David; Matteev, Vsevolod; Janout, Vladimir; Kollarova, Hellena; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonilia; Mates, Dana; Slamova, Alena; Rothman, Nathaniel; Han, Summer S.; Rosenberg, Philip S.; Brennan, Paul; Chow, Wong-Ho; Moore, Lee E.

    2011-01-01

    Background Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD) gene affects lead toxicokinetics and may modify the adverse effects of lead. Methods The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs) tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC). Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Results The adjusted risk associated with the ALAD variant rs8177796CT/TT was increased (OR = 1.35, 95%CI = 1.05–1.73, p-value = 0.02) when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles (GGOR = 2.68, 95%CI = 1.17–6.12, p = 0.01; GAOR = 1.79, 95%CI = 1.06–3.04 with an interaction approaching significance (pint = 0.06).. No significant modification in RCC risk was observed for the functional variant rs1800435(K68N). Haplotype analysis identified a region associated with risk supporting tagging SNP results. Conclusion A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure. PMID:21799727

  11. Comprehensive evaluation of medical conditions associated with risk of non-Hodgkin lymphoma using Medicare claims (“MedWAS”)

    PubMed Central

    Engels, Eric A.; Parsons, Ruth; Besson, Caroline; Morton, Lindsay M.; Enewold, Lindsey; Ricker, Winnie; Yanik, Elizabeth L.; Arem, Hannah; Austin, April A.; Pfeiffer, Ruth M.

    2016-01-01

    Background Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method (“medical condition-wide association study,” MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. Methods Using SEER-Medicare data, we conducted a case-control study comparing NHL cases (N=52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL], diffuse large B-cell lymphoma [DLBCL], follicular lymphoma, marginal zone lymphoma [MZL], T-cell lymphoma [TCL]) to controls (N=200,000).We systematically screened for associations with 5926 medical conditions documented in Medicare claims more than one year before selection. Results Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (odds ratios [ORs] 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of non-melanoma skin cancer (ORs 1.19–1.55), actinic keratosis (1.12–1.25), or hemolytic anemia (1.64–4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20–4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). Conclusion Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. Impact These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. PMID:27197296

  12. Comprehensive Evaluation of Medical Conditions Associated with Risk of Non-Hodgkin Lymphoma using Medicare Claims ("MedWAS").

    PubMed

    Engels, Eric A; Parsons, Ruth; Besson, Caroline; Morton, Lindsay M; Enewold, Lindsey; Ricker, Winnie; Yanik, Elizabeth L; Arem, Hannah; Austin, April A; Pfeiffer, Ruth M

    2016-07-01

    Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method ("medical condition-wide association study," MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case-control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection. Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19-1.55), actinic keratosis (1.12-1.25), or hemolytic anemia (1.64-4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20-4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105-13. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. Dynamic risk control by human nucleus accumbens

    PubMed Central

    Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio

    2015-01-01

    Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

  14. Dynamic risk control by human nucleus accumbens.

    PubMed

    Nachev, Parashkev; Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio; Strange, Bryan

    2015-12-01

    Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established.

  15. Building a Community of Learning: A Comprehensive Approach to Assisting At-Risk Students. AIR 1997 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Walleri, R. Dan; Stoker, Cheryl L.; Stoering, Juliette

    This case study of a student retention program for at-risk students at Mount Hood Community College (Oregon) contends that student retention programs are seldom as holistic and comprehensive as intended. The study analyzed three areas: the design and implementation of a comprehensive program to improve student retention; the organizational…

  16. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

    PubMed

    O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2015-10-01

    Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.

  17. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

    PubMed Central

    O’Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica MJ; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2015-01-01

    Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3,633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6,607 EC cases and 37,925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P = 1.86 × 10−5), which was stronger for cancers of endometrioid subtype (P = 3.76 × 10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482

  18. HIV and sexual risk behaviors among recognized high-risk groups in Bangladesh: need for a comprehensive prevention program.

    PubMed

    Islam, Md Mofizul; Conigrave, Katherine M

    2008-07-01

    To examine trends in HIV and related risk behaviors among recognized high-risk groups in Bangladesh, the types and extent of prevention initiatives that have been undertaken, and highlight the immediate needs. Journal publications and conference abstracts and proceedings were reviewed. Experts involved in the development and evaluation of current programs or policy were contacted for official reports and policy documents. The trends in sexual risk behaviors over five rounds of national surveillance were tabulated. Gaps in the ongoing prevention interventions have been assessed in the light of the Anderson-May equation. Periodic surveillance on recognized high-risk groups shows that HIV prevalence has been increasing steadily. In the capital city, HIV prevalence in one subset of a high-risk group is close to the level of a concentrated epidemic (4.9%). The high prevalence of sexual risk behaviors among drug users and sex workers and their clients is alarming. Although a small increase in condom use and a reduction of syphilis have been noted among subsets of high-risk groups in recent years, this is clearly not enough to curb the threat of a possible HIV epidemic. There is an urgent need for a comprehensive prevention program that should include more efforts on education and condom promotion, effective management of all sexually transmitted infections, a screening program for migrant workers, the continuation of both behavioral and serological components of HIV surveillance, and the expansion of surveillance to cover the remaining high-risk groups, with due consideration to the consistency of surveillance indicators.

  19. Comprehensive transportation risk assessment system based on unit-consequence factors

    SciTech Connect

    Biwer, B.M.; Monette, F.A.; LePoire, D.J.; Chen, S.Y.

    1994-02-01

    The U.S. Department of Energy (DOE) Environmental Restoration and Waste Management Programmatic Environmental Impact Statement requires a comprehensive transportation risk analysis of radioactive waste shipments for large shipping campaigns. Thousands of unique shipments involving truck and rail transport must be analyzed; a comprehensive risk analysis is impossible with currently available methods. Argonne National Laboratory developed a modular transportation model that can handle the demands imposed by such an analysis. The modular design of the model facilitates the simple addition/updating of transportation routes and waste inventories, as required, and reduces the overhead associated with file maintenance and quality assurance. The model incorporates unit-consequences factors generated with the RADTRAN 4 transportation risk analysis code that are combined with an easy-to-use, menu-driven interface on IBM-compatible computers running under DOS. User selection of multiple origin/destination site pairs for the shipment of multiple radioactive waste inventories is permitted from pop-up lists. Over 800 predefined routes are available among more than 30 DOE sites and waste inventories that include high-level waste, spent nuclear fuel, transuranic waste, low-level waste, low-level mixed waste, and greater-than-Class C waste.

  20. Identification of Comprehensive Geriatric Assessment Based Risk Factors for Malnutrition in Elderly Asian Cancer Patients

    PubMed Central

    Ong, Whee Sze; Rajasekaran, Tanujaa; Nee Koo, Khai; Chan, Li Li; Poon, Donald; Roy Chowdhury, Anupama; Krishna, Lalit; Kanesvaran, Ravindran

    2016-01-01

    Purpose Elderly cancer patients are at increased risk for malnutrition. We aim to identify comprehensive geriatric assessment (CGA) based clinical factors associated with increased nutritional risk and develop a clinical scoring system to identify nutritional risk in elderly cancer patients. Patients and Methods CGA data was collected from 249 Asian patients aged 70 years or older. Nutritional risk was assessed based on the Nutrition Screening Initiative (NSI) checklist. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test. Discrimination ability was assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping. Results Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3–4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14–5.69), ECOG performance status of 2–4 (OR 3.04; 95% CI, 1.57–5.88), presence of depression (OR 5.99; 95% CI, 1.99–18.02) and haemoglobin levels <12 g/dL (OR 3.00; 95% CI 1.54–5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test’s p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation. Conclusion Having advanced stage of cancer, poor performance status, depression and anaemia were found to be predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions that may improve treatment tolerance, quality of life and survival outcomes. PMID:27231951

  1. New approaches in human health risk assessment

    PubMed Central

    Abass, Khaled; Carlsen, Anders; Rautio, Arja

    2016-01-01

    Studies on the precise impact of environmental pollutants on human health are difficult to undertake and interpret, because many genetic and environmental factors influence health at the same time and to varying degrees. Our chapter in the AMAP report was based on new approaches to describe risks and future needs. In this paper, we will introduce the issues associated with risk assessment of single chemicals, and present suggestions for future studies as well as a summary of lessons learned during the health-related parts of the European Union-funded FP7 project ArcRisk (Arctic Health Risks: Impacts on health in the Arctic and Europe owing to climate-induced changes in contaminant cycling, 2009–2014; www.arcrisk.eu). PMID:27974141

  2. Human milk pasteurization: benefits and risks.

    PubMed

    O'Connor, Deborah L; Ewaschuk, Julia B; Unger, Sharon

    2015-05-01

    Recent findings substantiate that the optimal method of nourishing preterm, very low birth weight infants (VLBW, born <1500 g) is through appropriately nutrient-enriched human milk, which is frequently provided as pasteurized donor milk. The availability of donor milk for VLBW infants during initial hospitalization continues to increase with the launch of new milk banks in North America. The majority of North American neonatal ICUs now have written policies governing the provision of donor milk. The purpose of this review is to summarize recent evidence regarding the risks and benefits of pasteurization of human milk and outcomes associated with its provision to VLBW preterm infants. Studies investigating the impact of collection, storage and pasteurization on the bacteriostatic, immunologic and nutritional aspects of human milk continue to be published, generally revealing a partial, but not complete reduction in bioactivity. Risk of contamination of pasteurized donor human milk with pathogenic agents is mitigated through pasteurization. New pasteurization methods aiming to maintain the safety of pooled human milk while better preserving bioactivity are under investigation. Provision of a human milk-derived diet to preterm VLBW infants is associated with improved outcomes.

  3. A phased approach to planning a comprehensive risk communication program for a RCRA facility investigation

    SciTech Connect

    Walker, L.B.; Dombrowski, F.; Sheehan, P. |

    1994-12-31

    The purpose of preparing a risk communication plan for a facility conducting human health and ecological risk assessments is to provide a framework for communicating risks to three main groups: the company and facility staff, involved regulatory and trustee agencies, and interested public groups. Interested public groups are varied, and may include environmental and economic organizations, recreational clubs, and property owners. Within this framework, the risk communication plan should be carefully defined by regulatory requirements for public disclosure, public involvement, and any goals the facility may wish to achieve above and beyond the regulatory mandate (e.g., public relations). A phased approach to a risk communication plan is presented which outlines the following steps: (1) investigate, listen to and understand the concerns of the interested groups as they relate to the risk assessment, (2) educate interested groups on risk assessment terminology and methods so that they can better interpret risk assessment results, and (3) present risk assessments in an understandable and consistent manner that addresses specific group concerns. Recommendations are given for conducting background investigations, initiating interactions, and selecting risk education and presentation forums for the various interested groups.

  4. Infectious risk moments: a novel, human factors-informed approach to infection prevention.

    PubMed

    Clack, Lauren; Schmutz, Jan; Manser, Tanja; Sax, Hugo

    2014-08-01

    We pilot tested a novel human factors-informed concept to identify infectious risk moments (IRMs) that occur with high frequency during routine intensive care. Following 30 observation-hours, 28 potential IRMs related to hand hygiene, gloves, and objects were expert rated. A comprehensive IRM inventory may provide valuable taxonomy for research, training, and intervention.

  5. Sudden cardiac death in hemodialysis patients: a comprehensive care approach to reduce risk.

    PubMed

    Pun, Patrick H; Middleton, John P

    2012-01-01

    Sudden cardiac death is a major problem in hemodialysis patients, and our understanding of this disease is underdeveloped. The lack of a precise definition tailored for use in the hemodialysis population limits the reliability of epidemiologic reports. Efforts should be directed toward an accurate classification of all deaths that occur in this vulnerable population. The traditional paradigm of disease pathophysiology based on known cardiac risk factors appears to be inadequate to explain the magnitude of sudden cardiac death risk in chronic kidney disease, and numerous unique cofactors and exposures appear to determine risk in this population. Well-designed cohort studies will be needed for a basic understanding of disease pathophysiology and risk factors, and randomized intervention trials will be needed before best management practices can be implemented. This review examines available data to describe the characteristics of the high-risk patient and suggests a comprehensive common sense approach to prevention using existing cardiovascular medications and reducing and monitoring potential dialysis-related arrhythmic triggers. Other unproven cardiovascular therapies such as implantable cardioverter defibrillators should be used on a case-by-case basis, with recognition of the associated hazards that these devices carry among hemodialysis patients.

  6. Comprehensive cardiovascular risk management--what does it mean in practice?

    PubMed

    Erhardt, Leif; Moller, Robert; Puig, Juan García

    2007-01-01

    The continued movement away from the treatment of individual cardiovascular (CV) risk factors to managing overall and lifetime CV risk is likely to have a significant impact on slowing the rate of increase in cardiovascular disease (CVD). However, the management of CVD is currently far from optimal even in parts of the world with well-developed and well-funded healthcare systems. Effective implementation of the knowledge, treatment guidelines, diagnostic tools, therapeutic interventions, and management programs that exist for CVD continues to evade us. A thorough understanding of the multifactorial nature of CVD is essential to its effective management. Improvements continue to be made to management guidelines, risk assessment tools, treatments, and care programs pertaining to CVD. Ultimately, however, preventing the epidemic of CVD will require a combination of both medical and public health approaches. In addition to improvements in the "high-risk" strategy, which forms the basis of current CVD management, an increase in the utilization of population-based management strategies needs to be made to attempt to reduce the number of patients falling within the "at-risk" stratum for CVD. This review outlines how a comprehensive approach to CVD management might be achieved.

  7. Topical Review: A Comprehensive Risk Model for Disordered Eating in Youth With Type 1 Diabetes

    PubMed Central

    Fischer, Sarah; Young-Hyman, Deborah

    2015-01-01

    Objectives Provide an updated literature review on prevalence, measurement, and correlates of disordered eating in youth with Type 1 diabetes (T1D), present a novel theoretical risk model (i.e., The Modified Dual Pathway Model) for disordered eating in youth with T1D incorporating psychosocial and physiological risk factors, and discuss clinical implications. Methods Literature review of prevalence, correlates, risk factors, and outcomes of disordered eating behavior (DEB) in youth with T1D. Results Insulin treatment, subsequent weight gain, and disruptions to hunger and satiety regulation are hypothesized disease-related mechanisms through which the treatment of T1D may increase vulnerability to development of behavior characterized as DEB. The Modified Dual Pathway Model integrates these factors with a validated psychosocial risk (body dissatisfaction, depression, and abstinence violation) model for DEB in nondiabetic youth. Conclusions The Modified Dual Pathway model of DEB in youth with T1D is a comprehensive representation of both psychosocial and T1D-related risk factors with the potential to inform future interventions for this population. PMID:25502449

  8. Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres

    PubMed Central

    Pressoir, M; Desné, S; Berchery, D; Rossignol, G; Poiree, B; Meslier, M; Traversier, S; Vittot, M; Simon, M; Gekiere, J P; Meuric, J; Serot, F; Falewee, M N; Rodrigues, I; Senesse, P; Vasson, M P; Chelle, F; Maget, B; Antoun, S; Bachmann, P

    2010-01-01

    Background: This epidemiological observational study aimed at determining the prevalence of malnutrition in non-selected adults with cancer, to identify risk factors of malnutrition and correlate the results with length of stay and 2-month mortality. Methods: This prospective multicentre 1-day study conducted in 17 French Comprehensive Cancer Centres included 1545 patients. Body mass index (BMI), weight loss (WL) in the past 6 months and age were routinely recorded according to the French national recommendations for hospitalised patients; malnutrition was rated as absent, moderate or severe according to the level of WL and BMI. Age, sex, tumour site, type of hospitalisation and treatment, disease stage, World Health Organisation performance status (PS) and antibiotic therapy were the potential malnutrition risk factors tested. Follow-up at 2 months allowed to determine the correlation with length of stay and mortality. Results: Malnutrition was reported in 30.9% of patients, and was rated as severe in 12.2%. In multivariate analysis, only pre-existing obesity (BMI⩾30), PS ⩾2 and head-and-neck or upper digestive cancers were associated with increased risk of malnutrition. Antibiotics use was significantly higher in malnourished patients (35.5 vs 22.8% P<0.001). Severe malnutrition was independently associated with mortality. The median length of stay was 19.3±19.4 days for malnourished patients vs 13.3±19.4 days for others (P<0.0001). Conclusion: In French Comprehensive Cancer Centres, one out of three cancer patients are malnourished and this was associated with a longer length of stay. Pre-existing obesity could be identified as a new risk factor for malnutrition in our cancer patient population perhaps because of a misidentification or a delay in nutrition support in this category of patients. PMID:20160725

  9. Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.

    PubMed

    Pressoir, M; Desné, S; Berchery, D; Rossignol, G; Poiree, B; Meslier, M; Traversier, S; Vittot, M; Simon, M; Gekiere, J P; Meuric, J; Serot, F; Falewee, M N; Rodrigues, I; Senesse, P; Vasson, M P; Chelle, F; Maget, B; Antoun, S; Bachmann, P

    2010-03-16

    This epidemiological observational study aimed at determining the prevalence of malnutrition in non-selected adults with cancer, to identify risk factors of malnutrition and correlate the results with length of stay and 2-month mortality. This prospective multicentre 1-day study conducted in 17 French Comprehensive Cancer Centres included 1545 patients. Body mass index (BMI), weight loss (WL) in the past 6 months and age were routinely recorded according to the French national recommendations for hospitalised patients; malnutrition was rated as absent, moderate or severe according to the level of WL and BMI. Age, sex, tumour site, type of hospitalisation and treatment, disease stage, World Health Organisation performance status (PS) and antibiotic therapy were the potential malnutrition risk factors tested. Follow-up at 2 months allowed to determine the correlation with length of stay and mortality. Malnutrition was reported in 30.9% of patients, and was rated as severe in 12.2%. In multivariate analysis, only pre-existing obesity (BMI> or =30), PS > or =2 and head-and-neck or upper digestive cancers were associated with increased risk of malnutrition. Antibiotics use was significantly higher in malnourished patients (35.5 vs 22.8%; P<0.001). Severe malnutrition was independently associated with mortality. The median length of stay was 19.3+/-19.4 days for malnourished patients vs 13.3+/-19.4 days for others (P<0.0001). In French Comprehensive Cancer Centres, one out of three cancer patients are malnourished and this was associated with a longer length of stay. Pre-existing obesity could be identified as a new risk factor for malnutrition in our cancer patient population perhaps because of a misidentification or a delay in nutrition support in this category of patients.

  10. An Evidence Base for Human Spaceflight Risks in Wikipedia

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig; Steil, Jennifer; Lumpkins, Sarah; Pellis, Neal

    2013-01-01

    NASA's Human Research Program (HRP) is focused on understanding and mitigating thirty two risks to crew health and performance in exploration missions beyond low Earth orbit. The HRP has developed an evidence report for each of the risks. Most evidence reports are a brief review article describing the evidence related to a specified risk, written at a level appropriate for the scientifically educated, non-specialist reader. Each evidence report captured the current state of knowledge from both research and operations. Two limitations of the evidence reports have become apparent: 1) they are updated infrequently and 2) they do not take full advantage of the expertise available in other space agencies and in related fields of terrestrial research. Therefore, the HRP is experimenting with the use of Wikipedia articles as a repository for evidence. Wikipedia's accessibility to the international space flight community and researchers in related terrestrial fields creates the opportunity to generate a more timely and comprehensive evidence base. Initial Wikipedia articles were populated for seven risks using a subset of the information in the HRP-approved evidence reports: Fatigue and Sleep Loss, Treating An Ill or Injured Crew Member, Radiation Carcinogenesis, Visual Impairment and Intracranial Pressure, Renal Stone Formation, Team Cohesion, and Intervertebral Disc Damage. Since the initial articles were created, there have been additions to these Wikipedia articles, including content from sources outside the HRP, and editorial changes to the pages. We will report on the nature of the contributions made after the initial articles were created, the comprehensiveness of the resulting Wikipedia articles, and the effort required to maintain quality control of the content. The Wikipedia approach will also be compared to wiki efforts that exert more traditional editorial control of content prior to posting.

  11. Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation.

    PubMed

    Ozsolak, Fatih; Kapranov, Philipp; Foissac, Sylvain; Kim, Sang Woo; Fishilevich, Elane; Monaghan, A Paula; John, Bino; Milos, Patrice M

    2010-12-10

    The emerging discoveries on the link between polyadenylation and disease states underline the need to fully characterize genome-wide polyadenylation states. Here, we report comprehensive maps of global polyadenylation events in human and yeast generated using refinements to the Direct RNA Sequencing technology. This direct approach provides a quantitative view of genome-wide polyadenylation states in a strand-specific manner and requires only attomole RNA quantities. The polyadenylation profiles revealed an abundance of unannotated polyadenylation sites, alternative polyadenylation patterns, and regulatory element-associated poly(A)(+) RNAs. We observed differences in sequence composition surrounding canonical and noncanonical human polyadenylation sites, suggesting novel noncoding RNA-specific polyadenylation mechanisms in humans. Furthermore, we observed the correlation level between sense and antisense transcripts to depend on gene expression levels, supporting the view that overlapping transcription from opposite strands may play a regulatory role. Our data provide a comprehensive view of the polyadenylation state and overlapping transcription.

  12. Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

    PubMed

    Gibson, Todd M; Brennan, Paul; Han, Summer; Karami, Sara; Zaridze, David; Janout, Vladimir; Kollarova, Helen; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Slamova, Alena; Pfeiffer, Ruth M; Stolzenberg-Solomon, Rachael Z; Mayne, Susan T; Yeager, Meredith; Chanock, Stephen; Rothman, Nat; Chow, Wong-Ho; Rosenberg, Philip S; Boffetta, Paolo; Moore, Lee E

    2011-01-01

    Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.

  13. Comprehensive Evaluation of One-Carbon Metabolism Pathway Gene Variants and Renal Cell Cancer Risk

    PubMed Central

    Gibson, Todd M.; Brennan, Paul; Han, Summer; Karami, Sara; Zaridze, David; Janout, Vladimir; Kollarova, Helen; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Slamova, Alena; Pfeiffer, Ruth M.; Stolzenberg-Solomon, Rachael Z.; Mayne, Susan T.; Yeager, Meredith; Chanock, Stephen; Rothman, Nat; Chow, Wong-Ho; Rosenberg, Philip S.; Boffetta, Paolo; Moore, Lee E.

    2011-01-01

    Introduction Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. Methods Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. Results The strongest associations with RCC risk were observed for SLC19A1 (Pmin-P = 0.03) and MTHFR (Pmin-P = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. Conclusions To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings. PMID:22039442

  14. Human Plague Risk: Spatial-Temporal Models

    NASA Technical Reports Server (NTRS)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  15. Comprehensive analysis of an ecological risk assessment of the Daliao River estuary, China.

    PubMed

    Yu, Ge; Chen, Jing; Zhang, Xueqing; Li, Zhengyan

    2013-08-01

    At present, most estuarine ecological risk studies are based on terrestrial ecosystem models, which ignore spatial heterogeneity. The Daliao River estuary has representative characteristics of many estuaries in China, and we used this estuary as the study area to formulate an estuarine ecological risk evaluation model. Targeting the estuary's special hydrodynamic condition, this model incorporated variables that were under the influence of human activities and used them as the major factors for partitioning sections of the river according to risk values. It also explored the spatial and temporal distribution laws of estuarine ecological risk. The results showed that, on the whole, the ecological risk of the Daliao River estuary area was relatively high. At a temporal level, runoff was the main factor resulting in differences in ecological risk, while at the spatial level, the ecological risk index was affected by pollutants carried by runoff from upstream, as well as downstream pollution emissions and dilution by seawater at the mouth of the sea. The characteristics of this model make it possible to simulate the spatial and temporal risk distribution in different regions and under different rainfall regimes. This model can thus be applied in other estuarine areas and provides some technical support for analysis and control of ecological destruction in estuary areas.

  16. Additional Treatments for High-Risk Obstetric Antiphospholipid Syndrome: a Comprehensive Review.

    PubMed

    Ruffatti, Amelia; Hoxha, Ariela; Favaro, Maria; Tonello, Marta; Colpo, Anna; Cucchini, Umberto; Banzato, Alessandra; Pengo, Vittorio

    2016-06-25

    Most investigators currently advocate prophylactic-dose heparin plus low-dose aspirin as the preferred treatment of otherwise healthy women with obstetric antiphospholipid syndrome, whilst women with a history of vascular thrombosis alone or associated with pregnancy morbidity are usually treated with therapeutic heparin doses in association with low-dose aspirin in an attempt to prevent both thrombosis and pregnancy morbidity. However, the protocols outlined above fail in about 20 % of pregnant women with antiphospholipid syndrome. Identifying risk factors associated with pregnancy failure when conventional therapies are utilized is an important step in establishing guidelines to manage these high-risk patients. Some clinical and laboratory risk factors have been found to be related to maternal-foetal complications in pregnant women on conventional therapy. However, the most efficacious treatments to administer to high-risk antiphospholipid syndrome women in addition to conventional therapy in order to avoid pregnancy complications are as yet unestablished. This is a comprehensive review on this topic and an invitation to participate in a multicentre study in order to identify the best additional treatments to be used in this subset of antiphospholipid syndrome patients.

  17. Risk of incident ESRD: a comprehensive look at cardiovascular risk factors and 17 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Bash, Lori D; Astor, Brad C; Coresh, Josef

    2010-01-01

    Diabetes and hypertension are potent risk factors for end-stage renal disease (ESRD). Previous studies suggest that other cardiovascular risk factors also may increase the risk of ESRD; however, risk associated with a comprehensive cardiovascular risk-factor assessment has not been quantified in a population-based sample. The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. 15,324 white and African American participants aged 45-64 years from 4 US communities were followed up after a baseline visit that occurred in 1987-1989. A comprehensive collection of cardiovascular risk factors were examined. Incidence of ESRD (transplant, dialysis, catheter placement or kidney failure, and death) exclusive of acute kidney failure was ascertained through active surveillance of hospitalizations through 2004. During a median 16-year follow-up, 241 cases of ESRD developed (incidence rate, 1.04 cases/1,000 person-years). Male sex, African American race, diabetes, hypertension, history of coronary heart disease, smoking, older age, body mass index, and triglyceride concentration were associated with increased risk of ESRD after adjustment for baseline estimated glomerular filtration rate (eGFR) and each other. There was a graded curvilinear association between risk of ESRD and lower baseline eGFR at levels < 90 mL/min/1.73 m(2) and moderately increased levels > 120 mL/min/1.73 m(2). The relative risk of eGFR on ESRD risk generally was greater in women and individuals with diabetes than in their counterparts. Only events occurring in acute-care hospitals were investigated (but there was long-term continuous active surveillance of events). We quantify the relative risk of ESRD in a community-based African American and white population associated with established cardiovascular risk factors (diabetes, hypertension, male sex, and African American race) and report prospective data identifying greater risk of ESRD associated with other cardiovascular

  18. Human bites and the risk of human immunodeficiency virus transmission.

    PubMed

    Pretty, I A; Anderson, G S; Sweet, D J

    1999-09-01

    The risk of human immunodeficiency virus (HIV) transmission following a bite injury is important to many groups of people. The first are those who are likely to be bitten as an occupational risk, such as police officers and institutional staff. Another group are represented by the victims and perpetrators of crimes involving biting, both in attack and defense situations. The possibility of these bites transmitting a potentially fatal disease is of interest to the physicians who treat such patients and the legal system which may have to deal with the repercussions of such a transmission. Bite injuries represent 1% of all emergency department admissions in the United States, and human bites are the third most common following those of dogs and cats. The worldwide epidemic of HIV and acquired immunodeficiency syndrome (AIDS) continues, with >5 million new cases last year and affecting 1 in 100 sexually active adults. A review of the literature concerning human bites, HIV and AIDS, HIV in saliva, and case examples was performed to examine the current opinion regarding the transmission of HIV via this route. A bite from an HIV-seropositive individual that breaks the skin or is associated with a previous injury carries a risk of infection for the bitten individual.

  19. The Improvement of Reading Comprehension of the Second Grade At-Risk Students Using Multisensory Methods of Instruction.

    ERIC Educational Resources Information Center

    Hunt, Geraldine

    A program was designed to improve the reading skills of the second grade at-risk students in a suburban K-6 elementary school located northwest of Chicago, Illinois. The second grade at-risk students could not read fluently at the conclusion of the academic school year, and consequently did not exhibit strong reading comprehension skills. A…

  20. A comprehensive transcript index of the human genome generated using microarrays and computational approaches

    PubMed Central

    Schadt, Eric E; Edwards, Stephen W; GuhaThakurta, Debraj; Holder, Dan; Ying, Lisa; Svetnik, Vladimir; Leonardson, Amy; Hart, Kyle W; Russell, Archie; Li, Guoya; Cavet, Guy; Castle, John; McDonagh, Paul; Kan, Zhengyan; Chen, Ronghua; Kasarskis, Andrew; Margarint, Mihai; Caceres, Ramon M; Johnson, Jason M; Armour, Christopher D; Garrett-Engele, Philip W; Tsinoremas, Nicholas F; Shoemaker, Daniel D

    2004-01-01

    Background Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22. Results The combination of microarray data with extensive genome annotations resulted in a set of 28,456 experimentally supported transcripts. This set of high-confidence transcripts represents the first experimentally driven annotation of the human genome. In addition, the results from genomic tiling suggest that a large amount of transcription exists outside of annotated regions of the genome and serves as an example of how this activity could be measured on a genome-wide scale. Conclusions These data represent one of the most comprehensive assessments of transcriptional activity in the human genome and provide an atlas of human gene expression over a unique set of gene predictions. Before the annotation of the human genome is considered complete, however, the previously unannotated transcriptional activity throughout the genome must be fully characterized. PMID:15461792

  1. The Human Genome Initiative: Implications for the Comprehensive School Health Program.

    ERIC Educational Resources Information Center

    James, Delores C. S.

    1994-01-01

    The Human Genome Initiative (HGI) constructs common resources for studying human genetics. Early identification of people at risk for genetic disorders allows for early education and counseling. HGI research will create inexpensive, reliable genetic tests and diagnoses to help teachers and school staff assess, compare, and channel students. (SM)

  2. The Human Genome Initiative: Implications for the Comprehensive School Health Program.

    ERIC Educational Resources Information Center

    James, Delores C. S.

    1994-01-01

    The Human Genome Initiative (HGI) constructs common resources for studying human genetics. Early identification of people at risk for genetic disorders allows for early education and counseling. HGI research will create inexpensive, reliable genetic tests and diagnoses to help teachers and school staff assess, compare, and channel students. (SM)

  3. Replacement of HEPA Filters at the LANL CMR Facility: Risks Reduced by Comprehensive Waste Characterization

    SciTech Connect

    Corpion, J.; Barr, A.; Martinez, P.; Bader, M.

    2002-02-28

    In March 2001, the Los Alamos National Laboratory (LANL) completed the replacement of 720 radioactively contaminated HEPA filters for $5.7M. This project was completed five months ahead of schedule and $6.0M under budget with no worker injuries or contaminations. Numerous health and safety, environmental, and waste disposal problems were overcome, including having to perform work in a radioactively contaminated work environment, that was also contaminated with perchlorates (potential explosive). High waste disposal costs were also an issue. A project risk analysis and government cost estimate determined that the cost of performing the work would be $11.8M. To reduce risk, a $1.2M comprehensive condition assessment was performed to determine the degree of toxic and radioactive contamination trapped on the HEPA filters; and to determine whether explosive concentrations of perchlorates were present. Workers from LANL and personnel from Waldheim International of Knoxville, TN collected hundreds of samples wearing personnel protective gear against radioactive, toxic, and explosive hazards. LANL also funded research at the New Mexico Institute of Mining and Technology to determine the explosivity of perchlorates. The data acquired from the condition assessment showed that toxic metals, toxic organic compounds, and explosive concentrations of perchlorates were absent. The data also showed that the extent of actinide metal contamination was less than expected, reducing the potential of transuranic waste generation by 50%. Consequently, $4.2M in cost savings and $1.8M in risk reduction were realized by increased worker productivity and waste segregation.

  4. Replacement of HEPA Filters at the LANL CMR Facility : risk reduced by comprehensive waste characterization

    SciTech Connect

    Corpion, J. C.

    2002-01-01

    In March 2001, the Los Alamos National Laboratory (LANL) completed the replacement of 720 radioactively contaminated HEPA filters for $5.7M. This project was completed five months ahead of schedule and $6.0M under budget with no worker injuries or contaminations. Numerous health and safety, environmental, and waste disposal problems were overcome, including having to perform work in a radioactively contaminated work environment, that was also contaminated with perchlorates (potential explosive). High waste disposal costs were also an issue. A project risk analysis and government cost estimate determined that the cost of performing the work would be $11.8M. To reduce risk, a $1.2M comprehensive condition assessment was performed to determine the degree of toxic and radioactive contamination trapped on the HEPA filters; and to determine whether explosive concentrations of perchlorates were present. Workers from LANL and personnel from Waldheim International of Knoxville, TN collected hundreds of samples wearing personnel protective gear against radioactive, toxic, and explosive hazards. LANL also funded research at the New Mexico Institute of Mining and Technology to determine the explosivity of perchlorates. The data acquired from the condition assessment showed that toxic metals, toxic organic compounds, and explosive concentrations of perchlorates were absent. The data also showed that the extent of actinide metal contamination was less than expected, reducing the potential of transuranic waste generation by 50%. Consequently, $4.2M in cost savings and $1.8M in risk reduction were realized by increased worker productivity and waste segregation.

  5. Fukushima nuclear power plant accident and comprehensive health risk management-global radiocontamination and information disaster.

    PubMed

    Yamashita, Shunichi

    2014-06-01

    The Great East Japan Earthquake on March 11, 2011, besides further studying the appropriateness of the initial response and post-countermeasures against the severe Fukushima nuclear accident, has now increased the importance of the epidemiological study in comprehensive health risk management and radiation protection; lessons learnt from the Chernobyl accident should be also implemented. Therefore, since May 2011, Fukushima Prefecture has started the "Fukushima Health Management Survey Project" for the purpose of long-term health care administration and early diagnosis/treatment for the prefectural residents. Basic survey is under investigation on a retrospective estimation of external exposure of the first four months. As one of the four detailed surveys, the thyroid ultrasound examination has clarified the increased detection rate of childhood thyroid cancers as a screening effect in the past three years and so thyroid cancer occurrence by Fukushima nuclear power plant accident, especially due to radioactive iodine will be discussed despite of difficult challenge of accurate estimation of low dose and low-dose rate radiation exposures. Through the on-site valuable experience and a difficult challenge for recovery, we should learn the lessons from this severe and large-scale nuclear accident, especially how to countermeasure against public health emergency at the standpoint of health risk and also social risk management.

  6. Erosion investigation and sediment quality measurements for a comprehensive risk assessment of contaminated aquatic sediments.

    PubMed

    Haag, I; Kern, U; Westrich, B

    2001-02-05

    In this paper, an assessment strategy is introduced which allows one to evaluate the ecological hazard of contaminated sediments in connection with the risk of in-stream erosion. Special techniques for sediment sampling, non-intrusive density profiling, and depth related measurement of erosion are presented, which, in combination with ecological aspects, lead to a comprehensive risk assessment of fluvial sediments. The strategy was applied to a lock-regulated reach of the River Neckar in Germany. The spatial pattern of contamination in the river reservoir was found to be remarkably heterogeneous. At some sites, very high heavy metal concentrations were detected at the sediment surface. A sudden increase in contamination with depth at other sites could be attributed to an erosional unconformity. The critical shear stress of erosion for old contaminated sediments is higher than for recently deposited material. Nevertheless, during major flood events, bottom shear stress in the river exceeds the critical shear stresses of erosion of all sediments. Accordingly, there is a substantial risk that old contaminated sediment can be mobilised from the reservoir and transported downstream.

  7. Fukushima Nuclear Power Plant Accident and Comprehensive Health Risk Management—Global Radiocontamination and Information Disaster

    PubMed Central

    2014-01-01

    The Great East Japan Earthquake on March 11, 2011, besides further studying the appropriateness of the initial response and post-countermeasures against the severe Fukushima nuclear accident, has now increased the importance of the epidemiological study in comprehensive health risk management and radiation protection; lessons learnt from the Chernobyl accident should be also implemented. Therefore, since May 2011, Fukushima Prefecture has started the “Fukushima Health Management Survey Project” for the purpose of long-term health care administration and early diagnosis/treatment for the prefectural residents. Basic survey is under investigation on a retrospective estimation of external exposure of the first four months. As one of the four detailed surveys, the thyroid ultrasound examination has clarified the increased detection rate of childhood thyroid cancers as a screening effect in the past three years and so thyroid cancer occurrence by Fukushima nuclear power plant accident, especially due to radioactive iodine will be discussed despite of difficult challenge of accurate estimation of low dose and low-dose rate radiation exposures. Through the on-site valuable experience and a difficult challenge for recovery, we should learn the lessons from this severe and large-scale nuclear accident, especially how to countermeasure against public health emergency at the standpoint of health risk and also social risk management. PMID:25425958

  8. Comprehensive Cardiovascular Risk Reduction and Cardiac Rehabilitation in Diabetes and the Metabolic Syndrome

    PubMed Central

    Heinl, Robert E.; Dhindsa, Devinder S.; Mahlof, Elliot N.; Schultz, William M.; Ricketts, Johnathan C.; Varghese, Tina; Esmaeeli, Amirhossein; Allard-Ratick, Marc P.; Millard, Anthony J.; Kelli, Heval M.; Sandesara, Pratik B.; Eapen, Danny J.; Sperling, Laurence

    2017-01-01

    The epidemic of obesity has contributed to a growing burden of metabolic syndrome (MetS) and diabetes mellitus (DM) worldwide. MetS is defined as central obesity along with associated factors such as hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, and hypertension. MetS and DM are associated with significant cardiovascular morbidity and mortality. Healthy behavioural modification is the cornerstone for reducing the atherosclerotic cardiovascular disease burden in this population. Comprehensive, multi-disciplinary cardiac rehabilitation (CR) programs reduce mortality and hospitalizations in patients with MetS and DM. Despite this benefit, patients with MetS and DM are less likely to attend and complete CR because of numerous barriers. Implementation of innovative CR delivery models might improve utilization of CR and cardiovascular outcomes in this high-risk population. PMID:27692115

  9. A global comprehensive review of economic interventions to prevent intimate partner violence and HIV risk behaviours.

    PubMed

    Gibbs, Andrew; Jacobson, Jessica; Kerr Wilson, Alice

    Intimate partner violence (IPV) and HIV are co-occurring global epidemics, with similar root causes of gender and economic inequalities. Economic interventions have become a central approach to preventing IPV and HIV. We undertook a comprehensive scoping review of published evaluations of economic interventions that sought to prevent IPV and/or HIV risk behaviours. Forty-five separate analyses of interventions met our criteria. Broadly, unconditional cash transfer interventions showed either flat or positive outcomes; economic strengthening interventions had mixed outcomes, with some negative, flat and positive results reported; interventions combining economic strengthening and gender transformative interventions tended to have positive outcomes. The review highlighted a number of gaps. Specifically, there were limited studies evaluating the impact of economic interventions on female sex workers, young women, and men. In addition, there were missed opportunities, with many evaluations only reporting either IPV- or HIV-related outcomes, rather than both, despite overlaps.

  10. Radiation risk and human space exploration

    NASA Technical Reports Server (NTRS)

    Schimmerling, W.; Cucinotta, F. A.; Wilson, J. W.

    2003-01-01

    Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented. Published by Elsevier Science Ltd on behalf of COSPAR.

  11. Radiation risk and human space exploration.

    PubMed

    Schimmerling, W; Cucinotta, F A; Wilson, J W

    2003-01-01

    Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented.

  12. Radiation risk and human space exploration

    NASA Technical Reports Server (NTRS)

    Schimmerling, W.; Cucinotta, F. A.; Wilson, J. W.

    2003-01-01

    Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented. Published by Elsevier Science Ltd on behalf of COSPAR.

  13. Developing a Comprehensive Risk Assessment Framework for Geological Storage CO2

    SciTech Connect

    Duncan, Ian

    2014-08-31

    from pipelines or wells are arguably the highest risk aspects of CO2 enhanced oil recovery (CO2-EOR), carbon capture, and storage (CCS). Assertions in the CCS literature, that CO2 levels of 10% for ten minutes, or 20 to 30% for a few minutes are lethal to humans, are not supported by the available evidence. The results of published experiments with animals exposed to CO2, from mice to monkeys, at both normal and depleted oxygen levels, suggest that lethal levels of CO2 toxicity are in the range 50 to 60%. These experiments demonstrate that CO2 does not kill by asphyxia, but rather is toxic at high concentrations. It is concluded that quantitative risk assessments of CCS have overestimated the risk of fatalities by using values of lethality a factor two to six lower than the values estimated in this paper. In many dispersion models of CO2 releases from pipelines, no fatalities would be predicted if appropriate levels of lethality for CO2 had been used in the analysis.

  14. Comprehensive Review of the Impact of Dairy Foods and Dairy Fat on Cardiometabolic Risk.

    PubMed

    Drouin-Chartier, Jean-Philippe; Côté, Julie Anne; Labonté, Marie-Ève; Brassard, Didier; Tessier-Grenier, Maude; Desroches, Sophie; Couture, Patrick; Lamarche, Benoît

    2016-11-01

    Because regular-fat dairy products are a major source of cholesterol-raising saturated fatty acids (SFAs), current US and Canadian dietary guidelines for cardiovascular health recommend the consumption of low-fat dairy products. Yet, numerous randomized controlled trials (RCTs) have reported rather mixed effects of reduced- and regular-fat dairy consumption on blood lipid concentrations and on many other cardiometabolic disease risk factors, such as blood pressure and inflammation markers. Thus, the focus on low-fat dairy in current dietary guidelines is being challenged, creating confusion within health professional circles and the public. This narrative review provides perspective on the research pertaining to the impact of dairy consumption and dairy fat on traditional and emerging cardiometabolic disease risk factors. This comprehensive assessment of evidence from RCTs suggests that there is no apparent risk of potential harmful effects of dairy consumption, irrespective of the content of dairy fat, on a large array of cardiometabolic variables, including lipid-related risk factors, blood pressure, inflammation, insulin resistance, and vascular function. This suggests that the purported detrimental effects of SFAs on cardiometabolic health may in fact be nullified when they are consumed as part of complex food matrices such as those in cheese and other dairy foods. Thus, the focus on low-fat dairy products in current guidelines apparently is not entirely supported by the existing literature and may need to be revisited on the basis of this evidence. Future studies addressing key research gaps in this area will be extremely informative to better appreciate the impact of dairy food matrices, as well as dairy fat specifically, on cardiometabolic health.

  15. Mineral oil in human tissues, part II: characterization of the accumulated hydrocarbons by comprehensive two-dimensional gas chromatography.

    PubMed

    Biedermann, Maurus; Barp, Laura; Kornauth, Christoph; Würger, Tanja; Rudas, Margaretha; Reiner, Angelika; Concin, Nicole; Grob, Koni

    2015-02-15

    Mineral oil hydrocarbons are by far the largest contaminant in the human body. Their composition differs from that in the mineral oils humans are exposed to, and varies also between different tissues of the same individual. Using the presently best technique for characterizing the composition of mineral oil hydrocarbons, comprehensive two-dimensional gas chromatography (GC×GC), the hydrocarbons in human tissues were compared to those of various mineral oils. This provided information about the strongly accumulated species and might give hints on the flow path through the human body. The selectivity of accumulation is probably also of interest for the risk assessment of synthetic hydrocarbons (polyolefins). GC×GC grouped the MOSH into classes of n-alkanes, paraffins with a low degree of branching, multibranched paraffins and naphthenes (alkylated cyclic hydrocarbons) with 1-4 rings. Metabolic elimination was observed for constituents of all these classes, but was selective within each class. The MOSH in the subcutaneous abdominal fat tissues and the mesenteric lymph nodes (MLN) had almost the same composition and included the distinct signals observed in mineral oil, though in reduced amounts relative to the cloud of unresolved hydrocarbons. The MOSH in the liver and the spleen were different from those in the MLN and fat tissue, but again with largely identical composition for a given individual. Virtually all constituents forming distinct signals were eliminated, leaving an unresolved residue of highly isomerized hydrocarbons.

  16. Improving environmental risk assessment of human pharmaceuticals.

    PubMed

    Ågerstrand, Marlene; Berg, Cecilia; Björlenius, Berndt; Breitholtz, Magnus; Brunström, Björn; Fick, Jerker; Gunnarsson, Lina; Larsson, D G Joakim; Sumpter, John P; Tysklind, Mats; Rudén, Christina

    2015-05-05

    This paper presents 10 recommendations for improving the European Medicines Agency's guidance for environmental risk assessment of human pharmaceutical products. The recommendations are based on up-to-date, available science in combination with experiences from other chemical frameworks such as the REACH-legislation for industrial chemicals. The recommendations concern: expanding the scope of the current guideline; requirements to assess the risk for development of antibiotic resistance; jointly performed assessments; refinement of the test proposal; mixture toxicity assessments on active pharmaceutical ingredients with similar modes of action; use of all available ecotoxicity studies; mandatory reviews; increased transparency; inclusion of emission data from production; and a risk management option. We believe that implementation of our recommendations would strengthen the protection of the environment and be beneficial to society. Legislation and guidance documents need to be updated at regular intervals in order to incorporate new knowledge from the scientific community. This is particularly important for regulatory documents concerning pharmaceuticals in the environment since this is a research field that has been growing substantially in the last decades.

  17. A comparison and appraisal of a comprehensive range of human thermal climate indices

    NASA Astrophysics Data System (ADS)

    de Freitas, C. R.; Grigorieva, E. A.

    2016-08-01

    Numerous human thermal climate indices have been proposed. It is a manifestation of the perceived importance of the thermal environment within the scientific community and a desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, and the particular design for application. They also vary considerably in type and quality, method used to express output, as well as in several other aspects. In light of this, a three-stage project was undertaken to deliver a comprehensive documentation, classification, and overall evaluation of the full range of existing human thermal climate indices. The first stage of the project produced a comprehensive register of as many thermal indices as could be found, 165 in all. The second stage devised a sorting scheme of these human thermal climate indices that grouped them according to eight primary classification categories. This, the third stage of the project, evaluates the indices. Six evaluation criteria, namely validity, usability, transparency, sophistication, completeness, and scope, are used collectively as evaluation criteria to rate each index scheme. The evaluation criteria are used to assign a score that varies between 1 and 5, 5 being the highest. The indices with the highest in each of the eight primary classification categories are discussed. The work is the final stage of a study of the all human thermal climatic indices that could be found in literature. Others have considered the topic, but this study is the first detailed, genuinely comprehensive, and systematic comparison. The results make it simpler to locate and compare indices. It is now easier for users to reflect on the merits of all available thermal indices and decide which is most suitable for a particular application or investigation.

  18. A comparison and appraisal of a comprehensive range of human thermal climate indices.

    PubMed

    de Freitas, C R; Grigorieva, E A

    2017-03-01

    Numerous human thermal climate indices have been proposed. It is a manifestation of the perceived importance of the thermal environment within the scientific community and a desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, and the particular design for application. They also vary considerably in type and quality, method used to express output, as well as in several other aspects. In light of this, a three-stage project was undertaken to deliver a comprehensive documentation, classification, and overall evaluation of the full range of existing human thermal climate indices. The first stage of the project produced a comprehensive register of as many thermal indices as could be found, 165 in all. The second stage devised a sorting scheme of these human thermal climate indices that grouped them according to eight primary classification categories. This, the third stage of the project, evaluates the indices. Six evaluation criteria, namely validity, usability, transparency, sophistication, completeness, and scope, are used collectively as evaluation criteria to rate each index scheme. The evaluation criteria are used to assign a score that varies between 1 and 5, 5 being the highest. The indices with the highest in each of the eight primary classification categories are discussed. The work is the final stage of a study of the all human thermal climatic indices that could be found in literature. Others have considered the topic, but this study is the first detailed, genuinely comprehensive, and systematic comparison. The results make it simpler to locate and compare indices. It is now easier for users to reflect on the merits of all available thermal indices and decide which is most suitable for a particular application or investigation.

  19. A comparison and appraisal of a comprehensive range of human thermal climate indices

    NASA Astrophysics Data System (ADS)

    de Freitas, C. R.; Grigorieva, E. A.

    2017-03-01

    Numerous human thermal climate indices have been proposed. It is a manifestation of the perceived importance of the thermal environment within the scientific community and a desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, and the particular design for application. They also vary considerably in type and quality, method used to express output, as well as in several other aspects. In light of this, a three-stage project was undertaken to deliver a comprehensive documentation, classification, and overall evaluation of the full range of existing human thermal climate indices. The first stage of the project produced a comprehensive register of as many thermal indices as could be found, 165 in all. The second stage devised a sorting scheme of these human thermal climate indices that grouped them according to eight primary classification categories. This, the third stage of the project, evaluates the indices. Six evaluation criteria, namely validity, usability, transparency, sophistication, completeness, and scope, are used collectively as evaluation criteria to rate each index scheme. The evaluation criteria are used to assign a score that varies between 1 and 5, 5 being the highest. The indices with the highest in each of the eight primary classification categories are discussed. The work is the final stage of a study of the all human thermal climatic indices that could be found in literature. Others have considered the topic, but this study is the first detailed, genuinely comprehensive, and systematic comparison. The results make it simpler to locate and compare indices. It is now easier for users to reflect on the merits of all available thermal indices and decide which is most suitable for a particular application or investigation.

  20. Population Structure in a Comprehensive Genomic Data Set on Human Microsatellite Variation

    PubMed Central

    Pemberton, Trevor J.; DeGiorgio, Michael; Rosenberg, Noah A.

    2013-01-01

    Over the past two decades, microsatellite genotypes have provided the data for landmark studies of human population-genetic variation. However, the various microsatellite data sets have been prepared with different procedures and sets of markers, so that it has been difficult to synthesize available data for a comprehensive analysis. Here, we combine eight human population-genetic data sets at the 645 microsatellite loci they share in common, accounting for procedural differences in the production of the different data sets, to assemble a single data set containing 5795 individuals from 267 worldwide populations. We perform a systematic analysis of genetic relatedness, detecting 240 intra-population and 92 inter-population pairs of previously unidentified close relatives and proposing standardized subsets of unrelated individuals for use in future studies. We then augment the human data with a data set of 84 chimpanzees at the 246 loci they share in common with the human samples. Multidimensional scaling and neighbor-joining analyses of these data sets offer new insights into the structure of human populations and enable a comparison of genetic variation patterns in chimpanzees with those in humans. Our combined data sets are the largest of their kind reported to date and provide a resource for use in human population-genetic studies. PMID:23550135

  1. Comprehensive national database of tree effects on air quality and human health in the United States.

    PubMed

    Hirabayashi, Satoshi; Nowak, David J

    2016-08-01

    Trees remove air pollutants through dry deposition processes depending upon forest structure, meteorology, and air quality that vary across space and time. Employing nationally available forest, weather, air pollution and human population data for 2010, computer simulations were performed for deciduous and evergreen trees with varying leaf area index for rural and urban areas in every county in the conterminous United States. The results populated a national database of annual air pollutant removal, concentration changes, and reductions in adverse health incidences and costs for NO2, O3, PM2.5 and SO2. The developed database enabled a first order approximation of air quality and associated human health benefits provided by trees with any forest configurations anywhere in the conterminous United States over time. Comprehensive national database of tree effects on air quality and human health in the United States was developed.

  2. A comprehensive model of human ear for analysis of implantable hearing devices.

    PubMed

    Zhang, Xiangming; Gan, Rong Z

    2011-10-01

    A finite element (FE) model of the human ear including the ear canal, middle ear, and spiral cochlea was constructed from histological sections of human temporal bone. Multiphysics analysis of the acoustics, structure, and fluid coupling in the ear was conducted in the model. The viscoelastic material behavior was applied to the middle ear soft tissues based on dynamic measurements of tissues in our laboratory. The FE model was first validated using the experimental data obtained in human cadaver ears, and then used to investigate the efficiency of the forward and reverse mechanical driving with middle ear implant, and the passive vibration of basilar membrane (BM) with cochlear implant placed in the cochlear scala tympani. The middle ear transfer function and the cochlear function of the BM vibration were derived from the model. This comprehensive ear model provides a novel computational tool to visualize and compute the implantable hearing devices and surgical procedures.

  3. Human scenarios for the screening assessment. Columbia River Comprehensive Impact Assessment

    SciTech Connect

    Napier, B.A.; Harper, B.L.; Lane, N.K.; Strenge, D.L.; Spivey, R.B.

    1996-03-01

    Because of past nuclear production operations along the Columbia River, there is intense public and tribal interest in assessing any residual Hanford Site related contamination along the river from the Hanford Reach to the Pacific Ocean. The Columbia River Impact Assessment (CRCIA) was proposed to address these concerns. The assessment of the Columbia River is being conducted in phases. The initial phase is a screening assessment of risk, which addresses current environmental conditions for a range of potential uses. One component of the screening assessment estimates the risk from contaminants in the Columbia River to humans. Because humans affected by the Columbia river are involved in a wide range of activities, various scenarios have been developed on which to base the risk assessments. The scenarios illustrate the range of activities possible by members of the public coming in contact with the Columbia River so that the impact of contaminants in the river on human health can be assessed. Each scenario illustrates particular activity patterns by a specific group. Risk will be assessed at the screening level for each scenario. This report defines the scenarios and the exposure factors that will be the basis for estimating the potential range of risk to human health from Hanford-derived radioactive as well as non-radioactive contaminants associated with the Columbia River.

  4. Guidelines on the scope, content, and use of comprehensive risk assessment in the management of high-level nuclear waste transportation

    SciTech Connect

    Golding, D.; White, A.

    1990-12-01

    This report discusses the scope of risk assessment strategies in the management of the transport of high-level radioactive wastes. In spite of the shortcomings of probabilistic risk assessment(PRA), the Transportation Needs Assessment recommended this as the preferred methodology to assess the risks of high level nuclear waste (HLNW) transportation. A PRA also will need to heed the lessons learned from the development and application of PRA elsewhere, such as in the nuclear power industry. A set of guidelines will aid this endeavor by outlining the appropriate scope, content, and use of a risk assessment which is more responsive to the uncertainties, human-technical interactions, social forces, and iterative relationship with risk management strategies, than traditional PRAS. This more expansive definition, which encompasses but is not totally reliant on rigorous data requirements and quantitative probability estimates, we term Comprehensive Risk Assessment (CRA) Guidelines will be developed in three areas: the limitations of existing methodologies and suggested modifications; CRA as part of a flexible, effective, adaptive risk management system for HLNW transportation; and, the use of CRA in risk communication.

  5. [Health risks and economic costs associated with obesity requiring a comprehensive weight reduction program].

    PubMed

    Hainer, V; Kunesová, M; Parízková, J; Stunkard, A

    1997-06-12

    An increasing prevalence of obesity all over the world reflects a lack of effective measures in both prevention and treatment of obesity. Obesity as a disease has been underestimated by the lay-public as well as health care providers. However, obesity represents a substantial health problem associated with a decreased quality of life. Obesity is linked to numerous chronic diseases (cardiovascular diseases, diabetes, hyperlipidemia, gout, osteoarthritis, gall-stones, and bowel, breast and genitourinary cancers) that lead to premature disability and mortality. Health risks increase with a body mass index (BMI) over 25 in individuals 19-35 years of age and with a BMI over 27 in those 35 years of age and older. Health risks also increase with an excess accumulation of visceral fat manifested as an increase in waist circumference (> 100 cm) or in waist to hip ratio (> 0.85 for females and > 1.00 for males). According to studies carried out in different countries current economic costs of obesity represent 5-8% of all direct health costs. In contrast, effective treatment of obesity results in a substantial decrease in expenditures associated with pharmacotherapy of hypertension, diabetes, hyperlipidemia and osteoarthritis. Both scientists and clinicians involved in obesity research and treatment recommend to introduce the long-term weight management programs focussing more on the overall health of the participants than the weight loss per se. Therefore, it will be necessary to establish new realistic goals in the obesity management that reflect reasonable weights and recently experienced beneficial health effects of modest (5-10%) weight loss. Comprehensive obesity treatment consisting of low fat diet, exercise, behavioral modification, drug therapy and surgical procedures requires differentiated weight management programs modified according to the degree and type of obesity as well as to current health complications present. The Czech Society for the Study of Obesity

  6. NEUROBEHAVIORAL TESTING IN HUMAN RISK ASSESSMENT

    PubMed Central

    Rohlman, Diane S.; Lucchini, Roberto; Anger, W. Kent; Bellinger, David C.; van Thriel, Christoph

    2008-01-01

    Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. The field of neurobehavioral toxicology has evolved from research which initially focused on using traditional neuropsychological tests to identify “abnormal cases” to include methods used to detect sub-clinical deficits, to further incorporate the use of neurosensory assessment, and to expand testing from occupational populations to vulnerable populations including older adults and children. Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations. This paper reflects a summary of the talks presented at the symposium presented at the 11th meeting of the International Neurotoxicology Association. PMID:18539229

  7. Exploring Students at Risk for Reading Comprehension Difficulties in South Korea: The RTI Approach Applying Latent Class Growth Analysis

    ERIC Educational Resources Information Center

    Kim, Dongil; Kim, Woori; Koh, Hyejung; Lee, Jaeho; Shin, Jaehyun; Kim, Heeju

    2014-01-01

    The purpose of this study was to identify students at risk of reading comprehension difficulties by using the responsiveness to intervention (RTI) approach. The participants were 177 students in Grades 1-3 in three elementary schools in South Korea. The students received Tier 1 instruction of RTI from March to May 2011, and their performance was…

  8. Exploring Students at Risk for Reading Comprehension Difficulties in South Korea: The RTI Approach Applying Latent Class Growth Analysis

    ERIC Educational Resources Information Center

    Kim, Dongil; Kim, Woori; Koh, Hyejung; Lee, Jaeho; Shin, Jaehyun; Kim, Heeju

    2014-01-01

    The purpose of this study was to identify students at risk of reading comprehension difficulties by using the responsiveness to intervention (RTI) approach. The participants were 177 students in Grades 1-3 in three elementary schools in South Korea. The students received Tier 1 instruction of RTI from March to May 2011, and their performance was…

  9. Improving Reading Comprehension through Holistic Intervening and Tutoring During After-School with High Risk Minority Elementary School Students

    ERIC Educational Resources Information Center

    Johnson, Kaprea F.; Gupta, Abha; Rosen, Hana; Rosen, Howard

    2013-01-01

    The current study took a quasi-experimental approach investigating the effect of a holistic after-school intervention, on reading comprehension measured by the Gray Oral Reading Test (GORT)-4 on at-risk students in Grade 2 through Grade 5. Analysis of Variance was used to investigate the relationship between pre- and post-intervention scores. The…

  10. Improving Reading Comprehension through Holistic Intervening and Tutoring During After-School with High Risk Minority Elementary School Students

    ERIC Educational Resources Information Center

    Johnson, Kaprea F.; Gupta, Abha; Rosen, Hana; Rosen, Howard

    2013-01-01

    The current study took a quasi-experimental approach investigating the effect of a holistic after-school intervention, on reading comprehension measured by the Gray Oral Reading Test (GORT)-4 on at-risk students in Grade 2 through Grade 5. Analysis of Variance was used to investigate the relationship between pre- and post-intervention scores. The…

  11. Redesigning Care For Patients At Increased Hospitalization Risk: The Comprehensive Care Physician Model

    PubMed Central

    Meltzer, David O.; Ruhnke, Gregory W.

    2015-01-01

    Patients who have been hospitalized often experience care coordination problems that worsen outcomes and increase costs. One reason is that hospital care and ambulatory care are often provided by different physicians. However, interventions to improve care coordination for hospitalized patients have not consistently improved outcomes and generally have not reduced costs. We describe the rationale for the Comprehensive Care Physician model, in which physicians focus their practice on patients at increased risk of hospitalization so that they can provide both inpatient and outpatient care to their patients. We also describe the design and implementation of a study supported by the Center for Medicare and Medicaid Innovation to assess the model’s effects on costs and outcomes. Evidence concerning the effectiveness of the program is expected by 2016. If the program is found to be effective, the next steps will be to assess the durability of its benefits and the model’s potential for dissemination; evidence to the contrary will provide insights into how to alter the program to address sources of failure. PMID:24799573

  12. Risk Assessment for Human Immunodeficiency Virus among Pregnant Hispanic Adolescents.

    ERIC Educational Resources Information Center

    Berger, David K.; And Others

    1993-01-01

    Assessed human immunodeficiency virus (HIV) risk status of pregnant Hispanic adolescents in New York City. One-third of 87 adolescents were identified as being at increased risk for HIV infection. Sexual risk-taking behavior was most common factor that increased HIV risk. Birthplace and nationality were significantly associated with HIV risk…

  13. Human Health Risk Assessment Research Strategy. External Review Draft.

    DTIC Science & Technology

    1998-02-01

    magnitude greater than the environmental exposure for which estimates of risk are 5 being made, as well as from test animals to humans. The uncertainties in...such extrapolations are 6 considerable and represent major problems facing the risk assessor. 7 Extrapolation from animal data to estimate human...risks involves a variety of assumptions 8 about interspecies differences between animals and humans. 9 Extrapolation from high to low dose from either

  14. Comprehensiveness and humanization of nursing care management in the Intensive Care Unit.

    PubMed

    Medeiros, Adriane Calvetti de; Siqueira, Hedi Crecencia Heckler de; Zamberlan, Claudia; Cecagno, Diana; Nunes, Simone Dos Santos; Thurow, Mara Regina Bergmann

    2016-01-01

    Identifying the elements that promote comprehensiveness and humanization of nursing care management in the Intensive Care Unit, with an ecosystemic approach. A documentary qualitative study. The method of documentary analysis was used for data analysis. Four pre-established categories were identified - Technical; Organizational; Technological; and Humanizing Dimensions. Data resulted in forming two sub-categories that integrate the humanizing dimension category, namely 'Comprehensiveness in healthcare actions' and 'Integrating processes and promoters of humanization,' bringing forth implications and challenges in forms of managing health work processes, enabling organizational, structural and managerial changes to the provided healthcare. It was considered that all structural elements in managing nursing care with a focus on the needs of users should be in line with public policies and the principles of comprehensiveness and humanization, thus possessing strong potential for transforming health practices. Identificar os elementos capazes de promover a integralidade e a humanização na gestão do cuidado de enfermagem na Unidade de Terapia Intensiva, com enfoque ecossistêmico. Pesquisa documental, de natureza qualitativa. Para a análise dos dados utilizou-se do método da análise documental. SForam identificadas quatro categorias preestabelecidas ‒ Dimensões: Técnica; Organizacional; Tecnológica e Humanizadora. Os dados resultantes das duas subcategorias que integraram a categoria Dimensão Humanizadora, Integralidade nas ações do cuidado e Processos integradores e promotores de humanização, trazem implicações e desafios nos modos de gerir os processos de trabalho em saúde, o que possibilita transformações organizacionais, estruturais e gerenciais na produção do cuidado. Considera-se que na gestão do cuidado de enfermagem todos os elementos estruturantes, com enfoque nas necessidades dos usuários, devem estar em consonância com as políticas p

  15. Human-tiger conflict: a review and call for comprehensive plans.

    PubMed

    Goodrich, John M

    2010-12-01

    Human-tiger (Panthera tigris Linnaeus, 1758) conflicts (HTC), manifested primarily as attacks on people and domestic animals, exacerbate at least 2 major threats to tigers: (i) conflicts often result in mortality or removal of tigers from the wild; and (ii) they result in negative attitudes towards tigers by local people, thereby reducing support for tiger conservation. Although HTC has decreased over the past century, it will likely increase if current and proposed conservation initiatives to double tiger populations are successful. Increased HTC could undermine successful conservation initiatives if proactive steps are not taken to reduce HTC. The present paper provides a review of the impacts of HTC and the measures taken to reduce it in ways that reduce negative impacts on both humans and tigers, and stresses the need for development and implementation of comprehensive plans to reduce HTC. © 2010 ISZS, Blackwell Publishing and IOZ/CAS.

  16. A Comprehensive Library of Familial Human Amyotrophic Lateral Sclerosis Induced Pluripotent Stem Cells

    PubMed Central

    Li, Ying; Balasubramanian, Umamahesw; Cohen, Devon; Zhang, Ping-Wu; Mosmiller, Elizabeth; Sattler, Rita; Maragakis, Nicholas J.; Rothstein, Jeffrey D.

    2015-01-01

    Amyotrophic lateral sclerosis is a progressive disease characterized by the loss of upper and lower motor neurons, leading to paralysis of voluntary muscles. About 10% of all ALS cases are familial (fALS), among which 15–20% are linked to Cu/Zn superoxide dismutase (SOD1) mutations, usually inherited in an autosomal dominant manner. To date only one FDA approved drug is available which increases survival moderately. Our understanding of ALS disease mechanisms is largely derived from rodent model studies, however due to the differences between rodents and humans, it is necessary to have humanized models for studies of disease pathogenesis as well as drug development. Therefore, we generated a comprehensive library of a total 22 of fALS patient-specific induced pluripotent stem cell (iPSC) lines. These cells were thoroughly characterized before being deposited into the library. The library of cells includes a variety of C9orf72 mutations, sod1 mutations, FUS, ANG and FIG4 mutations. Certain mutations are represented with more than one line, which allows for studies of variable genetic backgrounds. In addition, these iPSCs can be successfully differentiated to astroglia, a cell type known to play a critical role in ALS disease progression. This library represents a comprehensive resource that can be used for ALS disease modeling and the development of novel therapeutics. PMID:25760436

  17. A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear.

    PubMed

    Schrauwen, Isabelle; Hasin-Brumshtein, Yehudit; Corneveaux, Jason J; Ohmen, Jeffrey; White, Cory; Allen, April N; Lusis, Aldons J; Van Camp, Guy; Huentelman, Matthew J; Friedman, Rick A

    2016-03-01

    The mammalian inner ear consists of the cochlea and the vestibular labyrinth (utricle, saccule, and semicircular canals), which participate in both hearing and balance. Proper development and life-long function of these structures involves a highly complex coordinated system of spatial and temporal gene expression. The characterization of the inner ear transcriptome is likely important for the functional study of auditory and vestibular components, yet, primarily due to tissue unavailability, detailed expression catalogues of the human inner ear remain largely incomplete. We report here, for the first time, comprehensive transcriptome characterization of the adult human cochlea, ampulla, saccule and utricle of the vestibule obtained from patients without hearing abnormalities. Using RNA-Seq, we measured the expression of >50,000 predicted genes corresponding to approximately 200,000 transcripts, in the adult inner ear and compared it to 32 other human tissues. First, we identified genes preferentially expressed in the inner ear, and unique either to the vestibule or cochlea. Next, we examined expression levels of specific groups of potentially interesting RNAs, such as genes implicated in hearing loss, long non-coding RNAs, pseudogenes and transcripts subject to nonsense mediated decay (NMD). We uncover the spatial specificity of expression of these RNAs in the hearing/balance system, and reveal evidence of tissue specific NMD. Lastly, we investigated the non-syndromic deafness loci to which no gene has been mapped, and narrow the list of potential candidates for each locus. These data represent the first high-resolution transcriptome catalogue of the adult human inner ear. A comprehensive identification of coding and non-coding RNAs in the inner ear will enable pathways of auditory and vestibular function to be further defined in the study of hearing and balance. Expression data are freely accessible at https://www.tgen.org/home/research/research-divisions/neurogenomics/supplementary-data/inner-ear-transcriptome.aspx.

  18. A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear

    PubMed Central

    Corneveaux, Jason J.; Ohmen, Jeffrey; White, Cory; Allen, April N.; Lusis, Aldons J.; Van Camp, Guy; Huentelman, Matthew J.; Friedman, Rick A.

    2015-01-01

    The mammalian inner ear consists of the cochlea and the vestibular labyrinth (utricle, saccule, and semicircular canals), which participate in both hearing and balance. Proper development and life-long function of these structures involves a highly complex coordinated system of spatial and temporal gene expression. The characterization of the inner ear transcriptome is likely important for the functional study of auditory and vestibular components, yet, primarily due to tissue unavailability, detailed expression catalogues of the human inner ear remain largely incomplete. We report here, for the first time, comprehensive transcriptome characterization of the adult human cochlea, ampulla, saccule and utricle of the vestibule obtained from patients without hearing abnormalities. Using RNA-Seq, we measured the expression of >50,000 predicted genes corresponding to approximately 200,000 transcripts, in the adult inner ear and compared it to 32 other human tissues. First, we identified genes preferentially expressed in the inner ear, and unique either to the vestibule or cochlea. Next, we examined expression levels of specific groups of potentially interesting RNAs, such as genes implicated in hearing loss, long non-coding RNAs, pseudogenes and transcripts subject to nonsense mediated decay (NMD). We uncover the spatial specificity of expression of these RNAs in the hearing/balance system, and reveal evidence of tissue specific NMD. Lastly, we investigated the non-syndromic deafness loci to which no gene has been mapped, and narrow the list of potential candidates for each locus. These data represent the first high-resolution transcriptome catalogue of the adult human inner ear. A comprehensive identification of coding and non-coding RNAs in the inner ear will enable pathways of auditory and vestibular function to be further defined in the study of hearing and balance. Expression data are freely accessible at https://www.tgen.org/home/research

  19. Developing a comprehensive approach to risk management of musculoskeletal disorders in non-nursing health care sector employees.

    PubMed

    Oakman, Jodi; Macdonald, Wendy; Wells, Yvonne

    2014-11-01

    This study of selected jobs in the health care sector explored a range of physical and psychosocial factors to identify those that most strongly predicted work-related musculoskeletal disorders (WMSD) risk. A self-report survey was used to collect data on physical and psychosocial risk factors from employees in three health care organisations in Victoria, Australia. Multivariate analyses demonstrated the importance of both psychosocial and physical hazards in predicting WMSD risk and provides evidence for risk management of WMSDs to incorporate a more comprehensive and integrated approach. Use of a risk management toolkit is recommended to address WMSD risk in the workplace. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  20. Human Transporter Database: Comprehensive Knowledge and Discovery Tools in the Human Transporter Genes

    PubMed Central

    Ye, Adam Y.; Liu, Qing-Rong; Li, Chuan-Yun; Zhao, Min; Qu, Hong

    2014-01-01

    Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD) (http://htd.cbi.pku.edu.cn). Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine. PMID:24558441

  1. A Framework for Assessing Uncertainty Associated with Human Health Risks from MSW Landfill Leachate Contamination.

    PubMed

    Mishra, Harshit; Karmakar, Subhankar; Kumar, Rakesh; Singh, Jitendra

    2016-09-24

    Landfilling is a cost-effective method, which makes it a widely used practice around the world, especially in developing countries. However, because of the improper management of landfills, high leachate leakage can have adverse impacts on soils, plants, groundwater, aquatic organisms, and, subsequently, human health. A comprehensive survey of the literature finds that the probabilistic quantification of uncertainty based on estimations of the human health risks due to landfill leachate contamination has rarely been reported. Hence, in the present study, the uncertainty about the human health risks from municipal solid waste landfill leachate contamination to children and adults was quantified to investigate its long-term risks by using a Monte Carlo simulation framework for selected heavy metals. The Turbhe sanitary landfill of Navi Mumbai, India, which was commissioned in the recent past, was selected to understand the fate and transport of heavy metals in leachate. A large residential area is located near the site, which makes the risk assessment problem both crucial and challenging. In this article, an integral approach in the form of a framework has been proposed to quantify the uncertainty that is intrinsic to human health risk estimation. A set of nonparametric cubic splines was fitted to identify the nonlinear seasonal trend in leachate quality parameters. LandSim 2.5, a landfill simulator, was used to simulate the landfill activities for various time slices, and further uncertainty in noncarcinogenic human health risk was estimated using a Monte Carlo simulation followed by univariate and multivariate sensitivity analyses.

  2. Risk and the evolution of human exchange

    PubMed Central

    Kaplan, Hillard S.; Schniter, Eric; Smith, Vernon L.; Wilson, Bart J.

    2012-01-01

    Compared with other species, exchange among non-kin is a hallmark of human sociality in both the breadth of individuals and total resources involved. One hypothesis is that extensive exchange evolved to buffer the risks associated with hominid dietary specialization on calorie dense, large packages, especially from hunting. ‘Lucky’ individuals share food with ‘unlucky’ individuals with the expectation of reciprocity when roles are reversed. Cross-cultural data provide prima facie evidence of pair-wise reciprocity and an almost universal association of high-variance (HV) resources with greater exchange. However, such evidence is not definitive; an alternative hypothesis is that food sharing is really ‘tolerated theft’, in which individuals possessing more food allow others to steal from them, owing to the threat of violence from hungry individuals. Pair-wise correlations may reflect proximity providing greater opportunities for mutual theft of food. We report a laboratory experiment of foraging and food consumption in a virtual world, designed to test the risk-reduction hypothesis by determining whether people form reciprocal relationships in response to variance of resource acquisition, even when there is no external enforcement of any transfer agreements that might emerge. Individuals can forage in a high-mean, HV patch or a low-mean, low-variance (LV) patch. The key feature of the experimental design is that individuals can transfer resources to others. We find that sharing hardly occurs after LV foraging, but among HV foragers sharing increases dramatically over time. The results provide strong support for the hypothesis that people are pre-disposed to evaluate gains from exchange and respond to unsynchronized variance in resource availability through endogenous reciprocal trading relationships. PMID:22513855

  3. The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases.

    PubMed

    Szeverenyi, Ildiko; Cassidy, Andrew J; Chung, Cheuk Wang; Lee, Bernett T K; Common, John E A; Ogg, Stephen C; Chen, Huijia; Sim, Shu Yin; Goh, Walter L P; Ng, Kee Woei; Simpson, John A; Chee, Li Lian; Eng, Goi Hui; Li, Bin; Lunny, Declan P; Chuon, Danny; Venkatesh, Aparna; Khoo, Kian Hoe; McLean, W H Irwin; Lim, Yun Ping; Lane, E Birgitte

    2008-03-01

    We describe a revised and expanded database on human intermediate filament proteins, a major component of the eukaryotic cytoskeleton. The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. To date, the database catalogs 1,274 manually-curated pathogenic sequence variants and 170 allelic variants in intermediate filament genes from over 459 peer-reviewed research articles. Unrelated cases were collected from all of the six sequence homology groups and the sequence variations were described at cDNA and protein levels with links to the related diseases and reference articles. The mutations and polymorphisms are presented in parallel with data on protein structure, gene, and chromosomal location and basic information on associated diseases. Detailed statistics relating to the variants records in the database are displayed by homology group, mutation type, affected domain, associated diseases, and nucleic and amino acid substitutions. Multiple sequence alignment algorithms can be run from queries to determine DNA or protein sequence conservation. Literature sources can be interrogated within the database and external links are provided to public databases. The database is freely and publicly accessible online at www.interfil.org (last accessed 13 September 2007). Users can query the database by various keywords and the search results can be downloaded. It is anticipated that the Human Intermediate Filament Database (HIFD) will provide a useful resource to study human genome variations for basic scientists, clinicians, and students alike.

  4. REDIportal: a comprehensive database of A-to-I RNA editing events in humans

    PubMed Central

    Picardi, Ernesto; D'Erchia, Anna Maria; Lo Giudice, Claudio; Pesole, Graziano

    2017-01-01

    RNA editing by A-to-I deamination is the prominent co-/post-transcriptional modification in humans. It is carried out by ADAR enzymes and contributes to both transcriptomic and proteomic expansion. RNA editing has pivotal cellular effects and its deregulation has been linked to a variety of human disorders including neurological and neurodegenerative diseases and cancer. Despite its biological relevance, many physiological and functional aspects of RNA editing are yet elusive. Here, we present REDIportal, available online at http://srv00.recas.ba.infn.it/atlas/, the largest and comprehensive collection of RNA editing in humans including more than 4.5 millions of A-to-I events detected in 55 body sites from thousands of RNAseq experiments. REDIportal embeds RADAR database and represents the first editing resource designed to answer functional questions, enabling the inspection and browsing of editing levels in a variety of human samples, tissues and body sites. In contrast with previous RNA editing databases, REDIportal comprises its own browser (JBrowse) that allows users to explore A-to-I changes in their genomic context, empathizing repetitive elements in which RNA editing is prominent. PMID:27587585

  5. Comprehensive Red List Assessment Reveals Exceptionally High Extinction Risk to Madagascar Palms

    PubMed Central

    Rakotoarinivo, Mijoro; Dransfield, John; Bachman, Steven P.; Moat, Justin; Baker, William J.

    2014-01-01

    The establishment of baseline IUCN Red List assessments for plants is a crucial step in conservation planning. Nowhere is this more important than in biodiversity hotspots that are subject to significant anthropogenic pressures, such as Madagascar. Here, all Madagascar palm species are assessed using the IUCN Red List categories and criteria, version 3.1. Our results indicate that 83% of the 192 endemic species are threatened, nearly four times the proportion estimated for plants globally and exceeding estimates for all other comprehensively evaluated plant groups in Madagascar. Compared with a previous assessment in 1995, the number of Endangered and Critically Endangered species has substantially increased, due to the discovery of 28 new species since 1995, most of which are highly threatened. The conservation status of most species included in both the 1995 and the current assessments has not changed. Where change occurred, more species have moved to lower threat categories than to higher categories, because of improved knowledge of species and their distributions, rather than a decrease in extinction risk. However, some cases of genuine deterioration in conservation status were also identified. Palms in Madagascar are primarily threatened by habitat loss due to agriculture and biological resource use through direct exploitation or collateral damage. The recent extension of Madagascar’s protected area network is highly beneficial for palms, substantially increasing the number of threatened species populations included within reserves. Notably, three of the eight most important protected areas for palms are newly designated. However, 28 threatened and data deficient species are not protected by the expanded network, including some Critically Endangered species. Moreover, many species occurring in protected areas are still threatened, indicating that threatening processes persist even in reserves. Definitive implementation of the new protected areas combined

  6. Comparative study of the Aristotle Comprehensive Complexity and the Risk Adjustment in Congenital Heart Surgery scores.

    PubMed

    Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

    2011-09-01

    The Aristotle Comprehensive Complexity (ACC) and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) scores have been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. Previous studies found RACHS-1 to be a better predictor of outcome than the Aristotle Basic Complexity score. We compared the ability to predict operative mortality and morbidity between ACC, the latest update of the Aristotle method and RACHS-1. Morbidity was assessed by length of intensive care unit stay. We retrospectively enrolled patients undergoing congenital heart surgery. We modeled each score as a continuous variable, mortality as a binary variable, and length of stay as a censored variable. We compared performance between mortality and morbidity models using likelihood ratio tests for nested models and paired concordance statistics. Among all 1,384 patients enrolled, 30-day mortality rate was 3.5% and median length of intensive care unit stay was 3 days. Both scores strongly related to mortality, but ACC made better prediction than RACHS-1; c-indexes 0.87 (0.84, 0.91) vs 0.75 (0.65, 0.82). Both scores related to overall length of stay only during the first postoperative week, but ACC made better predictions than RACHS-1; U statistic=0.22, p<0.001. No significant difference was noted after adjusting RACHS-1 models on age, prematurity, and major extracardiac abnormalities. The ACC was a better predictor of operative mortality and length of intensive care unit stay than RACHS-1. In order to achieve similar performance, regression models including RACHS-1 need to be further adjusted on age, prematurity, and major extracardiac abnormalities. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Comprehensive Red List assessment reveals exceptionally high extinction risk to Madagascar palms.

    PubMed

    Rakotoarinivo, Mijoro; Dransfield, John; Bachman, Steven P; Moat, Justin; Baker, William J

    2014-01-01

    The establishment of baseline IUCN Red List assessments for plants is a crucial step in conservation planning. Nowhere is this more important than in biodiversity hotspots that are subject to significant anthropogenic pressures, such as Madagascar. Here, all Madagascar palm species are assessed using the IUCN Red List categories and criteria, version 3.1. Our results indicate that 83% of the 192 endemic species are threatened, nearly four times the proportion estimated for plants globally and exceeding estimates for all other comprehensively evaluated plant groups in Madagascar. Compared with a previous assessment in 1995, the number of Endangered and Critically Endangered species has substantially increased, due to the discovery of 28 new species since 1995, most of which are highly threatened. The conservation status of most species included in both the 1995 and the current assessments has not changed. Where change occurred, more species have moved to lower threat categories than to higher categories, because of improved knowledge of species and their distributions, rather than a decrease in extinction risk. However, some cases of genuine deterioration in conservation status were also identified. Palms in Madagascar are primarily threatened by habitat loss due to agriculture and biological resource use through direct exploitation or collateral damage. The recent extension of Madagascar's protected area network is highly beneficial for palms, substantially increasing the number of threatened species populations included within reserves. Notably, three of the eight most important protected areas for palms are newly designated. However, 28 threatened and data deficient species are not protected by the expanded network, including some Critically Endangered species. Moreover, many species occurring in protected areas are still threatened, indicating that threatening processes persist even in reserves. Definitive implementation of the new protected areas combined with

  8. Emerging health risks associated with modern agriculture practices: a comprehensive study in India.

    PubMed

    Sarkar, Atanu; Aronson, Kristan J; Patil, Shantagouda; Hugar, Lingappa B; vanLoon, Gary W

    2012-05-01

    In order to enhance food production, India has adopted modern agriculture practices and achieved noteworthy success. This achievement was essentially the result of a paradigm shift in agriculture that included high inputs of agrochemicals, water, and widespread practice of monoculture, as well as bureaucratic changes that promoted these changes. There are very few comprehensive analyses of potential adverse health outcomes that may be related to these changes. The objective of this study is to identify health risks associated with modern agricultural practices in the southern Indian state of Karnataka. This study aims to compare high-input and low-input agricultural practices and the consequences for health of people in these communities. The fieldwork was conducted from May to August, 2009 and included a survey carried out in six villages. Data were collected by in-depth personal interviews among 240 households and key informants, field observations, laboratory analyses, and data from secondary sources. The study identified four major visible impacts: occupational hazards, vector borne diseases, changing nutritional status, and inequity in development. In the high-input area, mechanization has resulted in more occurrences of serious accidents and injuries. Ecological changes due to rice cultivation in this area have further augmented mosquito breeding, and there has been a surge in the incidence of Japanese encephalitis and malaria. The traditional coarse cereals (complex carbohydrates, high protein) have been replaced by mill-polished rice (simple carbohydrate, low protein). The prevalence of overweight (BMI>25) has emerged as a new public health challenge, and this is most evident in large-landholding households, especially in the high-input agriculture areas. In all agro-ecological areas, it was observed that women faced a greater risk of both extremes of under-nutrition and being overweight. Output-driven and market-oriented modern agricultural practices have

  9. Comprehensively identifying and characterizing the missing gene sequences in human reference genome with integrated analytic approaches.

    PubMed

    Chen, Geng; Wang, Charles; Shi, Leming; Tong, Weida; Qu, Xiongfei; Chen, Jiwei; Yang, Jianmin; Shi, Caiping; Chen, Long; Zhou, Peiying; Lu, Bingxin; Shi, Tieliu

    2013-08-01

    The human reference genome is still incomplete and a number of gene sequences are missing from it. The approaches to uncover them, the reasons causing their absence and their functions are less explored. Here, we comprehensively identified and characterized the missing genes of human reference genome with RNA-Seq data from 16 different human tissues. By using a combined approach of genome-guided transcriptome reconstruction coupled with genome-wide comparison, we uncovered 3.78 and 2.37 Mb transcribed regions in the human genome assemblies of Celera and HuRef either missed from their homologous chromosomes of NCBI human reference genome build 37.2 or partially or entirely absent from the reference. We further identified a significant number of novel transcript contigs in each tissue from de novo transcriptome assembly that are unalignable to NCBI build 37.2 but can be aligned to at least one of the genomes from Celera, HuRef, chimpanzee, macaca or mouse. Our analyses indicate that the missing genes could result from genome misassembly, transposition, copy number variation, translocation and other structural variations. Moreover, our results further suggest that a large portion of these missing genes are conserved between human and other mammals, implying their important biological functions. Totally, 1,233 functional protein domains were detected in these missing genes. Collectively, our study not only provides approaches for uncovering the missing genes of a genome, but also proposes the potential reasons causing genes missed from the genome and highlights the importance of uncovering the missing genes of incomplete genomes.

  10. A comprehensive catalogue of somatic mutations from a human cancer genome

    PubMed Central

    Pleasance, Erin D.; Cheetham, R. Keira; Stephens, Philip J.; McBride, David J.; Humphray, Sean J.; Greenman, Chris D.; Varela, Ignacio; Lin, Meng-Lay; Ordóñez, Gonzalo R.; Bignell, Graham R.; Ye, Kai; Alipaz, Julie; Bauer, Markus J.; Beare, David; Butler, Adam; Carter, Richard J.; Chen, Lina; Cox, Anthony J.; Edkins, Sarah; Kokko-Gonzales, Paula I.; Gormley, Niall A.; Grocock, Russell J.; Haudenschild, Christian D.; Hims, Matthew M.; James, Terena; Jia, Mingming; Kingsbury, Zoya; Leroy, Catherine; Marshall, John; Menzies, Andrew; Mudie, Laura J.; Ning, Zemin; Royce, Tom; Schulz-Trieglaff, Ole B.; Spiridou, Anastassia; Stebbings, Lucy A.; Szajkowski, Lukasz; Teague, Jon; Williamson, David; Chin, Lynda; Ross, Mark T.; Campbell, Peter J.; Bentley, David R.; Futreal, P. Andrew; Stratton, Michael R.

    2011-01-01

    All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic. PMID:20016485

  11. Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

    ERIC Educational Resources Information Center

    Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

    2004-01-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

  12. Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

    ERIC Educational Resources Information Center

    Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

    2004-01-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

  13. TOXICOPROTEOMICS AND ITS APPLICATION TO HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    Humans are exposed to a variety of environmental toxicants, and this together with a large number of interacting factors can contribute to an individual's risk for health. To understand the toxic mechanisms and/or modes of action for human health risk assessment, molecular charac...

  14. INCORPORATING HUMAN INTERINDIVIDUAL BIOTRANSFORMATION VARIANCE IN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accom...

  15. Incorporating Human Interindividual Biotransformation Variance in Health Risk Assessment

    EPA Science Inventory

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accom...

  16. Training Manual for Human Service Risk Managers. Final Report.

    ERIC Educational Resources Information Center

    Davis, Frank W.; And Others

    This manual is designed to educate human service agency management personnel involved in transportation about basic risk management principles and insurance issues. Chapter I illustrates the liability factors that create the insurance and risk management needs. Both legal and humanitarian obligations of human service agencies involved in…

  17. Incorporating Human Interindividual Biotransformation Variance in Health Risk Assessment

    EPA Science Inventory

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accom...

  18. TOXICOPROTEOMICS AND ITS APPLICATION TO HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    Humans are exposed to a variety of environmental toxicants, and this together with a large number of interacting factors can contribute to an individual's risk for health. To understand the toxic mechanisms and/or modes of action for human health risk assessment, molecular charac...

  19. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    PubMed Central

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  20. Human health risks associated with asbestos abatement

    SciTech Connect

    Chrostowski, P.C.; Foster, S.A.; Anderson, E.L. )

    1991-09-01

    Upperbound lifetime excess cancer risks were calculated for activities associated with asbestos abatement using a risk assessment framework developed for EPA's Superfund program. It was found that removals were associated with cancer risks to workers which were often greater than the commonly accepted cancer risk of 1 {times} 10(-6), although lower than occupational exposure limits associated with risks of 1 {times} 10(-3). Removals had little effect in reducing risk to school populations. Risks to teachers and students in school buildings containing asbestos were approximately the same as risks associated with exposure to ambient asbestos by the general public and were below the levels typically of concern to regulatory agencies. During abatement, however, there were increased risks to both workers and nearby individuals. Careless, everyday building maintenance generated the greatest risk to workers followed by removals and encapsulation. If asbestos abatement was judged by the risk criteria applied to EPA's Superfund program, the no-action alternative would likely be selected in preference to removal in a majority of cases. These conclusions should only be interpreted within the context of an overall asbestos risk management program, which includes consideration of specific fiber types and sizes, sampling and analytical limitations, physical condition of asbestos-containing material, episodic peak exposures, and the number of people potentially exposed.

  1. Design and rationale of the comprehensive evaluation of risk factors in older patients with AMI (SILVER-AMI) study.

    PubMed

    Dodson, John A; Geda, Mary; Krumholz, Harlan M; Lorenze, Nancy; Murphy, Terrence E; Allore, Heather G; Charpentier, Peter; Tsang, Sui W; Acampora, Denise; Tinetti, Mary E; Gill, Thomas M; Chaudhry, Sarwat I

    2014-11-05

    While older adults (age 75 and over) represent a large and growing proportion of patients with acute myocardial infarction (AMI), they have traditionally been under-represented in cardiovascular studies. Although chronological age confers an increased risk for adverse outcomes, our current understanding of the heterogeneity of this risk is limited. The Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study was designed to address this gap in knowledge by evaluating risk factors (including geriatric impairments, such as muscle weakness and cognitive impairments) for hospital readmission, mortality, and health status decline among older adults hospitalized for AMI. SILVER-AMI is a prospective cohort study that is enrolling 3000 older adults hospitalized for AMI from a recruitment network of approximately 70 community and academic hospitals across the United States. Participants undergo a comprehensive in-hospital assessment that includes clinical characteristics, geriatric impairments, and health status measures. Detailed medical record abstraction complements the assessment with diagnostic study results, in-hospital procedures, and medications. Participants are subsequently followed for six months to determine hospital readmission, mortality, and health status decline. Multivariable regression will be used to develop risk models for these three outcomes. SILVER-AMI will fill critical gaps in our understanding of AMI in older patients. By incorporating geriatric impairments into our understanding of post-AMI outcomes, we aim to create a more personalized assessment of risk and identify potential targets for interventions. NCT01755052 .

  2. Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease.

    PubMed

    Cifani, Paolo; Kentsis, Alex

    2017-01-01

    Given superior analytical features, MS proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern MS enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy MS in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and posttranslational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and MS proteomics are poised for immediate translation into improved diagnostic strategies for pediatric and adult diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Human health risk assessment of 2-mercaptobenzothiazole in drinking water.

    PubMed

    Whittaker, Margaret H; Gebhart, Ann Marie; Miller, Thea Clipson; Hammer, Frank

    2004-09-01

    2-Mercaptobenzothiazole (MBT) is used as a vulcanization accelerator in rubber products that come into contact with potable drinking water. When such products are evaluated for contact with potable water and submitted for ANSI/NSF Standard 61 certification, any chemical extracting from these products must be below an appropriate action level of exposure. As defined by Standard 61, a total allowable concentration (TAC) is the maximum concentration of a nonregulated contaminant allowed in a public drinking water supply, and the single product allowable concentration (SPAC) is 10% of the TAC. Currently, MBT has a TAC of 40 microg/L and a SPAC of 4 microg/L. A comprehensive health effects evaluation of MBT was performed to determine whether these action levels should be revised. Epidemiological investigations indicate that workers occupationally exposed to MBT have an increased risk of death from bladder cancer. Genotoxicity investigations in bacterial and mammalian test systems provide some evidence indicating that MBT has the potential to induce mutations and chromosomal aberrations. Toxicity studies in rats and mice chronically exposed to MBT identified increases in various tumours, such as adrenal gland tumours, pituitary gland tumours, liver tumours and renal pelvis tumours. The biological significance of most of these tumours is questionable due to a variety of factors, such as a lack of dose-response between tumour incidence and dose, and the effect of test article vehicle (corn oil) upon tumour rates. Potential human health effects of exposure to MBT can be predicted from an NTP 2-year cancer study in rats, as well as epidemiological investigations in occupationally exposed workers. A comprehensive review of the epidemiological and toxicological dataset for MBT indicates that the induction of renal pelvis transitional cell tumours is the most sensitive and relevant health effects endpoint upon which to base a revised TAC and SPAC. A multistage model was used to

  4. circRNADb: A comprehensive database for human circular RNAs with protein-coding annotations

    PubMed Central

    Chen, Xiaoping; Han, Ping; Zhou, Tao; Guo, Xuejiang; Song, Xiaofeng; Li, Yan

    2016-01-01

    It has been known that circular RNAs are widely expressed in human tissues and cells, and play important regulatory roles in physiological or pathological processes. However, there is lack of comprehensively annotated human circular RNAs database. In this study we established a circRNA database, named as circRNADb, containing 32,914 human exonic circRNAs carefully selected from diversified sources. The detailed information of the circRNA, including genomic information, exon splicing, genome sequence, internal ribosome entry site (IRES), open reading frame (ORF) and references were provided in circRNADb. In addition, circRNAs were found to be able to encode proteins, which have not been reported in any species. 16328 circRNAs were annotated to have ORF longer than 100 amino acids, of which 7170 have IRES elements. 46 circRNAs from 37 genes were found to have their corresponding proteins expressed according mass spectrometry. The database provides the function of data search, browse, download, submit and feedback for the user to study particular circular RNA of interest and update the database continually. circRNADb will be built to be a biological information platform for circRNA molecules and related biological functions in the future. The database can be freely available through the web server at http://reprod.njmu.edu.cn/circrnadb. PMID:27725737

  5. CD34 expression in human hair follicles and tricholemmoma: a comprehensive study.

    PubMed

    Misago, Noriyuki; Toda, Shuji; Narisawa, Yutaka

    2011-08-01

    There has recently been controversy regarding whether clone My10 is superior to clone QBEND-10 for labeling cells of tricholemmal lineage. Moreover, there have been no previous reports on the CD34 expression in human vellus hair follicles. We performed a comprehensive study of the CD34 expression in human terminal and vellus hair follicles and in 10 tricholemmomas using both the QBEND-10 and the My10 clones. We also performed two different procedures of immunostaining, which included the using of the standard avidin-biotin-peroxidase (ABC) complex system and the Envision system. The most sensitive marker of CD34 for normal human hair follicles and tricholemmomas is QBEND-10 using the ABC system. The degree and strength of the CD34 positive staining mainly depended on the method being used (whether it was the ABC system or the Envision system) rather than the clone. CD34 staining was rarely (20-30%) seen in the anagen and catagen vellus hair follicles, and could only be seen by the QBEND-10 clone using the ABC system. CD34 expression in the tricholemmomas represented either a diffuse or peripheral pattern. CD34 may not be a tricholemmal lineage-specific antigen, but may be related to certain functions of the cells. Copyright © 2011 John Wiley & Sons A/S.

  6. Risk Assessment: Perchloroethylene Dry Cleaners Refined Human Health Risk Characterization

    EPA Pesticide Factsheets

    This November 2005 memo and appendices describe the methods by which EPA conducted its refined risk assessment of the Major Source and Area Source facilities within the perchloroethylene (perc) dry cleaners source category.

  7. Impact of comprehensive cardiovascular risk reduction programme on risk factor clustering associated with elevated blood pressure in an Indian industrial population.

    PubMed

    Jeemon, Panniyammakal; Prabhakaran, Dorairaj; Goenka, Shifalika; Ramakrishnan, Lakshmy; Padmanabhan, Sandosh; Huffman, Mark; Joshi, Prashant; Sivasankaran, Sivasubramonian; Mohan, B V M; Ahmed, F; Ramanathan, Meera; Ahuja, R; Sinha, Nakul; Thankappan, K R; Reddy, K S

    2012-04-01

    Cardiovascular risk factors clustering associated with blood pressure (BP) has not been studied in the Indian population. This study was aimed at assessing the clustering effect of cardiovascular risk factors with suboptimal BP in Indian population as also the impact of risk reduction interventions. Data from 10543 individuals collected in a nation-wide surveillance programme in India were analysed. The burden of risk factors clustering with blood pressure and coronary heart disease (CHD) was assessed. The impact of a risk reduction programmme on risk factors clustering was prospectively studied in a sub-group. Mean age of participants was 40.9 ± 11.0 yr. A significant linear increase in number of risk factors with increasing blood pressure, irrespective of stratifying using different risk factor thresholds was observed. While hypertension occurred in isolation in 2.6 per cent of the total population, co-existence of hypertension and >3 risk factors was observed in 12.3 per cent population. A comprehensive risk reduction programme significantly reduced the mean number of additional risk factors in the intervention population across the blood pressure groups, while it continued to be high in the control arm without interventions (both within group and between group P<0.001). The proportion of 'low risk phenotype' increased from 13.4 to 19.9 per cent in the intervention population and it was decreased from 27.8 to 10.6 per cent in the control population (P<0.001). The proportion of individuals with hypertension and three more risk factors decreased from 10.6 to 4.7 per cent in the intervention arm while it was increased from 13.3 to 17.8 per cent in the control arm (P<0.001). Our findings showed that cardiovascular risk factors clustered together with elevated blood pressure and a risk reduction programme significantly reduced the risk factors burden.

  8. Impact of comprehensive cardiovascular risk reduction programme on risk factor clustering associated with elevated blood pressure in an Indian industrial population

    PubMed Central

    Jeemon, Panniyammakal; Prabhakaran, Dorairaj; Goenka, Shifalika; Ramakrishnan, Lakshmy; Padmanabhan, Sandosh; Huffman, Mark; Joshi, Prashant; Sivasankaran, Sivasubramonian; Mohan, B.V.M.; Ahmed, F.; Ramanathan, Meera; Ahuja, R.; Sinha, Nakul; Thankappan, K.R.; Reddy, K.S.

    2012-01-01

    Background & objectives: Cardiovascular risk factors clustering associated with blood pressure (BP) has not been studied in the Indian population. This study was aimed at assessing the clustering effect of cardiovascular risk factors with suboptimal BP in Indian population as also the impact of risk reduction interventions. Methods: Data from 10543 individuals collected in a nation-wide surveillance programme in India were analysed. The burden of risk factors clustering with blood pressure and coronary heart disease (CHD) was assessed. The impact of a risk reduction programmme on risk factors clustering was prospectively studied in a sub-group. Results: Mean age of participants was 40.9 ± 11.0 yr. A significant linear increase in number of risk factors with increasing blood pressure, irrespective of stratifying using different risk factor thresholds was observed. While hypertension occurred in isolation in 2.6 per cent of the total population, co-existence of hypertension and >3 risk factors was observed in 12.3 per cent population. A comprehensive risk reduction programme significantly reduced the mean number of additional risk factors in the intervention population across the blood pressure groups, while it continued to be high in the control arm without interventions (both within group and between group P<0.001). The proportion of ‘low risk phenotype’ increased from 13.4 to 19.9 per cent in the intervention population and it was decreased from 27.8 to 10.6 per cent in the control population (P<0.001). The proportion of individuals with hypertension and three more risk factors decreased from 10.6 to 4.7 per cent in the intervention arm while it was increased from 13.3 to 17.8 per cent in the control arm (P<0.001). Interpretation & conclusions: Our findings showed that cardiovascular risk factors clustered together with elevated blood pressure and a risk reduction programme significantly reduced the risk factors burden. PMID:22664495

  9. Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update

    PubMed Central

    2012-01-01

    Background Human cerebral spinal fluid (CSF) is known to be a rich source of small molecule biomarkers for neurological and neurodegenerative diseases. In 2007, we conducted a comprehensive metabolomic study and performed a detailed literature review on metabolites that could be detected (via metabolomics or other techniques) in CSF. A total of 308 detectable metabolites were identified, of which only 23% were shown to be routinely identifiable or quantifiable with the metabolomics technologies available at that time. The continuing advancement in analytical technologies along with the growing interest in CSF metabolomics has led us to re-visit the human CSF metabolome and to re-assess both its size and the level of coverage than can be achieved with today's technologies. Methods We used five analytical platforms, including nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), direct flow injection-mass spectrometry (DFI-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS) to perform quantitative metabolomics on multiple human CSF samples. This experimental work was complemented with an extensive literature review to acquire additional information on reported CSF compounds, their concentrations and their disease associations. Results NMR, GC-MS and LC-MS methods allowed the identification and quantification of 70 CSF metabolites (as previously reported). DFI-MS/MS allowed the quantification of 78 metabolites (6 acylcarnitines, 13 amino acids, hexose, 42 phosphatidylcholines, 2 lyso-phosphatidylcholines and 14 sphingolipids), while ICP-MS provided quantitative results for 33 metal ions in CSF. Literature analysis led to the identification of 57 more metabolites. In total, 476 compounds have now been confirmed to exist in human CSF. Conclusions The use of improved metabolomic and other analytical techniques has led to a 54% increase in the known size of the human CSF metabolome

  10. Risk perception, risk evaluation and human values: Cognitive bases acceptability of a radioactive waste repository

    NASA Astrophysics Data System (ADS)

    Earle, T. C.; Lindell, M. K.; Rankin, W. L.; Nealey, S. M.

    1981-07-01

    Public acceptance of radioactive waste management alternatives depends in part on public perception of the associated risks. Three aspects of those perceived risks were explored: (1) synthetic measures of risk perception based on judgments of probability and consequences; (2) acceptability of hypothetical radioactive waste policies; and (3) effects of human values on risk perception. Both the work on synthetic measures of risk perception and on the acceptability of hypothetical policies included investigations of three categories of risk: short term public risk (affecting persons living when the wastes are created), long term public risk (affecting persons living after the time the wastes were created), and occupational risk (affecting persons working with the radioactive wastes). The human values work related to public risk perception in general, across categories of persons affected. Respondents were selected according to a purposive sampling strategy.

  11. Risk perception, risk evaluation and human values: cognitive bases of acceptability of a radioactive waste repository

    SciTech Connect

    Earle, T.C.; Lindell, M.K.; Rankin, W.L.

    1981-07-01

    Public acceptance of radioactive waste management alternatives depends in part on public perception of the associated risks. Three aspects of those perceived risks were explored in this study: (1) synthetic measures of risk perception based on judgments of probability and consequences; (2) acceptability of hypothetical radioactive waste policies, and (3) effects of human values on risk perception. Both the work on synthetic measures of risk perception and on the acceptability of hypothetical policies included investigations of three categories of risk: (1) Short-term public risk (affecting persons living when the wastes are created), (2) Long-term public risk (affecting persons living after the time the wastes were created), and (3) Occupational risk (affecting persons working with the radioactive wastes). The human values work related to public risk perception in general, across categories of persons affected. Respondents were selected according to a purposive sampling strategy.

  12. Humans vs Hardware: The Unique World of NASA Human System Risk Assessment

    NASA Technical Reports Server (NTRS)

    Anton, W.; Havenhill, M.; Overton, Eric

    2016-01-01

    Understanding spaceflight risks to crew health and performance is a crucial aspect of preparing for exploration missions in the future. The research activities of the Human Research Program (HRP) provide substantial evidence to support most risk reduction work. The Human System Risk Board (HSRB), acting on behalf of the Office of Chief Health and Medical Officer (OCHMO), assesses these risks and assigns likelihood and consequence ratings to track progress. Unfortunately, many traditional approaches in risk assessment such as those used in the engineering aspects of spaceflight are difficult to apply to human system risks. This presentation discusses the unique aspects of risk assessment from the human system risk perspective and how these limitations are accommodated and addressed in order to ensure that reasonable inputs are provided to support the OCHMO's overall risk posture for manned exploration missions.

  13. Development and Implementation of a Comprehensive Risk Management Program at the USAF Academy Hospital, USAF Academy, Colorado

    DTIC Science & Technology

    1980-04-01

    Health Ca Admin/HSHA-IE, MO wL ADMRSS (OCy. Stemf. end ZIP Caft 7b. ADDRESS (City. State. dZI oct FT Sam Houston, TX 78234-6100 .’a" NAME O; FUNO.Nt...Contmnue on rwvwrse d necesjry and idenfy by b•ock number) 4ELO GROUP SUB.GROUP HEALTH CARE; CCANPREHE.NSIVE RISK 1.1NAG&E’ ,- I J. ABSTRACT...Comprehensive Risk Management program to effectively reduce malpractice claims against "an Air Force health care facility. The study objectives were to gather

  14. Clean Slate transportation and human health risk assessment

    SciTech Connect

    1997-02-01

    Public concern regarding activities involving radioactive material generally focuses on the human health risk associated with exposure to ionizing radiation. This report describes the results of a risk analysis conducted to evaluate risk for excavation, handling, and transport of soil contaminated with transuranics at the Clean Slate sites. Transportation risks were estimated for public transport routes from the Tonopah Test Range (TTR) to the Envirocore disposal facility or to the Area 3 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS) for both radiological risk and risk due to traffic accidents. Human health risks were evaluated for occupational and radiation-related health effects to workers. This report was generated to respond to this public concern, to provide an evaluation of the risk, and to assess feasibility of transport of the contaminated soil for disposal.

  15. Human risk from thermotolerant Campylobacter on broiler meat in Denmark.

    PubMed

    Boysen, Louise; Nauta, Maarten; Duarte, Ana Sofia Ribeiro; Rosenquist, Hanne

    2013-03-15

    This paper describes a new approach by which changes over time in the relative risk of human campylobacteriosis from broiler meat are evaluated through quantitative microbiological risk assessment modelling. Danish surveillance data collected at retail from 2001 to 2010 on numbers of thermotolerant Campylobacter spp. on Danish produced and imported chilled and frozen broiler meat were the basis for the investigation. The aim was to explore if the risk from the different meat categories had changed over time as a consequence of implemented intervention strategies. The results showed a slight decrease from 2005 to 2008 in the human risk from Danish produced broiler meat, and a decrease from 2005 to 2010 in the risk from imported chilled meat. This risk reduction coincides with control measures implemented to reduce Campylobacter in Danish and imported chilled broiler meat. The human risk of campylobacteriosis from Danish frozen meat increased but remained lower compared to chilled meat. In total, the relative risk from broiler meat available for sale in Denmark increased from 2001 to 2005 after which the risk decreased to a level similar to the period 2001-2002. The use of QMRA in the evaluation of intervention strategies based on monitoring data provided an added value, compared to the traditional approach of only using changes in prevalence. The estimated human health risk is a function of prevalence and the distribution of concentrations, and therefore takes best usage of the available data, while providing the most relevant outcome for food safety risk managers.

  16. Human activities change marine ecosystems by altering predation risk.

    PubMed

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises.

  17. A 21st Century Roadmap for Human Health Risk Assessment ...

    EPA Pesticide Factsheets

    For decades human health risk assessment has depended primarily on animal testing to predict adverse effects in humans, but that paradigm has come under question because of calls for more accurate information, less use of animals, and more efficient use of resources. Moreover, the disproportionate use of hazard information has overshadowed the important role of exposure science in determinations of human safety. In addition, major risk assessments lack the clarity and transparency that hinder an understanding of the analysis and communication of key safety messages. To help answer these challenges, the HESI-managed RISK21 project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment. RISK21 involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. RISK21 developed a tiered approach that is problem formulation-based, makes maximum use of prior knowledge, and is led by exposure science to produce a highly transparent and flexible visualization of and approach to assessing human safety and risk. The general principles underlying the RISK21 approach as well as an overview of the RISK21 Roadmap are presented here. This paper will be followed by a series of publications that will articulate the details that comprise this systematic approach. The purpose of this manuscript is to provide an overview

  18. Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts

    PubMed Central

    Ishii, Genichiro; Aoyagi, Kazuhiko; Sasaki, Hiroki; Ochiai, Atsushi

    2015-01-01

    Background Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body. Methods Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup. Results In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling. Conclusions GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract. PMID:26046848

  19. A Comprehensive Analysis on Wearable Acceleration Sensors in Human Activity Recognition.

    PubMed

    Janidarmian, Majid; Roshan Fekr, Atena; Radecka, Katarzyna; Zilic, Zeljko

    2017-03-07

    Sensor-based motion recognition integrates the emerging area of wearable sensors with novel machine learning techniques to make sense of low-level sensor data and provide rich contextual information in a real-life application. Although Human Activity Recognition (HAR) problem has been drawing the attention of researchers, it is still a subject of much debate due to the diverse nature of human activities and their tracking methods. Finding the best predictive model in this problem while considering different sources of heterogeneities can be very difficult to analyze theoretically, which stresses the need of an experimental study. Therefore, in this paper, we first create the most complete dataset, focusing on accelerometer sensors, with various sources of heterogeneities. We then conduct an extensive analysis on feature representations and classification techniques (the most comprehensive comparison yet with 293 classifiers) for activity recognition. Principal component analysis is applied to reduce the feature vector dimension while keeping essential information. The average classification accuracy of eight sensor positions is reported to be 96.44% ± 1.62% with 10-fold evaluation, whereas accuracy of 79.92% ± 9.68% is reached in the subject-independent evaluation. This study presents significant evidence that we can build predictive models for HAR problem under more realistic conditions, and still achieve highly accurate results.

  20. Comprehensive Survey of Intestinal Microbiota Changes in Offspring of Human Microbiota-Associated Mice

    PubMed Central

    von Klitzing, Eliane; Öz, Fulya; Ekmekciu, Ira; Escher, Ulrike; Bereswill, Stefan; Heimesaat, Markus M.

    2017-01-01

    Secondary abiotic mice generated by broad-spectrum antibiotic treatment provide a valuable tool for association studies with microbiota derived from different vertebrate hosts. We here generated human microbiota-associated (hma) mice by human fecal microbiota transplantation of secondary abiotic mice and performed a comprehensive survey of the intestinal microbiota dynamics in offspring of hma mice over 18 weeks following weaning as compared to their mothers applying both cultural and molecular methods. Mice were maintained under standard hygienic conditions with open cages, handled under aseptic conditions, and fed autoclaved chow and water. Within 1 week post weaning, fecal loads of commensal enterobacteria and enterococci had decreased, whereas obligate anaerobic bacteria such as Bacteroides/Prevotella species and clostridia were stably colonizing the intestines of hma offspring at high loads. Lactobacilli numbers were successively increasing until 18 weeks post weaning in both hma offspring and mothers, whereas by then, bifidobacteria were virtually undetectable in the former only. Interestingly, fecal lactobacilli and bifidobacteria were higher in mothers as compared to their offspring at 5 and 18 weeks post weaning. We conclude that the intestinal microbiota composition changes in offspring of hma mice, but also their mothers over time particularly affecting aerobic and microaerobic species. PMID:28386472

  1. RAID: a comprehensive resource for human RNA-associated (RNA-RNA/RNA-protein) interaction.

    PubMed

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-07-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA-RNA/RNA-protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA-RNA interactions and 1619 RNA-protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA-RNA/RNA-protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA-RNA/RNA-protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. © 2014 Zhang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  2. Comprehensive reconstruction and visualization of non-coding regulatory networks in human.

    PubMed

    Bonnici, Vincenzo; Russo, Francesco; Bombieri, Nicola; Pulvirenti, Alfredo; Giugno, Rosalba

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape.

  3. Comprehensive Gene Expression Analysis of Human Embryonic Stem Cells during Differentiation into Neural Cells

    PubMed Central

    Fathi, Ali; Hatami, Maryam; Hajihosseini, Vahid; Fattahi, Faranak; Kiani, Sahar; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2011-01-01

    Global gene expression analysis of human embryonic stem cells (hESCs) that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcripteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm, and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. An interaction network analysis revealed that the TGFβ family of genes, including LEFTY1, ID1 and ID2, are possible key players in the proliferation and maintenance of neural ectoderm. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation. PMID:21829537

  4. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.

    PubMed

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. A Comprehensive Analysis on Wearable Acceleration Sensors in Human Activity Recognition

    PubMed Central

    Janidarmian, Majid; Roshan Fekr, Atena; Radecka, Katarzyna; Zilic, Zeljko

    2017-01-01

    Sensor-based motion recognition integrates the emerging area of wearable sensors with novel machine learning techniques to make sense of low-level sensor data and provide rich contextual information in a real-life application. Although Human Activity Recognition (HAR) problem has been drawing the attention of researchers, it is still a subject of much debate due to the diverse nature of human activities and their tracking methods. Finding the best predictive model in this problem while considering different sources of heterogeneities can be very difficult to analyze theoretically, which stresses the need of an experimental study. Therefore, in this paper, we first create the most complete dataset, focusing on accelerometer sensors, with various sources of heterogeneities. We then conduct an extensive analysis on feature representations and classification techniques (the most comprehensive comparison yet with 293 classifiers) for activity recognition. Principal component analysis is applied to reduce the feature vector dimension while keeping essential information. The average classification accuracy of eight sensor positions is reported to be 96.44% ± 1.62% with 10-fold evaluation, whereas accuracy of 79.92% ± 9.68% is reached in the subject-independent evaluation. This study presents significant evidence that we can build predictive models for HAR problem under more realistic conditions, and still achieve highly accurate results. PMID:28272362

  6. A comprehensive experimental study on material properties of human brain tissue.

    PubMed

    Jin, Xin; Zhu, Feng; Mao, Haojie; Shen, Ming; Yang, King H

    2013-11-15

    A comprehensive study on the biomechanical response of human brain tissue is necessary to investigate traumatic brain injury mechanisms. Published brain material property studies have been mostly performed under a specific type of loading, which is insufficient to develop accurate brain tissue constitutive equations. In addition, inconsistent or contradictory data in the literature made it impossible for computational model developers to create a single brain material model that can fit most, if not all, experimental results. In the current study, a total of 240 brain tissue specimens were tested under tension (n=72), compression (n=72), and shear (n=96) loading modes at varying strain rates. Gray-white matter difference, regional difference, and directional difference within white matter were also investigated. Stress-strain relationships of human brain tissue were obtained up to 50% of engineering strain. Strain rate dependency was observed under all three loading modes. White matter was stiffer than gray matter in compression and shear. Corona radiata was found to be stiffer than cortex, thalamus, and corpus callosum in tension and compression. Directional dependency of white matter was observed under shear loading.

  7. Comprehensive Survey of Intestinal Microbiota Changes in Offspring of Human Microbiota-Associated Mice.

    PubMed

    von Klitzing, Eliane; Öz, Fulya; Ekmekciu, Ira; Escher, Ulrike; Bereswill, Stefan; Heimesaat, Markus M

    2017-03-01

    Secondary abiotic mice generated by broad-spectrum antibiotic treatment provide a valuable tool for association studies with microbiota derived from different vertebrate hosts. We here generated human microbiota-associated (hma) mice by human fecal microbiota transplantation of secondary abiotic mice and performed a comprehensive survey of the intestinal microbiota dynamics in offspring of hma mice over 18 weeks following weaning as compared to their mothers applying both cultural and molecular methods. Mice were maintained under standard hygienic conditions with open cages, handled under aseptic conditions, and fed autoclaved chow and water. Within 1 week post weaning, fecal loads of commensal enterobacteria and enterococci had decreased, whereas obligate anaerobic bacteria such as Bacteroides/Prevotella species and clostridia were stably colonizing the intestines of hma offspring at high loads. Lactobacilli numbers were successively increasing until 18 weeks post weaning in both hma offspring and mothers, whereas by then, bifidobacteria were virtually undetectable in the former only. Interestingly, fecal lactobacilli and bifidobacteria were higher in mothers as compared to their offspring at 5 and 18 weeks post weaning. We conclude that the intestinal microbiota composition changes in offspring of hma mice, but also their mothers over time particularly affecting aerobic and microaerobic species.

  8. A Comprehensive Review of Apples and Apple Components and Their Relationship to Human Health12

    PubMed Central

    Hyson, Dianne A.

    2011-01-01

    There has been an increasing appreciation and understanding of the link between dietary fruit and vegetable intake and improved health in humans. The widespread and growing intake of apples and apple juice/products and their rich phytochemical profile suggest their important potential to affect the health of the populations consuming them. This review summarizes current clinical, in vitro, and in vivo data and builds upon earlier published reports that apple may reduce the risk of chronic disease by various mechanisms, including antioxidant, antiproliferative, and cell signaling effects. Exposure to apples and apple products has been associated with beneficial effects on risk, markers, and etiology of cancer, cardiovascular disease, asthma, and Alzheimer’s disease. Recent work suggests that these products may also be associated with improved outcomes related to cognitive decline of normal aging, diabetes, weight management, bone health, pulmonary function, and gastrointestinal protection. PMID:22332082

  9. Analytic concepts for assessing risk as applied to human space flight

    SciTech Connect

    Garrick, B.J.

    1997-04-30

    Quantitative risk assessment (QRA) principles provide an effective framework for quantifying individual elements of risk, including the risk to astronauts and spacecraft of the radiation environment of space flight. The concept of QRA is based on a structured set of scenarios that could lead to different damage states initiated by either hardware failure, human error, or external events. In the context of a spacecraft risk assessment, radiation may be considered as an external event and analyzed in the same basic way as any other contributor to risk. It is possible to turn up the microscope on any particular contributor to risk and ask more detailed questions than might be necessary to simply assess safety. The methods of QRA allow for as much fine structure in the analysis as is desired. For the purpose of developing a basis for comprehensive risk management and considering the tendency to {open_quotes}fear anything nuclear,{close_quotes} radiation risk is a prime candidate for examination beyond that necessary to answer the basic question of risk. Thus, rather than considering only the customary damage states of fatalities or loss of a spacecraft, it is suggested that the full range of damage be analyzed to quantify radiation risk. Radiation dose levels in the form of a risk curve accomplish such a result. If the risk curve is the complementary cumulative distribution function, then it answers the extended question of what is the likelihood of receiving a specific dose of radiation or greater. Such results can be converted to specific health effects as desired. Knowing the full range of the radiation risk of a space mission and the contributors to that risk provides the information necessary to take risk management actions [operational, design, scheduling of missions around solar particle events (SPE), etc.] that clearly control radiation exposure.

  10. Study on quantitative risk assessment model of the third party damage for natural gas pipelines based on fuzzy comprehensive assessment

    NASA Astrophysics Data System (ADS)

    Qiu, Zeyang; Liang, Wei; Wang, Xue; Lin, Yang; Zhang, Meng

    2017-05-01

    As an important part of national energy supply system, transmission pipelines for natural gas are possible to cause serious environmental pollution, life and property loss in case of accident. The third party damage is one of the most significant causes for natural gas pipeline system accidents, and it is very important to establish an effective quantitative risk assessment model of the third party damage for reducing the number of gas pipelines operation accidents. Against the third party damage accident has the characteristics such as diversity, complexity and uncertainty, this paper establishes a quantitative risk assessment model of the third party damage based on Analytic Hierarchy Process (AHP) and Fuzzy Comprehensive Evaluation (FCE). Firstly, risk sources of third party damage should be identified exactly, and the weight of factors could be determined via improved AHP, finally the importance of each factor is calculated by fuzzy comprehensive evaluation model. The results show that the quantitative risk assessment model is suitable for the third party damage of natural gas pipelines and improvement measures could be put forward to avoid accidents based on the importance of each factor.

  11. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review

    PubMed Central

    Jennings, Aaron

    2017-01-01

    The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human exposure

  12. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review.

    PubMed

    Li, Zijian; Jennings, Aaron

    2017-07-22

    Abstract: The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human

  13. Using ultrahigh sensitive optical microangiography to achieve comprehensive depth resolved microvasculature mapping for human retina

    NASA Astrophysics Data System (ADS)

    An, Lin; Shen, Tueng T.; Wang, Ruikang K.

    2011-10-01

    This paper presents comprehensive and depth-resolved retinal microvasculature images within human retina achieved by a newly developed ultrahigh sensitive optical microangiography (UHS-OMAG) system. Due to its high flow sensitivity, UHS-OMAG is much more sensitive to tissue motion due to the involuntary movement of the human eye and head compared to the traditional OMAG system. To mitigate these motion artifacts on final imaging results, we propose a new phase compensation algorithm in which the traditional phase-compensation algorithm is repeatedly used to efficiently minimize the motion artifacts. Comparatively, this new algorithm demonstrates at least 8 to 25 times higher motion tolerability, critical for the UHS-OMAG system to achieve retinal microvasculature images with high quality. Furthermore, the new UHS-OMAG system employs a high speed line scan CMOS camera (240 kHz A-line scan rate) to capture 500 A-lines for one B-frame at a 400 Hz frame rate. With this system, we performed a series of in vivo experiments to visualize the retinal microvasculature in humans. Two featured imaging protocols are utilized. The first is of the low lateral resolution (16 μm) and a wide field of view (4 × 3 mm2 with single scan and 7 × 8 mm2 for multiple scans), while the second is of the high lateral resolution (5 μm) and a narrow field of view (1.5 × 1.2 mm2 with single scan). The great imaging performance delivered by our system suggests that UHS-OMAG can be a promising noninvasive alternative to the current clinical retinal microvasculature imaging techniques for the diagnosis of eye diseases with significant vascular involvement, such as diabetic retinopathy and age-related macular degeneration.

  14. Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. Results We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4 × 108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA. Conclusion Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans. PMID:22846614

  15. A comprehensive mapping of the current capacity for human nutrition training in Cameroon

    PubMed Central

    Sodjinou, Roger; Lezama, Ines; Asse, Marie-Louise; Okala, Georges; Bosu, William K.; Fanou, Nadia; Mbala, Ludvine; Zagre, Noel Marie; Tchibindat, Félicité

    2016-01-01

    Background There is consensus among stakeholders in Cameroon on the need to develop and strengthen human resource capacity for nutrition. This study was conducted to provide a comprehensive mapping of the current capacity for tertiary-level human nutrition training in Cameroon. Design Participating institutions included university-level institutions offering dedicated nutrition degree programs or other programs in which nutrition courses were taught. A semi-structured questionnaire administered during in-person interviews was used to collect data on existing programs and content of training curricula. Nutrition curricula were reviewed against the following criteria: intended objectives, coverage of nutrition topics, and teaching methods. Results In total, five nutrition degree programs (four undergraduate programs and one master's program) were identified. Three additional programs were about to be launched at the time of data collection. We did not find any doctorate degree programs in nutrition. All the undergraduate programs only had little focus on public health nutrition whereas the master's program in our sample offered a good coverage of all dimensions of human nutrition including basic and applied nutrition. The predominant teaching method was didactic lecture in all the programs. We did not find any formal documentation outlining the competencies that students were expected to gain upon completion of these programs. Nutrition courses in agricultural and health schools were limited in terms of contact hours and scope. Public health nutrition was not covered in any of the health professional schools surveyed. We found no institution offering in-service nutrition training at the time of the study. Conclusions Based on our findings, we recommend that nutrition training programs in Cameroon be redesigned to make them more responsive to the public health needs of the country. PMID:26818193

  16. Human population density and extinction risk in the world's carnivores.

    PubMed

    Cardillo, Marcel; Purvis, Andy; Sechrest, Wes; Gittleman, John L; Bielby, Jon; Mace, Georgina M

    2004-07-01

    Understanding why some species are at high risk of extinction, while others remain relatively safe, is central to the development of a predictive conservation science. Recent studies have shown that a species' extinction risk may be determined by two types of factors: intrinsic biological traits and exposure to external anthropogenic threats. However, little is known about the relative and interacting effects of intrinsic and external variables on extinction risk. Using phylogenetic comparative methods, we show that extinction risk in the mammal order Carnivora is predicted more strongly by biology than exposure to high-density human populations. However, biology interacts with human population density to determine extinction risk: biological traits explain 80% of variation in risk for carnivore species with high levels of exposure to human populations, compared to 45% for carnivores generally. The results suggest that biology will become a more critical determinant of risk as human populations expand. We demonstrate how a model predicting extinction risk from biology can be combined with projected human population density to identify species likely to move most rapidly towards extinction by the year 2030. African viverrid species are particularly likely to become threatened, even though most are currently considered relatively safe. We suggest that a preemptive approach to species conservation is needed to identify and protect species that may not be threatened at present but may become so in the near future.

  17. Human Population Density and Extinction Risk in the World's Carnivores

    PubMed Central

    Purvis, Andy; Sechrest, Wes; Gittleman, John L; Bielby, Jon; Mace, Georgina M

    2004-01-01

    Understanding why some species are at high risk of extinction, while others remain relatively safe, is central to the development of a predictive conservation science. Recent studies have shown that a species' extinction risk may be determined by two types of factors: intrinsic biological traits and exposure to external anthropogenic threats. However, little is known about the relative and interacting effects of intrinsic and external variables on extinction risk. Using phylogenetic comparative methods, we show that extinction risk in the mammal order Carnivora is predicted more strongly by biology than exposure to high-density human populations. However, biology interacts with human population density to determine extinction risk: biological traits explain 80% of variation in risk for carnivore species with high levels of exposure to human populations, compared to 45% for carnivores generally. The results suggest that biology will become a more critical determinant of risk as human populations expand. We demonstrate how a model predicting extinction risk from biology can be combined with projected human population density to identify species likely to move most rapidly towards extinction by the year 2030. African viverrid species are particularly likely to become threatened, even though most are currently considered relatively safe. We suggest that a preemptive approach to species conservation is needed to identify and protect species that may not be threatened at present but may become so in the near future. PMID:15252445

  18. Reducing the Risk of Human Space Missions with INTEGRITY

    NASA Technical Reports Server (NTRS)

    Jones, Harry W.; Dillon-Merill, Robin L.; Tri, Terry O.; Henninger, Donald L.

    2003-01-01

    The INTEGRITY Program will design and operate a test bed facility to help prepare for future beyond-LEO missions. The purpose of INTEGRITY is to enable future missions by developing, testing, and demonstrating advanced human space systems. INTEGRITY will also implement and validate advanced management techniques including risk analysis and mitigation. One important way INTEGRITY will help enable future missions is by reducing their risk. A risk analysis of human space missions is important in defining the steps that INTEGRITY should take to mitigate risk. This paper describes how a Probabilistic Risk Assessment (PRA) of human space missions will help support the planning and development of INTEGRITY to maximize its benefits to future missions. PRA is a systematic methodology to decompose the system into subsystems and components, to quantify the failure risk as a function of the design elements and their corresponding probability of failure. PRA provides a quantitative estimate of the probability of failure of the system, including an assessment and display of the degree of uncertainty surrounding the probability. PRA provides a basis for understanding the impacts of decisions that affect safety, reliability, performance, and cost. Risks with both high probability and high impact are identified as top priority. The PRA of human missions beyond Earth orbit will help indicate how the risk of future human space missions can be reduced by integrating and testing systems in INTEGRITY.

  19. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies.

    PubMed

    Hopkins, Allison L; Lamm, Marnie G; Funk, Janet L; Ritenbaugh, Cheryl

    2013-03-01

    calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.

  20. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies

    PubMed Central

    Hopkins, Allison L.; Lamm, Marnie G.; Funk, Janet; Ritenbaugh, Cheryl

    2013-01-01

    calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit. PMID:23333908

  1. Postsuicide Intervention as a Prevention Tool: Developing a Comprehensive Campus Response to Suicide and Related Risk

    ERIC Educational Resources Information Center

    Cimini, M. Dolores; Rivero, Estela M.

    2013-01-01

    This chapter explores the critical role of crisis intervention and other support after a suicide has occurred as part of a comprehensive suicide prevention response within college and university campuses. The important components of postsuicide intervention campus crisis response and protocols and the identification of key stakeholders to…

  2. Exploring Dynamic Assessment as a Means of Identifying Children at Risk of Developing Comprehension Difficulties

    ERIC Educational Resources Information Center

    Elleman, Amy M.; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette

    2011-01-01

    In this study, the authors explore a newly constructed dynamic assessment (DA) intended to tap inference-making skills that they hypothesize will be predictive of future comprehension performance. The authors administered the test to 100 second-grade children using a dynamic format to consider the concurrent validity of the measure. The dynamic…

  3. Postsuicide Intervention as a Prevention Tool: Developing a Comprehensive Campus Response to Suicide and Related Risk

    ERIC Educational Resources Information Center

    Cimini, M. Dolores; Rivero, Estela M.

    2013-01-01

    This chapter explores the critical role of crisis intervention and other support after a suicide has occurred as part of a comprehensive suicide prevention response within college and university campuses. The important components of postsuicide intervention campus crisis response and protocols and the identification of key stakeholders to…

  4. Exploring Dynamic Assessment as a Means of Identifying Children at Risk of Developing Comprehension Difficulties

    ERIC Educational Resources Information Center

    Elleman, Amy M.; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette

    2011-01-01

    In this study, the authors explore a newly constructed dynamic assessment (DA) intended to tap inference-making skills that they hypothesize will be predictive of future comprehension performance. The authors administered the test to 100 second-grade children using a dynamic format to consider the concurrent validity of the measure. The dynamic…

  5. Building a Better Model: A Comprehensive Breast Cancer Risk Model Incorporating Breast Density to Stratify Risk and Apply Resources

    DTIC Science & Technology

    2014-10-01

    o Comparison of Breast Density Measurements with a Mammographic Volumetric and Area Algorithm and Magnetic resonance imaging . O Alonzo-Proulx, JG... Breast Cancer Risk Model Incorporating Breast Density To Stratify Risk and Apply Resources. 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0545 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose: Development and validation of a personalized breast cancer risk

  6. Risk is not flat. Comprehensive approach to multidimensional risk management in ST-elevation myocardial infarction treated with primary angioplasty (ANIN STEMI Registry).

    PubMed

    Kruk, Mariusz; Przyłuski, Jakub; Kalińczuk, Lukasz; Pręgowski, Jerzy; Kaczmarska, Edyta; Petryka, Joanna; Kępka, Cezary; Bekta, Paweł; Chmielak, Zbigniew; Demkow, Marcin; Ciszewski, Andrzej; Karcz, Maciej; Kłopotowski, Mariusz; Witkowski, Adam; Rużyłło, Witold

    2013-01-01

    Current risk assessment concepts in ST-elevation myocardial infarction (STEMI) are suboptimal for guiding clinical management. To elaborate a composite risk management concept for STEMI, enhancing clinical decision making. 1995 unselected, registry patients with STEMI treated with primary percutaneous coronary intervention (pPCI) (mean age 60.1 years, 72.1% men) were included in the study. The independent risk markers were grouped by means of factor analysis, and the appropriate hazards were identified. In-hospital death was the primary outcome, observed in 95 (4.7%) patients. Independent predictors of mortality included age, leukocytosis, hyperglycemia, tachycardia, low blood pressure, impaired renal function, Killip > 1, anemia, and history of coronary disease. The factor analysis identified two significant clusters of risk markers: 1. age-anemia- impaired renal function, interpreted as the patient-related hazard; and 2. tachycardia-Killip > 1-hyperglycemia-leukocytosis, interpreted as the event-related (hemodynamic) hazard. The hazard levels (from low to high) were defined based on the number of respective risk markers. Patient-related hazard determined outcomes most significantly within the low hemodynamic hazard group. The dissection of the global risk into the combination of patient- and event-related (hemodynamic) hazards allows comprehensive assessment and management of several, often contradictory sources of risk in STEMI. The cohort of high-risk STEMI patients despite hemodynamically trivial infarction face the most suboptimal outcomes under the current invasive management strategy.

  7. Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction

    PubMed Central

    Ayalew, M; Le-Niculescu, H; Levey, D F; Jain, N; Changala, B; Patel, S D; Winiger, E; Breier, A; Shekhar, A; Amdur, R; Koller, D; Nurnberger, J I; Corvin, A; Geyer, M; Tsuang, M T; Salomon, D; Schork, N J; Fanous, A H; O'Donovan, M C; Niculescu, A B

    2012-01-01

    We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein–coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the

  8. Framework for Human Health Risk Assessment to Inform Decision Making

    EPA Pesticide Factsheets

    The purpose of this document is to describe a Framework for conducting human health risk assessments that are responsive to the needs of decision‐making processes in the U.S. Environmental Protection Agency (EPA).

  9. Evaluation of Human Performance Issues for Fire Risk

    SciTech Connect

    Bley, Dennis C.; Cooper, Susan E.; Forester, John A.; Kolaczkowski, Alan M.; Ramey-Smith, Ann; Thompson, Catherine M.; Whitehead, Donnie W.; Wreathall, John

    1999-05-04

    This paper summarizes the current status of the treatment of human reliability in fire risk analyses for nuclear power plants and identifies areas that need to be addressed. A new approach is suggested to improve the modeling.

  10. THE ROLE OF EXPOSURE ANALYSIS IN HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    This presentation will cover the basic methodologies used for assessing human exposures to environmental pollutants, and some of the scientific challenges involved in conducting exposure and risk assessments in support of regulatory evaluations.

  11. Human Health Toxicity Values in Superfund Risk Assessments

    EPA Pesticide Factsheets

    This memorandum revises the hierarchy of human health toxicity values generally recommended for use inr isk assessments, originally presented in Risk Assessment Guidance for Superfund Volume I, Part A.

  12. Risks to aquatic organisms posed by human pharmaceutical use

    EPA Science Inventory

    In order to help prioritize future research efforts within the US, risks associated with exposure to human prescription pharmaceutical residues in wastewater were estimated from marketing and pharmacological data. Masses of 371 active pharmaceutical ingredients (APIs) dispensed ...

  13. Risks to aquatic organisms posed by human pharmaceutical use

    EPA Science Inventory

    In order to help prioritize future research efforts within the US, risks associated with exposure to human prescription pharmaceutical residues in wastewater were estimated from marketing and pharmacological data. Masses of 371 active pharmaceutical ingredients (APIs) dispensed ...

  14. THE ROLE OF EXPOSURE ANALYSIS IN HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    This presentation will cover the basic methodologies used for assessing human exposures to environmental pollutants, and some of the scientific challenges involved in conducting exposure and risk assessments in support of regulatory evaluations.

  15. Prognostic stratification of patients with vasospastic angina: a comprehensive clinical risk score developed by the Japanese Coronary Spasm Association.

    PubMed

    Takagi, Yusuke; Takahashi, Jun; Yasuda, Satoshi; Miyata, Satoshi; Tsunoda, Ryusuke; Ogata, Yasuhiro; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Sato, Toshiaki; Ogawa, Satoshi; Kubo, Norifumi; Momomura, Shin-Ichi; Ogawa, Hisao; Shimokawa, Hiroaki

    2013-09-24

    The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide

    PubMed Central

    Chen, Alyce A.; Gheit, Tarik; Franceschi, Silvia

    2015-01-01

    ABSTRACT Human papillomavirus 18 (HPV18) is the second most carcinogenic HPV type, after HPV16, and it accounts for approximately 12% of squamous cell carcinoma (SCC) as well as 37% of adenocarcinoma (ADC) of the cervix worldwide. We aimed to evaluate the worldwide diversity and carcinogenicity of HPV18 genetic variants by sequencing the entire long control region (LCR) and the E6 open reading frame of 711 HPV18-positive cervical samples from 39 countries, taking advantage of the International Agency for Research on Cancer biobank. A total of 209 unique HPV18 sequence variants were identified that formed three phylogenetic lineages (A, B, and C). A and B lineages each divided into four sublineages, including a newly identified candidate B4 sublineage. The distribution of lineages varied by geographical region, with B and C lineages found principally in Africa. HPV18 (sub)lineages were compared between 453 cancer cases and 236 controls, as well as between 81 ADC and 160 matched SCC cases. In region-stratified analyses, there were no significant differences in the distribution of HPV18 variant lineages between cervical cancer cases and controls or between ADC and SCC. In conclusion, our findings do not support the role of HPV18 (sub)lineages for discriminating cancer risk or explaining why HPV18 is more strongly linked with ADC than SCC. IMPORTANCE This is the largest and most geographically/ethnically diverse study of the genetic variation of HPV18 to date, providing a comprehensive reference for phylogenetic classification of HPV18 sublineages for epidemiological and biological studies. PMID:26269181

  17. Updated Human Health Risk Analyses for Chlorpyrifos

    EPA Pesticide Factsheets

    EPA has revised the human health hazard assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos.

  18. Influence of graphic format on comprehension of risk information among American Indians.

    PubMed

    Sprague, Debra; LaVallie, Donna L; Wolf, Fredric M; Jacobsen, Clemma; Sayson, Kirsten; Buchwald, Dedra

    2011-01-01

    Presentation of risk information influences patients' ability to interpret health care options. Little is known about this relationship between risk presentation and interpretation among American Indians. Three hundred American Indian employees on a western American Indian reservation were invited to complete an anonymous written survey. All surveys included a vignette presenting baseline risk information about a hypothetical cancer and possible benefits of 2 prevention plans. Risk interpretation was assessed by correct answers to 3 questions evaluating the risk reduction associated with the plans. Numeric information was the same in all surveys, but framing varied; half expressed prevention benefits in terms of relative risk reduction and half in terms of absolute risk reduction. All surveys used text to describe the benefits of the 2 plans, but half included a graphic image. Surveys were distributed randomly. Responses were analyzed using binary logistic regression with the robust variance estimator to account for clustering of outcomes within participant. Use of a graphic image was associated with higher odds of correctly answering 3 risk interpretation questions (odds ratio = 2.5, 95% confidence interval = 1.5-4.0, P < 0.001) compared to the text-only format. These findings were similar to those of previous studies carried out in the general population. Neither framing information as relative compared to absolute risk nor the interaction between graphic image and relative risk presentation was associated with risk interpretation. One type of graphic image was associated with increased understanding of risk in a small sample of American Indian adults. The authors recommend further investigation of the effectiveness of other types of graphic displays for conveying health risk information to this population.

  19. Human health risk assessment of heavy metals in urban stormwater.

    PubMed

    Ma, Yukun; Egodawatta, Prasanna; McGree, James; Liu, An; Goonetilleke, Ashantha

    2016-07-01

    Toxic chemical pollutants such as heavy metals (HMs) are commonly present in urban stormwater. These pollutants can pose a significant risk to human health and hence a significant barrier for urban stormwater reuse. The primary aim of this study was to develop an approach for quantitatively assessing the risk to human health due to the presence of HMs in stormwater. This approach will lead to informed decision making in relation to risk management of urban stormwater reuse, enabling efficient implementation of appropriate treatment strategies. In this study, risks to human health from heavy metals were assessed as hazard index (HI) and quantified as a function of traffic and land use related parameters. Traffic and land use are the primary factors influencing heavy metal loads in the urban environment. The risks posed by heavy metals associated with total solids and fine solids (<150μm) were considered to represent the maximum and minimum risk levels, respectively. The study outcomes confirmed that Cr, Mn and Pb pose the highest risks, although these elements are generally present in low concentrations. The study also found that even though the presence of a single heavy metal does not pose a significant risk, the presence of multiple heavy metals could be detrimental to human health. These findings suggest that stormwater guidelines should consider the combined risk from multiple heavy metals rather than the threshold concentration of an individual species. Furthermore, it was found that risk to human health from heavy metals in stormwater is significantly influenced by traffic volume and the risk associated with stormwater from industrial areas is generally higher than that from commercial and residential areas.

  20. Secondary "At-Risk" Students' Perceptions of Experiences within a Comprehensive High School and a Continuation High/Alternative High School

    ERIC Educational Resources Information Center

    Loomis, Corey Campbell

    2011-01-01

    Comprehensive high schools have been unable to meet the needs of all students (Cotton, 2004). Students face challenges, and some have been labeled "at risk" for various reasons. These students constitute a unique group who often require more time, energy, and resources than large, comprehensive schools can offer. Consequently, they fall behind on…

  1. Secondary "At-Risk" Students' Perceptions of Experiences within a Comprehensive High School and a Continuation High/Alternative High School

    ERIC Educational Resources Information Center

    Loomis, Corey Campbell

    2011-01-01

    Comprehensive high schools have been unable to meet the needs of all students (Cotton, 2004). Students face challenges, and some have been labeled "at risk" for various reasons. These students constitute a unique group who often require more time, energy, and resources than large, comprehensive schools can offer. Consequently, they fall behind on…

  2. Comprehensive coronary risk determination in primary prevention: an imaging and clinical based definition combining computed tomographic coronary artery calcium score and national cholesterol education program risk score.

    PubMed

    Nasir, Khurram; Vasamreddy, Chandra; Blumenthal, Roger S; Rumberger, John A

    2006-06-16

    Cardiovascular disease (CVD) is the leading cause of mortality and a major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD deaths. Currently estimation of risk in primary prevention is based on the Framingham risk equations, which inputs traditional risk factors and is helpful in predicting the development of CHD in asymptomatic individuals. However many individuals suffer events in the absence of established risk factors for atherosclerosis and broad based population risk estimations may have little precision when applied to a given individual. To meet the challenge of CHD risk assessment, several tools have been developed to identify atherosclerotic disease in its preclinical stages. This paper aims to incorporate information from coronary artery calcification (CAC) scoring from a computed tomographic "heartscan" (using Electron Beam Tomography (EBT) as the validated prototype) along with current Framingham risk profiling in order to refine risk on an absolute scale by combining imaging and clinical data to affect a more comprehensive calculation of absolute risk in a given individual. For CAC scores above the 75th percentile but <90th percentile, 10 years is added to chronological age, and for CAC scores above the 90th percentile, 20 years is added to current chronological age. Among those in whom a positive CAC score is the norm such as older individuals (men> or =55 years, women> or =65 years) a CAC = 0 will result in an age point score corresponding to the age-group whose median CAC score is zero i.e., 40-44 years for men and 55-59 years for women. The utilization of CAC scores allows the inclusion of sub-clinical disease definition into the context of modifiable risk factors as well as identifies high-risk individuals requiring aggressive treatment.

  3. PATRIC: the Comprehensive Bacterial Bioinformatics Resource with a Focus on Human Pathogenic Species ▿ ‡ #

    PubMed Central

    Gillespie, Joseph J.; Wattam, Alice R.; Cammer, Stephen A.; Gabbard, Joseph L.; Shukla, Maulik P.; Dalay, Oral; Driscoll, Timothy; Hix, Deborah; Mane, Shrinivasrao P.; Mao, Chunhong; Nordberg, Eric K.; Scott, Mark; Schulman, Julie R.; Snyder, Eric E.; Sullivan, Daniel E.; Wang, Chunxia; Warren, Andrew; Williams, Kelly P.; Xue, Tian; Seung Yoo, Hyun; Zhang, Chengdong; Zhang, Yan; Will, Rebecca; Kenyon, Ronald W.; Sobral, Bruno W.

    2011-01-01

    Funded by the National Institute of Allergy and Infectious Diseases, the Pathosystems Resource Integration Center (PATRIC) is a genomics-centric relational database and bioinformatics resource designed to assist scientists in infectious-disease research. Specifically, PATRIC provides scientists with (i) a comprehensive bacterial genomics database, (ii) a plethora of associated data relevant to genomic analysis, and (iii) an extensive suite of computational tools and platforms for bioinformatics analysis. While the primary aim of PATRIC is to advance the knowledge underlying the biology of human pathogens, all publicly available genome-scale data for bacteria are compiled and continually updated, thereby enabling comparative analyses to reveal the basis for differences between infectious free-living and commensal species. Herein we summarize the major features available at PATRIC, dividing the resources into two major categories: (i) organisms, genomes, and comparative genomics and (ii) recurrent integration of community-derived associated data. Additionally, we present two experimental designs typical of bacterial genomics research and report on the execution of both projects using only PATRIC data and tools. These applications encompass a broad range of the data and analysis tools available, illustrating practical uses of PATRIC for the biologist. Finally, a summary of PATRIC's outreach activities, collaborative endeavors, and future research directions is provided. PMID:21896772

  4. A comprehensive simulator of the human respiratory system: validation with experimental and simulated data.

    PubMed

    Chiari, L; Avanzolini, G; Ursino, M

    1997-01-01

    A comprehensive model of oxygen (O2) and carbon dioxide (CO2) exchange, transport, and storage in the adult human is presented, and its ability to provide realistic responses under different physiological conditions is evaluated. The model comprises three compartments (i.e., lung, body tissue, and brain tissue) and incorporates a controller that adjusts alveolar ventilation and cardiac output dynamically integrating stimuli coming from peripheral and central chemoreceptors. A new realistic CO2 dissociation curve based on a two-buffer model of acid-base chemical regulation is included. In addition, the model explicitly considers relevant physiological factors such as buffer base, the nonlinear interaction between the O2 and CO2 chemoreceptor responses, pulmonary shunt, dead space, variable time delays, and Bohr and Haldane effects. Model simulations provide results consistent with both dynamic and steady-state responses measured in subjects undergoing inhalation of high CO2 (hypercapnia) or low O2 (hypoxia) and subsequent recovery. An analysis of the results indicates that the proposed model fits the experimental data of ventilation and gas partial pressures as some meaningful simulators now available and in a very large range of gas intake fractions. Moreover, it also provides values of blood concentrations of CO2, HCO3-, and hydrogen ions in good agreement with more complex simulators characterized by an implicit formulation of the CO2 dissociation curve. In the experimental conditions analyzed, the model seems to represent a single theoretical framework able to appropriately describe the different phenomena involved in the control of respiration.

  5. Comprehensive quantification of ceramide species in human stratum corneum[S

    PubMed Central

    Masukawa, Yoshinori; Narita, Hirofumi; Sato, Hirayuki; Naoe, Ayano; Kondo, Naoki; Sugai, Yoshiya; Oba, Tsuyoshi; Homma, Rika; Ishikawa, Junko; Takagi, Yutaka; Kitahara, Takashi

    2009-01-01

    One of the key challenges in lipidomics is to quantify lipidomes of interest, as it is practically impossible to collect all authentic materials covering the targeted lipidomes. For diverse ceramides (CER) in human stratum corneum (SC) that play important physicochemical roles in the skin, we developed a novel method for quantification of the overall CER species by improving our previously reported profiling technique using normal-phase liquid chromatog­raphy-electrospray ionization-mass spectrometry (NPLC-ESI-MS). The use of simultaneous selected ion monitoring measurement of as many as 182 kinds of molecular-related ions enables the highly sensitive detection of the overall CER species, as they can be analyzed in only one SC-stripped tape as small as 5 mm × 10 mm. To comprehensively quantify CERs, including those not available as authentic species, we designed a procedure to estimate their levels using relative responses of representative authentic species covering the species targeted, considering the systematic error based on intra-/inter-day analyses. The CER levels obtained by this method were comparable to those determined by conventional thin-layer chromatography (TLC), which guarantees the validity of this method. This method opens lipidomics approaches for CERs in the SC. PMID:19349641

  6. Phase-locked responses to speech in human auditory cortex are enhanced during comprehension.

    PubMed

    Peelle, Jonathan E; Gross, Joachim; Davis, Matthew H

    2013-06-01

    A growing body of evidence shows that ongoing oscillations in auditory cortex modulate their phase to match the rhythm of temporally regular acoustic stimuli, increasing sensitivity to relevant environmental cues and improving detection accuracy. In the current study, we test the hypothesis that nonsensory information provided by linguistic content enhances phase-locked responses to intelligible speech in the human brain. Sixteen adults listened to meaningful sentences while we recorded neural activity using magnetoencephalography. Stimuli were processed using a noise-vocoding technique to vary intelligibility while keeping the temporal acoustic envelope consistent. We show that the acoustic envelopes of sentences contain most power between 4 and 7 Hz and that it is in this frequency band that phase locking between neural activity and envelopes is strongest. Bilateral oscillatory neural activity phase-locked to unintelligible speech, but this cerebro-acoustic phase locking was enhanced when speech was intelligible. This enhanced phase locking was left lateralized and localized to left temporal cortex. Together, our results demonstrate that entrainment to connected speech does not only depend on acoustic characteristics, but is also affected by listeners' ability to extract linguistic information. This suggests a biological framework for speech comprehension in which acoustic and linguistic cues reciprocally aid in stimulus prediction.

  7. HOCOMOCO: a comprehensive collection of human transcription factor binding sites models

    PubMed Central

    Kulakovskiy, Ivan V.; Medvedeva, Yulia A.; Schaefer, Ulf; Kasianov, Artem S.; Vorontsov, Ilya E.; Bajic, Vladimir B.; Makeev, Vsevolod J.

    2013-01-01

    Transcription factor (TF) binding site (TFBS) models are crucial for computational reconstruction of transcription regulatory networks. In existing repositories, a TF often has several models (also called binding profiles or motifs), obtained from different experimental data. Having a single TFBS model for a TF is more pragmatic for practical applications. We show that integration of TFBS data from various types of experiments into a single model typically results in the improved model quality probably due to partial correction of source specific technique bias. We present the Homo sapiens comprehensive model collection (HOCOMOCO, http://autosome.ru/HOCOMOCO/, http://cbrc.kaust.edu.sa/hocomoco/) containing carefully hand-curated TFBS models constructed by integration of binding sequences obtained by both low- and high-throughput methods. To construct position weight matrices to represent these TFBS models, we used ChIPMunk software in four computational modes, including newly developed periodic positional prior mode associated with DNA helix pitch. We selected only one TFBS model per TF, unless there was a clear experimental evidence for two rather distinct TFBS models. We assigned a quality rating to each model. HOCOMOCO contains 426 systematically curated TFBS models for 401 human TFs, where 172 models are based on more than one data source. PMID:23175603

  8. Phase-Locked Responses to Speech in Human Auditory Cortex are Enhanced During Comprehension

    PubMed Central

    Peelle, Jonathan E.; Gross, Joachim; Davis, Matthew H.

    2013-01-01

    A growing body of evidence shows that ongoing oscillations in auditory cortex modulate their phase to match the rhythm of temporally regular acoustic stimuli, increasing sensitivity to relevant environmental cues and improving detection accuracy. In the current study, we test the hypothesis that nonsensory information provided by linguistic content enhances phase-locked responses to intelligible speech in the human brain. Sixteen adults listened to meaningful sentences while we recorded neural activity using magnetoencephalography. Stimuli were processed using a noise-vocoding technique to vary intelligibility while keeping the temporal acoustic envelope consistent. We show that the acoustic envelopes of sentences contain most power between 4 and 7 Hz and that it is in this frequency band that phase locking between neural activity and envelopes is strongest. Bilateral oscillatory neural activity phase-locked to unintelligible speech, but this cerebro-acoustic phase locking was enhanced when speech was intelligible. This enhanced phase locking was left lateralized and localized to left temporal cortex. Together, our results demonstrate that entrainment to connected speech does not only depend on acoustic characteristics, but is also affected by listeners’ ability to extract linguistic information. This suggests a biological framework for speech comprehension in which acoustic and linguistic cues reciprocally aid in stimulus prediction. PMID:22610394

  9. Ethical and Human Rights Foundations of Health Policy: Lessons from Comprehensive Reform in Mexico.

    PubMed

    Frenk, Julio; Gómez-Dantés, Octavio

    2015-12-10

    This paper discusses the use of an explicit ethical and human rights framework to guide a reform intended to provide universal and comprehensive social protection in health for all Mexicans, independently of their socio-economic status or labor market condition. This reform was designed, implemented, and evaluated by making use of what Michael Reich has identified as the three pillars of public policy: technical, political, and ethical. The use of evidence and political strategies in the design and negotiation of the Mexican health reform is briefly discussed in the first part of this paper. The second part examines the ethical component of the reform, including the guiding concept and values, as well as the specific entitlements that gave operational meaning to the right to health care that was enshrined in Mexico's 1983 Constitution. The impact of this rights-based health reform, measured through an external evaluation, is discussed in the final section. The main message of this paper is that a clear ethical framework, combined with technical excellence and political skill, can deliver major policy results.

  10. [Teaching design and practice of human blood type traits in genetics comprehensive laboratory course].

    PubMed

    Zhao, Jian; Hu, Dongmei; Yu, Dade; Dong, Mingliang; Li, Yun; Fan, Yingming; Wang, Yanwei; Zhang, Jinfeng

    2016-05-01

    Comprehensive laboratory courses, which enable students to aptly apply theoretic knowledge and master experiment skills, play an important role in the present educational reform of laboratory courses. We utilized human ABO blood type as the experimental subject, and designed the experiment--"Molecular Genotyping of Human ABO Blood Type and Analysis of Population Genetic Equilibrium". In the experiment, DNA in mucosal cells is extracted from students' saliva, and each student's genotype is identified using a series of molecular genetics technologies, including PCR amplification of target fragments, enzymatic digestion, and electrophoretic separation. Then, taking the whole class as an analogous Mendel population, a survey of genotype frequency of ABO blood type is conducted, followed with analyses of various population genetic parameters using Popgene. Through the open laboratory course, students can not only master molecular genetic experimental skills, but also improve their understanding of theoretic knowledge through independent design and optimization of molecular techniques. After five years of research and practice, a stable experimental system of molecular genetics has been established to identify six genotypes of ABO blood types, namely I(A)I(A), I(A)i, I(B)I(B), I(B)i, I(A)I(B) and ii. Laboratory courses of molecular and population genetics have been integrated by calculating the frequencies of the six genotypes and three multiple alleles and testing population genetic equilibrium. The goal of the open laboratory course with independent design and implementation by the students has been achieved. This laboratory course has proved effective and received good reviews from the students. It could be applied as a genetics laboratory course for the biology majors directly, and its ideas and methods could be promoted and applied to other biological laboratory courses.

  11. Second prize: Comprehensive proteomic analysis of human calcium oxalate monohydrate kidney stone matrix.

    PubMed

    Canales, Benjamin K; Anderson, Lorraine; Higgins, Leeann; Slaton, Joel; Roberts, Ken P; Liu, Nathan; Monga, Manoj

    2008-06-01

    Previous efforts to identify the protein content of stone matrix have been limited by the lack of technology necessary to analyze the highly insoluble protein-crystalline complex. Our study objective is to characterize the matrix of calcium oxalate monohydrate (COM) stones using a comprehensive proteomics approach. Seven pure COM stones were powdered, and proteins were extracted using four different buffer solutions. Detergent cleanup spin columns or concentrators were used to remove detergent and to exchange buffers before trypsin digestion. Tryptic peptides were analyzed with reversed-phase, high-performance liquid chromatography (RP-HPLC) and tandem mass spectrometry (MS/MS) using a QSTAR Pulsar i quadrapole time of flight mass spectrometer. Tandem mass spectra were searched against National Center for Biotechnology Information human nonredundant database using ProteinPilot 1.0 software (Applied Biosystems, Inc.) for protein hits; peptide MS/MS spectra were manually inspected. Of the four buffers, only 2% sodium dodecyl sulfate (SDS) samples had normal HPLC and MS/MS elution patterns. We identified 68 distinct proteins with 95% confidence. More than 50 of the proteins have not been previously identified in stone matrix. Of particular note, a significant number of inflammatory proteins were identified, including immunoglobulins, defensin -3, clusterin, complement C3a, kininogen, and fibrinogen. SDS reducing buffer was efficient at solubilizing proteins from stone matrix for further MS-based proteomic analysis. A variety of cellular, structural, and plasma proteins comprise COM stone matrix. Several of the stone proteins are involved in cell injury pathways, which suggests that inflammation plays a role in human COM stone formation.

  12. Novel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues.

    PubMed

    Turtoi, Andrei; Dumont, Bruno; Greffe, Yannick; Blomme, Arnaud; Mazzucchelli, Gabriel; Delvenne, Philippe; Mutijima, Eugène Nzaramba; Lifrange, Eric; De Pauw, Edwin; Castronovo, Vincent

    2011-07-01

    The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer

  13. Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.

    PubMed

    Furukawa, Jun-ichi; Tsuda, Masumi; Okada, Kazue; Kimura, Taichi; Piao, Jinhua; Tanaka, Shinya; Shinohara, Yasuro

    2015-01-01

    Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.

  14. Assessing human health risk in the USDA forest service

    SciTech Connect

    Hamel, D.R.

    1990-12-31

    This paper identifies the kinds of risk assessments being done by or for the US Department of Agriculture (USDA) Forest Service. Summaries of data sources currently in use and the pesticide risk assessments completed by the agency or its contractors are discussed. An overview is provided of the agency`s standard operating procedures for the conduct of toxicological, ecological, environmental fate, and human health risk assessments.

  15. Human Research Program Human Health Countermeasures Element Bone and Muscle Risk Standing Review Panel (SRP)

    NASA Technical Reports Server (NTRS)

    Glowacki, Julie; Gregor, Robert

    2009-01-01

    The Bone and Muscle Risk Standing Review Panel (SRP) met at the NASA Johnson Space Center (JSC) on October 4-6, 2009 to discuss the areas of current and future research targeted by the Human Health Countermeasures (HHC) Element of the Human Research Program (HRP). Using evidence-based knowledge as a background for identified risks to astronaut health and performance, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Bone and Muscle Risk SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the Panel's review. The Bone and Muscle Risk SRP consisted of scientists who are experts in muscle, bone, or both and could evaluate the existing evidence with sufficient knowledge of the potential effects of long duration exposure to microgravity. More important, although expertise in basic science is important, the SRP was requested to evaluate the practicality of the proposed efforts in light of the realistic demands placed on the HRP. In short, all tasks presented in the Integrated Research Plan (IRP) should address specific questions related to the challenges faced by the astronauts as a result of prolonged exposure to microgravity. All tasks proposed to fill the gaps in knowledge should provide applied, translational data necessary to answer the specific questions. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the panel charge, either as a group or in separate sessions for the Bone and Muscle Risk subgroups. The SRP made a final debriefing to the HRP Program Scientist, Dr. John B. Charles, on October 6, 2009. Taking the evidence and identified risks as givens, the SRP concluded that 1) integration of information should lead to a more comprehensive approach to identifying the gaps, 2) not all tasks addressed the gaps as

  16. Risk behaviours and comprehension among intravenous drug users volunteered for HIV vaccine trial.

    PubMed

    Pitisuttithum, P; Migasena, S; Laothai, A; Suntharasamai, P; Kumpong, C; Vanichseni, S

    1997-01-01

    Out of 91 volunteers enrolled for the HIV vaccine trial, only 33 volunteers were eligible for vaccination. Of 33 volunteers recruited, 59 per cent of them had incomes of more than 5,000 Baht/ month. The median duration of drug addicts was 15 years (range 1-26 years) and 42 per cent never used condoms during sexual intercourse. As far as consent comprehension was concerned, all of them understood.

  17. [Is avian influenza a risk for humans?].

    PubMed

    Allwinn, R; Doerr, H W

    2005-04-15

    Avian influenza is an infectious disease of birds, caused by type A strains of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide. Avian influenza viruses are mainly distributed by migratory birds. Different mammals like swine, horse and finally humans are susceptible for avian influenza viruses. The high possibility of genomic changes like gene shift and drift is caused by the segmented RNA genome. During the avian flu outbreak in East Asia at the end of 2003 the virus also killed several humans in Vietnam and Thailand. That avian influenza could also infect humans has been known since 1997. The H5N1 flu outbreak seemed successfully controlled, but currently new cases in poultry and humans in Vietnam, Thailand, China and Indonesia are recognized. Also another avian influenza A strain type H9N2 was prevalent in chickens of local markets in Hong Kong. Because of the natural virus reservoir like wild and/ or domesticated ducks and others, actually there is little chance of eradicating avian influenza. Furthermore the virus could mutate and jump to humans with the threat of a global influenza pandemic.

  18. Novel Threat-risk Index Using Probabilistic Risk Assessment and Human Reliability Analysis - Final Report

    SciTech Connect

    George A. Beitel

    2004-02-01

    In support of a national need to improve the current state-of-the-art in alerting decision makers to the risk of terrorist attack, a quantitative approach employing scientific and engineering concepts to develop a threat-risk index was undertaken at the Idaho National Engineering and Environmental Laboratory (INEEL). As a result of this effort, a set of models has been successfully integrated into a single comprehensive model known as Quantitative Threat-Risk Index Model (QTRIM), with the capability of computing a quantitative threat-risk index on a system level, as well as for the major components of the system. Such a threat-risk index could provide a quantitative variant or basis for either prioritizing security upgrades or updating the current qualitative national color-coded terrorist threat alert.

  19. Drug residues and endocrine disruptors in drinking water: risk for humans?

    PubMed

    Touraud, Evelyne; Roig, Benoit; Sumpter, John P; Coetsier, Clémence

    2011-11-01

    The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion. Copyright © 2011. Published by Elsevier GmbH.

  20. Incorporating human-triggered earthquake risks into energy and water policies

    NASA Astrophysics Data System (ADS)

    Klose, C. D.; Seeber, L.; Jacob, K. H.

    2010-12-01

    A comprehensive understanding of earthquake risks in urbanized regions requires an accurate assessment of both urban vulnerabilities and hazards from earthquakes, including ones whose timing might be affected by human activities. Socioeconomic risks associated with human-triggered earthquakes are often misconstrued and receive little scientific, legal, and public attention. Worldwide, more than 200 damaging earthquakes, associated with industrialization and urbanization, were documented since the 20th century. Geomechanical pollution due to large-scale geoengineering activities can advance the clock of earthquakes, trigger new seismic events or even shot down natural background seismicity. Activities include mining, hydrocarbon production, fluid injections, water reservoir impoundments and deep-well geothermal energy production. This type of geohazard has impacts on human security on a regional and national level. Some planned or considered future engineering projects raise particularly strong concerns about triggered earthquakes, such as for instance, sequestration of carbon dioxide by injecting it deep underground and large-scale natural gas production in the Marcellus shale in the Appalacian basin. Worldwide examples of earthquakes are discussed, including their associated losses of human life and monetary losses (e.g., 1989 Newcastle and Volkershausen earthquakes, 2001 Killari earthquake, 2006 Basel earthquake, 2010 Wenchuan earthquake). An overview is given on global statistics of human-triggered earthquakes, including depths and time delay of triggering. Lastly, strategies are described, including risk mitigation measures such as urban planning adaptations and seismic hazard mapping.

  1. Integrating Human Factors into Space Vehicle Processing for Risk Management

    NASA Technical Reports Server (NTRS)

    Woodbury, Sarah; Richards, Kimberly J.

    2008-01-01

    This presentation will discuss the multiple projects performed in United Space Alliance's Human Engineering Modeling and Performance (HEMAP) Lab, improvements that resulted from analysis, and the future applications of the HEMAP Lab for risk assessment by evaluating human/machine interaction and ergonomic designs.

  2. A 21st Century Roadmap for Human Health Risk Assessment

    EPA Science Inventory

    For decades human health risk assessment has depended primarily on animal testing to predict adverse effects in humans, but that paradigm has come under question because of calls for more accurate information, less use of animals, and more efficient use of resources. Moreover, t...

  3. A 21st Century Roadmap for Human Health Risk Assessment

    EPA Science Inventory

    For decades human health risk assessment has depended primarily on animal testing to predict adverse effects in humans, but that paradigm has come under question because of calls for more accurate information, less use of animals, and more efficient use of resources. Moreover, t...

  4. Critical medical humanities: embracing entanglement, taking risks.

    PubMed

    Viney, William; Callard, Felicity; Woods, Angela

    2015-06-01

    What can the medical humanities achieve? This paper does not seek to define what is meant by the medical humanities, nor to adjudicate the exact disciplinary or interdisciplinary knowledges it should offer, but rather to consider what it might be capable of doing. Exploring the many valences of the word 'critical', we argue here for a critical medical humanities characterised by: (i) a widening of the sites and scales of 'the medical' beyond the primal scene of the clinical encounter; (ii) greater attention not simply to the context and experience of health and illness, but to their constitution at multiple levels; (iii) closer engagement with critical theory, queer and disability studies, activist politics and other allied fields; (iv) recognition that the arts, humanities and social sciences are best viewed not as in service or in opposition to the clinical and life sciences, but as productively entangled with a 'biomedical culture'; and, following on from this, (v) robust commitment to new forms of interdisciplinary and cross-sector collaboration. We go on to introduce the five other articles published in this special issue of the journal, reflecting on the ways in which collaboration and critique are articulated in their analyses of immunology, critical neuroscience, toxicity, global clinical labour, and psychological coercion and workfare. As these articles demonstrate, embracing the complex role of critical collaborator--one based on notions of entanglement, rather than servility or antagonism--will, we suggest, develop the imaginative and creative heterodox qualities and practices which have long been recognised as core strengths of the medical humanities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Critical medical humanities: embracing entanglement, taking risks

    PubMed Central

    Viney, William; Callard, Felicity; Woods, Angela

    2015-01-01

    What can the medical humanities achieve? This paper does not seek to define what is meant by the medical humanities, nor to adjudicate the exact disciplinary or interdisciplinary knowledges it should offer, but rather to consider what it might be capable of doing. Exploring the many valences of the word ‘critical’, we argue here for a critical medical humanities characterised by: (i) a widening of the sites and scales of ‘the medical’ beyond the primal scene of the clinical encounter; (ii) greater attention not simply to the context and experience of health and illness, but to their constitution at multiple levels; (iii) closer engagement with critical theory, queer and disability studies, activist politics and other allied fields; (iv) recognition that the arts, humanities and social sciences are best viewed not as in service or in opposition to the clinical and life sciences, but as productively entangled with a ‘biomedical culture’; and, following on from this, (v) robust commitment to new forms of interdisciplinary and cross-sector collaboration. We go on to introduce the five other articles published in this special issue of the journal, reflecting on the ways in which collaboration and critique are articulated in their analyses of immunology, critical neuroscience, toxicity, global clinical labour, and psychological coercion and workfare. As these articles demonstrate, embracing the complex role of critical collaborator—one based on notions of entanglement, rather than servility or antagonism—will, we suggest, develop the imaginative and creative heterodox qualities and practices which have long been recognised as core strengths of the medical humanities. PMID:26052111

  6. Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis

    PubMed Central

    Bagnardi, V; Rota, M; Botteri, E; Tramacere, I; Islami, F; Fedirko, V; Scotti, L; Jenab, M; Turati, F; Pasquali, E; Pelucchi, C; Galeone, C; Bellocco, R; Negri, E; Corrao, G; Boffetta, P; La Vecchia, C

    2015-01-01

    Background: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. Methods: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose–response meta-regression models and investigated potential sources of heterogeneity. Results: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose–risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. Conclusions: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma. PMID:25422909

  7. Sunburns and risk of cutaneous melanoma: does age matter? A comprehensive meta-analysis.

    PubMed

    Dennis, Leslie K; Vanbeek, Marta J; Beane Freeman, Laura E; Smith, Brian J; Dawson, Deborah V; Coughlin, Julie A

    2008-08-01

    Sunburns are an important risk factor for melanoma and those occurring in childhood are often cited as posing the greatest risk. We conducted a meta-analysis to quantify the magnitude of association for melanoma and sunburns during childhood, adolescence, adulthood and over a lifetime. After reviewing over 1300 article titles and evaluating 270 articles in detail, we pooled odds ratios from 51 independent study populations for "ever" sunburned and risk of cutaneous melanoma. Among these, 26 studies reported results from dose-response analyses. Dose-response analyses were examined using both fixed-effects models and Bayesian random-effects models. An increased risk of melanoma was seen with increasing number of sunburns for all time-periods (childhood, adolescence, adulthood, and lifetime). In an attempt to understand how risk between life-periods compares, we also report these same linear models on a scale of five sunburns per decade for each life-period. The magnitude of risk for five sunburns per decade is highest for adult and lifetime sunburns. Overall, these results show an increased risk of melanoma with increasing number of sunburns during all life-periods, not just childhood. Prevention efforts should focus on reducing sunburns during all life-periods.

  8. Sunburns and risk of cutaneous melanoma, does age matter: a comprehensive meta-analysis

    PubMed Central

    Dennis, Leslie K.; VanBeek, Marta J.; Beane Freeman, Laura E.; Smith, Brian J.; Dawson, Deborah V.; Coughlin, Julie A.

    2010-01-01

    Purpose Sunburns are an important risk factor for melanoma and those occurring in childhood are often cited as posing the greatest risk. We conducted a meta-analysis to quantify the magnitude of association for melanoma and sunburns during childhood, adolescence, adulthood and over a lifetime. Methods After reviewing over 1300 article titles and evaluating 270 articles in detail, we pooled ORs from 51 independent study populations for “ever” sunburned and risk of cutaneous melanoma. Among these, 26 studies reported results from dose-response analyses. Dose-response analyses were examined using both fixed-effects models and Bayesian random-effects models. Results An increased risk of melanoma was seen with increasing number of sunburns for all time-periods (childhood, adolescence, adulthood and lifetime). In an attempt to understand how risk between life-periods compares, we also report these same linear models on a scale of 5 sunburns per decade for each life-period. The magnitude of risk for 5 sunburns per decade is highest for adult and lifetime sunburns. Conclusions Overall, these results show an increased risk of melanoma with increasing number of sunburns during all life-periods, not just childhood. Prevention efforts should focus on reducing sunburns during all life-periods. PMID:18652979

  9. The Importance of Human Reliability Analysis in Human Space Flight: Understanding the Risks

    NASA Technical Reports Server (NTRS)

    Hamlin, Teri L.

    2010-01-01

    HRA is a method used to describe, qualitatively and quantitatively, the occurrence of human failures in the operation of complex systems that affect availability and reliability. Modeling human actions with their corresponding failure in a PRA (Probabilistic Risk Assessment) provides a more complete picture of the risk and risk contributions. A high quality HRA can provide valuable information on potential areas for improvement, including training, procedural, equipment design and need for automation.

  10. Numeracy skill and the communication, comprehension, and use of risk-benefit information.

    PubMed

    Peters, Ellen; Hibbard, Judith; Slovic, Paul; Dieckmann, Nathan

    2007-01-01

    Current health care policy emphasizes improving health outcomes and the efficacy of health care delivery by supporting informed consumer choices. At the same time, health information often involves uncertainty, and many people may lack the skills and knowledge to process this information, manage their health and health care, and make informed choices. Innumeracy, an element of poor health literacy, is associated with the comprehension and use of important health information. We review this literature and examine what can be done to help less numerate people act more effectively and take charge of their health.

  11. Risk assessment and anesthetic management of patients with Williams syndrome: a comprehensive review.

    PubMed

    Matisoff, Andrew J; Olivieri, Laura; Schwartz, Jamie M; Deutsch, Nina

    2015-12-01

    Since the first description in 1961, several case reports have documented an increased incidence of anesthesia-related cardiac arrest in patients with Williams-Beuren syndrome, commonly known as Williams syndrome (WS). Widespread arteriopathy secondary to an elastin gene defect results in various cardiac defects, including supravalvar aortic stenosis (SVAS) and coronary artery anomalies, which can increase the risk of myocardial ischemia. Even though patients with WS are known to have increased risk of adverse events during anesthesia and sedation, they often undergo several procedures that require anesthesia during their lifetimes, and cases of perianesthetic cardiac arrest continue to be reported. To date, no prospective studies have been reported that quantify anesthetic risk in individual patients with WS. In this article, we review the clinical manifestations of WS, propose a consensus, expert-informed method to estimate anesthetic risk based on the current literature, and provide recommendations for periprocedural management of this patient population. © 2015 John Wiley & Sons Ltd.

  12. Common breast cancer risk variants in the post-COGS era: a comprehensive review

    PubMed Central

    2013-01-01

    Breast cancer has a strong heritable component, with approximately 15% of cases exhibiting a family history of the disease. Mutations in genes such as BRCA1, BRCA2 and TP53 lead to autosomal dominant inherited cancer susceptibility and confer a high lifetime risk of breast cancers. Identification of mutations in these genes through clinical genetic testing enables patients to undergo screening and prevention strategies, some of which provide overall survival benefit. In addition, a number of mutant alleles have been identified in genes such as CHEK2, PALB2, ATM and BRIP1, which often display incomplete penetrance and confer moderate lifetime risks of breast cancer. Studies are underway to determine how to use the identification of mutations in these genes to guide clinical practice. Altogether, however, mutations in high and moderate penetrance genes probably account for approximately 25% of familial breast cancer risk; the remainder may be due to mutations in as yet unidentified genes or lower penetrance variants. Common low penetrance alleles, which have been mainly identified through genome-wide association studies (GWAS), are generally present at 10 to 50% population frequencies and confer less than 1.5-fold increases in breast cancer risk. A number of single nucleotide polymorphisms (SNPs) have been identified and risk associations extensively replicated in populations of European ancestry, the number of which has substantially increased as a result of GWAS performed by the Collaborative Oncological Gene–environment Study consortium. It is now estimated that 28% of familial breast cancer risk is explained by common breast cancer susceptibility loci. In some cases, SNP associations may be specific to different subsets of women with breast cancer, as defined by ethnicity or estrogen receptor status. Although not yet clinically established, it is hoped that identification of common risk variants may eventually allow identification of women at higher risk of

  13. Comprehensive Population-Specific Marker Panel for Early Prostate Cancer Diagnostics and Risk Assessment

    DTIC Science & Technology

    2014-08-01

    cultural and lifestyle population specific biomarkers and factors will provided a valuable PCa screening and risk assessment tool. The PI genotyped 528...significantly associated with prostate cancer risk associated with one of the SNPs in African American men was found in obese men only; if was not...seen in either non- obese African American men or European American men regardless of their body mass. The PI has proposed a concept of the increased

  14. Alcohol consumption and the risk of Barrett’s esophagus: a comprehensive meta-analysis

    PubMed Central

    Ren, Lin-Lin; Yan, Ting-Ting; Wang, Zhen-Hua; Bian, Zhao-Lian; Yang, Fan; Hong, Jie; Chen, Hao-Yan; Fang, Jing-Yuan

    2015-01-01

    Several studies have been proposed to investigate the association between alcohol consumption and risk of Barrett’s esophagus (BE), but as of yet, no quantitative summary of the literature to clarify the relationship between them. In our study, twenty eligible cohort studies involving 42925 participants were identified. Combined relative risk (RR) ratios for the highest versus lowest alcohol consumption levels were calculated. The alcohol dose-response analysis was performed to investigate the association between the increment consumption of 10 g/d alcohol and the risk of developing BE. Subgroup analyses were used to examine heterogeneity across the studies. A combined RR of 0.98 (0.62–1.34) was found when comparing highest vs. lowest alcohol consumption levels for BE. An inverse association between alcohol and incidence of BE (RR 0.51; 95% CI: 0.055–0.96) was demonstrated in women. Moreover, Asian drinkers had a relative higher risk of BE (RR 1.34; 95% CI: 1.11–1.56) compared with Western drinkers. In conclusion, our results showed that overall alcohol consumption was not associated with increased BE incidence. The limited data available on alcohol consumption supports a tentative inversion of alcohol consumption with BE risk in women, while Asian drinkers tend to have a higher risk of BE. PMID:26542211

  15. Human milk, a concrete risk for infection?

    PubMed

    Lanari, M; Sogno Valin, P; Natale, F; Capretti, M G; Serra, L

    2012-10-01

    Breastfeeding should be considered a public health issue and the reference normative standards for infant feeding at least to the 6th month of life, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Numerous studies demonstrate that breastfeeding results in improved infant and maternal health. Moreover the reduction of the risk of severe retinopathy of prematurity, sepsis and necrotizing enterocolitis is particularly evident in preterm infants. There are a limited number of medical conditions in which breastfeeding is contraindicated, including some maternal infectious diseases. During breastfeeding the baby can be infected by mother's pathogens with several routes of transmission that can be considered, such as respiratory secretions and droplets (e.g. Adenovirus, Influenza virus, Respiratory Syncytial Virus, Haemophilus, Mycoplasma) direct contact with lesions in the breast and nipple (e.g. HSV 1-2, VZV, Treponema) and breast milk. Frequently, in case of infection, different routes of transmission are contemporary implicated. The basic assumption is that breastfeeding is rarely contraindicated during maternal infections, a few exceptions are HTVL-I and HIV in industrialized country. The theoretic risk for transmission trough breast milk should be discussed and balanced with the benefits of breast milk, so the mother and parents can make an informed decision concerning infant feeding.

  16. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    NASA Astrophysics Data System (ADS)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose

  17. Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

    PubMed

    Habbous, Steven; Chu, Karen P; Lau, Harold; Schorr, Melissa; Belayneh, Mathieos; Ha, Michael N; Murray, Scott; O'Sullivan, Brian; Huang, Shao Hui; Snow, Stephanie; Parliament, Matthew; Hao, Desiree; Cheung, Winson Y; Xu, Wei; Liu, Geoffrey

    2017-08-14

    The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012. © 2017 Canadian Medical Association or its licensors.

  18. Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation

    PubMed Central

    Habbous, Steven; Chu, Karen P.; Lau, Harold; Schorr, Melissa; Belayneh, Mathieos; Ha, Michael N.; Murray, Scott; O’Sullivan, Brian; Huang, Shao Hui; Snow, Stephanie; Parliament, Matthew; Hao, Desiree; Cheung, Winson Y.; Xu, Wei; Liu, Geoffrey

    2017-01-01

    BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012. PMID:28808115

  19. Comprehensive gene expression analysis of human NK cells and CD8(+) T lymphocytes.

    PubMed

    Obata-Onai, Aya; Hashimoto, Shin-ichi; Onai, Nobuyuki; Kurachi, Makoto; Nagai, Shigenori; Shizuno, Ken-ichi; Nagahata, Tomoyuki; Matsushima, Kouji; Mathushima, Kouji

    2002-10-01

    Cytotoxic lymphocytes, NK cells and CD8(+) T cells play a pivotal role in the host defense. To reveal the biological function of these cells through establishing a comprehensive gene expression profile, serial analysis of gene expression was performed in human peripheral blood NK cells and CD8(+) T cells. In total, 85,848 tags corresponding to >20,000 different transcripts were sequenced. The genes expressed abundantly in these libraries mostly consisted of genes encoding MHC class I and molecules related to protein synthesis. Among gene transcripts which related to cytotoxicity, granulysin, perforin, granzyme B and alpha-defensin 1 were highly expressed in NK cells. Resting CD8(+) T cells did not express the genes related to cytotoxicity, but expressed abundantly the genes encoding chemokines, tumor necrosis factor family. When CD8(+) T cells were sorted into naive, memory and effector subsets based on the expression of CD45RA and CD27, perforin and granzyme B were expressed in the CD45RA(+)CD27(-) effector subset. Alpha-defensin 1, one of the selectively expressed genes in NK cells, induced migration of naive CD8(+)CD45RA(+)CD27(+) T cells, but not memory CD8(+)CD45RA(-)CD27(+) or effector CD8(+)CD45RA(+)CD27(-) T cells. Furthermore, treatment with IL-15, a stimulator of NK cell development, differentiation, survival and cytotoxicity, rapidly enhanced the expression of alpha-defensin 1 in NK cells. The identification of the genes preferentially expressed in NK and CD8(+) T cell subsets may give important insights into the functions of these cells against virus infection and in tumor immunity.

  20. Developing a Gap Taxonomy to Address Crew Health Risks in NASA's Human Research Program

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.; Edwards, J. Michelle

    2009-01-01

    The mission of NASA's Human Research Program (HRP) is to understand and reduce the risk to crew health and performance in exploration missions. The HRP addresses 27 specific risks by identifying and then filling gaps in understanding the risks and in the ability to disposition the risks. The primary bases for identifying gaps have been past experience and requirements definition. This approach has been very effective in identifying some important, relevant gaps, but may be inadequate for identifying gaps outside the past experience base. We are exploring the use of a gap taxonomy as a comprehensive, underlying conceptual framework that allows a more systematic identification of gaps. The taxonomy is based on these stages in medical care: prediction, prevention, detection/diagnosis, treatment, monitoring, rehabilitation, and lifetime surveillance. This gap taxonomy approach identifies new gaps in HRP health risks. Many of the new gaps suggest risk reduction approaches that are more cost effective than present approaches. A major benefit of the gap taxonomy approach is to identify new, economical approaches that reduce the likelihood and/or consequence of a risk.

  1. Developing a Gap Taxonomy to Address Crew Health Risks in NASA's Human Research Program

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.; Edwards, J. Michelle

    2009-01-01

    The mission of NASA's Human Research Program (HRP) is to understand and reduce the risk to crew health and performance in exploration missions. The HRP addresses 27 specific risks by identifying and then filling gaps in understanding the risks and in the ability to disposition the risks. The primary bases for identifying gaps have been past experience and requirements definition. This approach has been very effective in identifying some important, relevant gaps, but may be inadequate for identifying gaps outside the past experience base. We are exploring the use of a gap taxonomy as a comprehensive, underlying conceptual framework that allows a more systematic identification of gaps. The taxonomy is based on these stages in medical care: prediction, prevention, detection/diagnosis, treatment, monitoring, rehabilitation, and lifetime surveillance. This gap taxonomy approach identifies new gaps in HRP health risks. Many of the new gaps suggest risk reduction approaches that are more cost effective than present approaches. A major benefit of the gap taxonomy approach is to identify new, economical approaches that reduce the likelihood and/or consequence of a risk.

  2. Predicting risk sensitivity in humans and lower animals: risk as variance or coefficient of variation.

    PubMed

    Weber, Elke U; Shafir, Sharoni; Blais, Ann-Renee

    2004-04-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk preference, the superiority of the CV over variance in predicting risk taking is not as strong. Two experiments show that people's risk sensitivity becomes strongly proportional to the CV when they learn about choice alternatives like other animals, by experiential sampling over time. Experience-based choices differ from choices when outcomes and probabilities are numerically described. Zipf's law as an ecological regularity and Weber's law as a psychological regularity may give rise to the CV as a measure of risk.

  3. A comprehensive examination of breast cancer risk loci in African American women

    PubMed Central

    Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Palmer, Julie R.; Olopade, Olufunmilayo I.; Huo, Dezheng; Adebamowo, Clement A.; Ogundiran, Temidayo; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Chanock, Stephen J.; Le Marchand, Loic; Kolonel, Laurence N.; Conti, David V.; Easton, Douglas; Henderson, Brian E.; Haiman, Christopher A.

    2014-01-01

    Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10−6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. PMID:24852375

  4. A new Web-based medical tool for assessment and prevention of comprehensive cardiovascular risk.

    PubMed

    Franchi, Daniele; Cini, Davide; Iervasi, Giorgio

    2011-01-01

    Multifactor cardiovascular disease is the leading cause of death; besides well-known cardiovascular risk factors, several emerging factors such as mental stress, diet type, and physical inactivity, have been associated to cardiovascular disease. To date, preventive strategies are based on the concept of absolute risk calculated by different algorithms and scoring systems. However, in general practice the patient's data collection represents a critical issue. A new multipurpose computer-based program has been developed in order to:1) easily calculate and compare the absolute cardiovascular risk by the Framingham, Procam, and Progetto Cuore algorithms; 2) to design a web-based computerized tool for prospective collection of structured data; 3) to support the doctor in the decision-making process for patients at risk according to recent international guidelines. During a medical consultation the doctor utilizes a common computer connected by Internet to a medical server where all the patient's data and software reside. The program evaluates absolute and relative cardiovascular risk factors, personalized patient's goals, and multiparametric trends, monitors critical parameter values, and generates an automated medical report. In a pilot study on 294 patients (47% males; mean age 60 ± 12 years [±SD]) the global time to collect data at first consultation was 13 ± 11 minutes which declined to 8 ± 7 minutes at the subsequent consultation. In 48.2% of cases the program revealed 2 or more primary risk factor parameters outside guideline indications and gave specific clinical suggestions to return altered parameters to target values. The web-based system proposed here may represent a feasible and flexible tool for clinical management of patients at risk of cardiovascular disease and for epidemiological research.

  5. Risk factors for febrile urinary tract infection in infants with prenatal hydronephrosis: comprehensive single center analysis.

    PubMed

    Zareba, Piotr; Lorenzo, Armando J; Braga, Luis H

    2014-05-01

    We assessed risk factors for urinary tract infection in children with prenatal hydronephrosis We identified 376 infants with prenatal hydronephrosis in an institutional database. The occurrence of febrile urinary tract infection in the first 2 years of life was ascertained by chart review. Febrile urinary tract infection was defined as a positive culture from a catheterized urine specimen in a patient with a fever of 38.0C or greater. Multivariate logistic regression was used to assess gender, circumcision status, hydronephrosis grade, vesicoureteral reflux grade and antibiotic prophylaxis as predictors of the risk of urinary tract infection. Included in analysis were 277 males and 99 females. Hydronephrosis was high grade in 128 infants (34.0%) and vesicoureteral reflux was present in 79 (21.0%). Antibiotic prophylaxis was prescribed in 60.4% of patients, preferentially to females vs males (70.7% vs 56.7%), those with high vs low grade hydronephrosis (70.3% vs 55.2%) and those with vs without vesicoureteral reflux (96.2% vs 50.8%). On multivariate analysis there was an association between high grade hydronephrosis and an increased risk of urinary tract infection (adjusted OR 2.40, 95% CI 1.26-4.56). Females (adjusted OR 3.16, 95% CI 0.98-10.19) and uncircumcised males (adjusted OR 3.63, 95% CI 1.18-11.22) were also at higher risk than circumcised males. Antibiotic prophylaxis was not associated with a decreased risk of urinary tract infection (adjusted OR 0.93, 95% CI 0.45-1.94). High grade hydronephrosis, female gender and uncircumcised status in males are independent risk factors for febrile urinary tract infection in infants with prenatal hydronephrosis. Antibiotic prophylaxis did not reduce the risk of urinary tract infection in the study group. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Risks of Mycotoxins from Mycoinsecticides to Humans.

    PubMed

    Hu, Qiongbo; Li, Fuxia; Zhang, Yuping

    2016-01-01

    There are more than thirty mycotoxins produced by fungal entomopathogens. Totally, they belong to two classes, NRP and PK mycotoxins. Most of mycotoxins have not been paid sufficient attention yet. Generally, mycotoxins do not exist in mycoinsecticide and might not be released to environments unless entomogenous fungus proliferates and produces mycotoxins in host insects or probably in plants. Some mycotoxins, destruxins as an example, are decomposed in host insects before they, with the insect's cadavers together, are released to environments. Many species of fungal entomopathogens have the endophytic characteristics. But we do not know if fungal entomopathogens produce mycotoxins in plants and release them to environments. On the contrary, the same mycotoxins produced by phytopathogens such as Fusarium spp. and Aspergillus spp. have been paid enough concerns. In conclusion, mycotoxins from mycoinsecticides have limited ways to enter environments. The risks of mycotoxins from mycoinsecticides contaminating foods are controllable.

  7. Risks of Mycotoxins from Mycoinsecticides to Humans

    PubMed Central

    Hu, Qiongbo; Li, Fuxia; Zhang, Yuping

    2016-01-01

    There are more than thirty mycotoxins produced by fungal entomopathogens. Totally, they belong to two classes, NRP and PK mycotoxins. Most of mycotoxins have not been paid sufficient attention yet. Generally, mycotoxins do not exist in mycoinsecticide and might not be released to environments unless entomogenous fungus proliferates and produces mycotoxins in host insects or probably in plants. Some mycotoxins, destruxins as an example, are decomposed in host insects before they, with the insect's cadavers together, are released to environments. Many species of fungal entomopathogens have the endophytic characteristics. But we do not know if fungal entomopathogens produce mycotoxins in plants and release them to environments. On the contrary, the same mycotoxins produced by phytopathogens such as Fusarium spp. and Aspergillus spp. have been paid enough concerns. In conclusion, mycotoxins from mycoinsecticides have limited ways to enter environments. The risks of mycotoxins from mycoinsecticides contaminating foods are controllable. PMID:27144161

  8. Quantitative risk assessment of human salmonellosis in Canadian broiler chicken breast from retail to consumption.

    PubMed

    Smadi, Hanan; Sargeant, Jan M

    2013-02-01

    The current quantitative risk assessment model followed the framework proposed by the Codex Alimentarius to provide an estimate of the risk of human salmonellosis due to consumption of chicken breasts which were bought from Canadian retail stores and prepared in Canadian domestic kitchens. The model simulated the level of Salmonella contamination on chicken breasts throughout the retail-to-table pathway. The model used Canadian input parameter values, where available, to represent risk of salmonellosis. From retail until consumption, changes in the concentration of Salmonella on each chicken breast were modeled using equations for growth and inactivation. The model predicted an average of 318 cases of salmonellosis per 100,000 consumers per year. Potential reasons for this overestimation were discussed. A sensitivity analysis showed that concentration of Salmonella on chicken breasts at retail and food hygienic practices in private kitchens such as cross-contamination due to not washing cutting boards (or utensils) and hands after handling raw meat along with inadequate cooking contributed most significantly to the risk of human salmonellosis. The outcome from this model emphasizes that responsibility for protection from Salmonella hazard on chicken breasts is a shared responsibility. Data needed for a comprehensive Canadian Salmonella risk assessment were identified for future research.

  9. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine

    PubMed Central

    Subbiah, Vivek; Wagner, Michael J.; McGuire, Mary F.; Sarwari, Nawid M.; Devarajan, Eswaran; Lewis, Valerae O.; Westin, Shanon; Kato, Shumei; Brown, Robert E.; Anderson, Pete

    2015-01-01

    Background Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Patients and Methods Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. Results In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2–16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Conclusions Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized

  10. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

    PubMed

    Subbiah, Vivek; Wagner, Michael J; McGuire, Mary F; Sarwari, Nawid M; Devarajan, Eswaran; Lewis, Valerae O; Westin, Shanon; Kato, Shumei; Brown, Robert E; Anderson, Pete

    2015-12-01

    Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are

  11. Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results.

    PubMed

    Burt, Lindsay M; Ying, Jian; Poppe, Matthew M; Suneja, Gita; Gaffney, David K

    2017-10-01

    To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not. The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973-2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4. There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19-1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31-1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods. There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A Comprehensive Index for Predicting Risk of Anemia from Patients' Diagnoses.

    PubMed

    Tuck, Matthew G; Alemi, Farrokh; Shortle, John F; Avramovic, Sanj; Hesdorffer, Charles

    2017-03-01

    This article demonstrates how time-dependent, interacting, and repeating risk factors can be used to create more accurate predictive medicine. In particular, we show how emergence of anemia can be predicted from medical history within electronic health records. We used the Veterans Affairs Informatics and Computing Infrastructure database to examine a retrospective cohort of 9,738,838 veterans over an 11-year period. Using International Clinical Diagnoses Version 9 codes organized into 25 major diagnostic categories, we measured progression of disease by examining changes in risk over time, interactions in risk of combination of diseases, and elevated risk associated with repeated hospitalization for the same diagnostic category. The maximum risk associated with each diagnostic category was used to predict anemia. The accuracy of the model was assessed using a validation cohort. Age and several diagnostic categories significantly contributed to the prediction of anemia. The largest contributors were health status ([Formula: see text] = -1075, t = -92, p < 0.000), diseases of the endocrine ([Formula: see text] = -1046, t = -87, p < 0.000), hepatobiliary ([Formula: see text] = -1043, t = -72, p < 0.000), kidney ([Formula: see text] = -1125, t = -111, p < 0.000), and respiratory systems ([Formula: see text] = -1151, t = -89, p < 0.000). The AUC for the additive model was 0.751 (confidence interval 74.95%-75.26%). The magnitude of AUC suggests that the model may assist clinicians in determining which patients are likely to develop anemia. The procedures used for examining changes in risk factors over time may also be helpful in other predictive medicine projects.

  13. The EPA's human exposure research program for assessing cumulative risk in communities

    PubMed Central

    Zartarian, Valerie G; Schultz, Bradley D

    2009-01-01

    Communities are faced with challenges in identifying and prioritizing environmental issues, taking actions to reduce their exposures, and determining their effectiveness for reducing human health risks. Additional challenges include determining what scientific tools are available and most relevant, and understanding how to use those tools; given these barriers, community groups tend to rely more on risk perception than science. The U.S. Environmental Protection Agency's Office of Research and Development, National Exposure Research Laboratory (NERL) and collaborators are developing and applying tools (models, data, methods) for enhancing cumulative risk assessments. The NERL's “Cumulative Communities Research Program” focuses on key science questions: (1) How to systematically identify and prioritize key chemical stressors within a given community?; (2) How to develop estimates of exposure to multiple stressors for individuals in epidemiologic studies?; and (3) What tools can be used to assess community-level distributions of exposures for the development and evaluation of the effectiveness of risk reduction strategies? This paper provides community partners and scientific researchers with an understanding of the NERL research program and other efforts to address cumulative community risks; and key research needs and opportunities. Some initial findings include the following: (1) Many useful tools exist for components of risk assessment, but need to be developed collaboratively with end users and made more comprehensive and user-friendly for practical application; (2) Tools for quantifying cumulative risks and impact of community risk reduction activities are also needed; (3) More data are needed to assess community- and individual-level exposures, and to link exposure-related information with health effects; and (4) Additional research is needed to incorporate risk-modifying factors (“non-chemical stressors”) into cumulative risk assessments. The products

  14. A functional magnetic resonance imaging study of listening comprehension of languages in human at 3 tesla-comprehension level and activation of the language areas.

    PubMed

    Nakai, T; Matsuo, K; Kato, C; Matsuzawa, M; Okada, T; Glover, G H; Moriya, T; Inui, T

    1999-03-19

    Passive listening comprehension of native and non-native language was investigated using high resolution functional magnetic resonance imaging (fMRI) at a static magnetic field strength of 3 tesla. Wernicke's area was activated by comprehensive and non-comprehensive languages indicating that this area is associated with common phonological processing of language. The task with comprehensive but non-native language activated Broca's area and angular gyrus most frequently. The activations in these areas may be related to demand in semantic and syntactic processing in listening comprehension. Supplementary motor area and pre-motor area were activated by comprehensive languages but not by non-comprehensive language. These motor controlling areas may be involved in semantic processing. Listening to comprehensive but non-native language seems to demand more networked co-processing.

  15. Humanized birth in high risk pregnancy: barriers and facilitating factors.

    PubMed

    Behruzi, Roxana; Hatem, Marie; Goulet, Lise; Fraser, William; Leduc, Nicole; Misago, Chizuru

    2010-02-01

    The medical model of childbearing assumes that a pregnancy always has the potential to turn into a risky procedure. In order to advocate humanized birth in high risk pregnancy, an important step involves the enlightenment of the professional's preconceptions on humanized birth in such a situation. The goal of this paper is to identify the professionals' perception of the potential obstacles and facilitating factors for the implementation of humanized care in high risk pregnancies. Twenty-one midwives, obstetricians, and health administrator professionals from the clinical and academic fields were interviewed in nine different sites in Japan from June through August 2008. The interviews were audio taped, and transcribed with the participants' consent. Data was subsequently analyzed using content analysis qualitative methods. Professionals concurred with the concept that humanized birth is a changing and promising process, and can often bring normality to the midst of a high obstetric risk situation. No practice guidelines can be theoretically defined for humanized birth in a high risk pregnancy, as there is no conflict between humanized birth and medical intervention in such a situation. Barriers encountered in providing humanized birth in a high risk pregnancy include factors such as: the pressure of being responsible for the safety of the mother and the fetus, lack of the women's active involvement in the decision making process and the heavy burden of responsibility on the physician's shoulders, potential legal issues, and finally, the lack of midwifery authority in providing care at high risk pregnancy. The factors that facilitate humanized birth in a high risk include: the sharing of decision making and other various responsibilities between the physicians and the women; being caring; stress management, and the fact that the evolution of a better relationship and communication between the health professional and the patient will lead to a stress

  16. Cigarette smoking and risk of lymphoma in adults: a comprehensive meta-analysis on Hodgkin and non-Hodgkin disease.

    PubMed

    Sergentanis, Theodoros N; Kanavidis, Prodromos; Michelakos, Theodoros; Petridou, Eleni Th

    2013-03-01

    The aim of the present meta-analysis was to examine comprehensively the association between smoking and lymphoma [Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL)] in adults. Eligible studies were identified, and pooled-effect estimates (odds ratios and relative risks) were calculated for ever, current and former smoking, separately by lymphoma subtype and gender. Metaregression analysis with percentage of male patients, mean age, duration (years of smoking), intensity (pack-years and cigarettes per day) and years since quitting was carried out. Out of the 50 eligible articles, 41 used a case-control design (20 143 NHL cases, 4340 HL cases and 61 517 controls), whereas nine used a cohort design (5748 incident NHL cases, 334 HL cases, total cohort size comprising 1 530 833 smokers). Ever smoking was associated with increased risk for NHL [pooled-effect estimate=1.05, 95% confidence interval (CI): 1.00-1.09] mainly because of the association with T-NHL (pooled-effect estimate=1.23, 95% CI: 1.09-1.38). Ever smoking was also associated with increased risk for HL (pooled-effect estimate=1.15, 95% CI: 1.02-1.30); sizeable associations were observed regarding both nodular sclerosis and mixed cellularity subtypes. Although male study arms pointed to predominantly increased risk for HL, metaregression did not confirm the male preponderance. Dose-response patterns were particularly evident for HL. Cigarette smoking seems to be associated with increased lymphoma risk, especially HL and T-NHL. Further well-designed studies seem to be needed so as to investigate the risk thoroughly, especially for T-NHL subentities, and the extent to which confounding may interfere with gender-related disparities.

  17. Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis.

    PubMed

    Li, Hui; Fu, Wei-Ping; Hong, Ze-Hui

    2013-03-01

    Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD). Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. However, the conclusions were controversial. We performed a comprehensive meta-analysis to clarify these findings. A total of 24 studies comprising 8,259 COPD patients and 42,883 controls were included. The overall results showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR, 1.33; 95% CI, 1.06-1.69). The subgroup analyses demonstrated this association in Caucasian individuals (OR, 1.61; 95% CI, 1.12-2.31) but not in Asian individuals. The 139 mutant heterozygote was significantly associated with a decreased risk of COPD in Asian populations (OR, 0.82; 95% CI, 0.68-0.99) but not in Caucasian populations. Pooled analyses revealed that the extremely slow (OR, 1.77; 95% CI, 1.23-2.55) and slow EPHX1 enzyme activity (OR, 1.44; 95% CI, 1.13-1.85) were associated with an increased risk of COPD, while the fast enzyme activity was not associated with a decreased risk of COPD. The stratified analysis demonstrated this association in Caucasian but not in Asian individuals. Furthermore, a modest difference in the risk of COPD was observed between the subgroups by using the cigarette smokers or the non-smokers as controls. A significant correlation between the two functional polymorphisms, T113C and A139G, of the EPHX1 gene and the enzyme activity and the individual's susceptibility to COPD was noted. In addition, the results supported a contribution of EPHX1 to the aetiology of COPD.

  18. Effectiveness of Comprehensive Professional Development for Teachers of At-Risk Preschoolers

    ERIC Educational Resources Information Center

    Landry, Susan H.; Anthony, Jason L.; Swank, Paul R.; Monseque-Bailey, Pauline

    2009-01-01

    This study compared effectiveness of "business as usual" to that of 4 professional development (PD) programs that targeted teachers of at-risk preschool children. A 2 x 2 design was used to cross mentoring and progress monitoring conditions among the 4 PD programs. Specifically, some teachers received both in-classroom mentoring and…

  19. Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review.

    PubMed

    Palomba, Stefano; Homburg, Roy; Santagni, Susanna; La Sala, Giovanni Battista; Orvieto, Raoul

    2016-11-04

    In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed.

  20. Managing Anger of At-Risk Students Using a Comprehensive Support Model

    ERIC Educational Resources Information Center

    Obiakor, Festus E.

    2006-01-01

    Many at-risk students face myriad problems that are pervasive, multifaceted, and socio-historical. These problems sometimes lead them to anger, frustration, hate, hostility, and rage. In the educational system, these problems frequently lead to stigmatization as well as misidentification, mislabeling, misplacement, and misinstruction. Ironically,…

  1. The Vermont Lighthouse School District Project: Comprehensive Planning for At-Risk Youth.

    ERIC Educational Resources Information Center

    Regional Laboratory for Educational Improvement of the Northeast & Islands, Andover, MA.

    The year-long Lighthouse District Planning Process culminated in the development of a plan that addresses the needs of at-risk students in the Burlington School District and the Orleans Southwest Supervisory Union in Vermont. This final report on the project also serves as a guide that can be used by other districts to construct a comprehensive…

  2. A 21st century roadmap for human health risk assessment.

    PubMed

    Pastoor, Timothy P; Bachman, Ammie N; Bell, David R; Cohen, Samuel M; Dellarco, Michael; Dewhurst, Ian C; Doe, John E; Doerrer, Nancy G; Embry, Michelle R; Hines, Ronald N; Moretto, Angelo; Phillips, Richard D; Rowlands, J Craig; Tanir, Jennifer Y; Wolf, Douglas C; Boobis, Alan R

    2014-08-01

    The Health and Environmental Sciences Institute (HESI)-coordinated Risk Assessment in the 21st Century (RISK21) project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment, and involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. This paper provides a brief overview of the tiered RISK21 framework called the roadmap and risk visualization matrix, and articulates the core principles derived by RISK21 participants that guided its development. Subsequent papers describe the roadmap and matrix in greater detail. RISK21 principles include focusing on problem formulation, utilizing existing information, starting with exposure assessment (rather than toxicity), and using a tiered process for data development. Bringing estimates of exposure and toxicity together on a two-dimensional matrix provides a clear rendition of human safety and risk. The value of the roadmap is its capacity to chronicle the stepwise acquisition of scientific information and display it in a clear and concise fashion. Furthermore, the tiered approach and transparent display of information will contribute to greater efficiencies by calling for data only as needed (enough precision to make a decision), thus conserving animals and other resources.

  3. The wildlife/human connection: modernizing risk decisions.

    PubMed Central

    Colborn, T

    1994-01-01

    This article proposes that genetic and molecular ecotoxicology can play an important role in making policy and risk assessment decisions concerning xenobiotics. It calls for a greater awareness by ecotoxicologists to the effects in wildlife and humans resulting from transgenerational exposure to synthetic chemicals that interfere with gene expression and differentiation. The difficulty of recognizing these effects on the endocrine, immune, and nervous systems in developing embryos is described and suggests why effects of this nature have traditionally not been addressed when determining risk to synthetic chemicals. Specific examples are cited of environmental effects on hormonally responsive tissue in wildlife populations which could be used as models for assessing human exposure to synthetic chemicals. Evidence is presented that the environmental load of synthetic chemicals has reached critical levels at which wildlife and human health are at risk. PMID:7713035

  4. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

    Hasanjani Roushan, Mohammad Reza; Moulana, Zahra; Afshar, Zeinab Mohseni; Ebrahimpour, Soheil

    2016-01-01

    Background & Propose: Brucellosis is serious disease around the world, especially in underdeveloped countries. Relapse is major problem in therapy of brucellosis. This study aimed to evaluate risk factors of relapse after treatment in patients. Methods: It is a descriptive-analytic study from 1990 to 2014, in Ayatolla Rohani hospital in Babol, Iran. We studied 980 patients with brucellosis. The studied community included patients infected with brucellosis and the required information was gathered based on their hospital files. The base for recognizing Malta fever were clinical symptoms and Para-clinical sign congruent with infection like as, titer SAT>1:320 and 2-ME>1:160. Patients with relapse and patients without relapse were placed separately in two groups. The data were statistically compared with Spss 16, by Chi-square and Cox–regression tests. Results: Based on this study, treatment regimen is a preventive factor (P=0.000). Moreover, Based on some statistical methods, regimens no. 3 and 4 were introduce preventive factors (P=0.001) and (P=0.004). It should also be noted that findings the same statistical model, factors like gender, age, residence, professional contacts, complications and delay in treatment were also analyzed but none of them are considered as preventive factors. Conclusion: Based our finding, we suggest aminoglycosides (gentamicin or streptomycin with doxycycline) are associated with lower rate of relapse in brucellosis. PMID:26925907

  5. TANK S-109 LONG TERM HUMAN HEALTH RISK CALCULATIONS

    SciTech Connect

    CARLSON, S.E.

    2003-12-16

    This document provides Tank S-109 long-term human risks calculations, in support of Functions and Requirements document (RPP-18812) as required by milestone M-45-00 of the Hanford Federal Facility Agreement and Consent Order. This calculation was performed to provide a screening-level assessment of long-term human health risk associated with potential leakage that could occur during waste retrieval operations for tank S-109 This calculation supports the development of tank S-109 waste retrieval functions and requirements as documented in RPP-18812. Risks associated with current waste and potential residual waste in tank S-109, as well as risk associated with other S farm tanks, were not of interest and were not evaluated.

  6. Career and Technical Education Reforms and Comprehensive School Reforms in High Schools: Their Impact on Education Outcomes for At-Risk Youth. The Highlight Zone: Research @ Work.

    ERIC Educational Resources Information Center

    Castellano, Marisa; Stringfield, Samuel; Stone, James R., III

    The impact of career and technical education (CTE) reforms and comprehensive school reforms in high schools on education outcomes for at-risk youth was examined in a review of research on current reforms. The review identified a series of individual, family and home, school, and community factors that can place students at risk of failing to…

  7. The Effects of a Computer Assisted Reading Program on the Oral Reading Fluency and Comprehension of At-Risk, Urban First Grade Students

    ERIC Educational Resources Information Center

    Gibson, Lenwood, Jr.

    2009-01-01

    The current investigation studied the effects of a computer software program of the oral reading fluency and comprehension of eight, first grade students. These students were identified as being either "at-risk" or "some-risk" for reading failure on the DIBELS oral reading fluency winter benchmark assessment. A multiple probe…

  8. Monograph: reassessment of human cancer risk of aldrin/dieldrin.

    PubMed

    Stevenson, D E; Walborg, E F; North, D W; Sielken, R L; Ross, C E; Wright, A S; Xu, Y; Kamendulis, L M; Klaunig, J E

    1999-10-05

    In 1987, the US Environmental Protection Agency (EPA) classified aldrin and dieldrin as category B2 carcinogens, i.e. probable human carcinogens, based largely on the increase in liver tumors in mice fed either organochlorine insecticide. At that date, the relevant epidemiology was deemed inadequate to influence the cancer risk assessment. More time has now elapsed since early exposures of manufacturing workers to aldrin/dieldrin; therefore, updated epidemiological data possess more power to detect exposure-related differences in cancer risk and mortality. Also, recent experimental studies provide a plausible mode of action to explain the mouse specificity of dieldrin-induced hepatocarcinogenesis and call into question the relevance of this activity to human cancer risk. This monograph places this new information within the historic and current perspectives of human cancer risk assessment, including EPA's 1996 Proposed Guidelines for Carcinogen Risk Assessment. Updated epidemiological studies of manufacturing workers in which lifetime exposures to aldrin/dieldrin have been quantified do not indicate increased mortality or cancer risk. In fact, at the middle range of exposures, there is evidence of a decrease in both mortality from all causes and cancer. Recent experimental studies indicate that dieldrin-induced hepatocarcinogenesis in mice occurs through a nongenotoxic mode of action, in which the slow oxidative metabolism of dieldrin is accompanied by an increased production of reactive oxygen species, depletion of hepatic antioxidant defenses (particularly alpha-tocopherol), and peroxidation of liver lipids. Dieldrin-induced oxidative stress or its sequelae apparently result in modulation of gene expression that favors expansion of initiated mouse, but not rat, liver cells; thus, dieldrin acts as a nongenotoxic promoter/accelerator of background liver tumorigenesis in the mouse. Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it

  9. A Third-Generation Evidence Base for Human Spaceflight Risks

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.; Lumpkins, Sarah; Steil, Jennifer; Pellis, Neal; Charles, John

    2014-01-01

    NASA's Human Research Program seeks to understand and mitigate risks to crew health and performance in exploration missions center dot HRP's evidence base consists of an Evidence Report for each HRP risk center dot Three generations of Evidence Reports 1) Review articles + Good content - Limited authorship, infrequent updates 2) Wikipedia articles + Viewed often, very open to contributions - Summary of reviews, very few contributions 3) HRP-controlled wiki articles + Incremental additions to review articles with editorial control

  10. Human monitoring of phthalates and risk assessment.

    PubMed

    Koo, Hyun Jung; Lee, Byung Mu

    2005-08-27

    Some phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), and their metabolites are suspected of producing teratogenic and endocrino-disrupting effects. In this study, urinary levels of phthalates (DEHP, DBP, diethyl phthalate (DEP), butylbenzyl phthalate BBP), and monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) were measured by high performance liquid chromatography (HPLC) in human populations (women [hospital visitors], n = 150, and children, n = 150). Daily exposure level of DEHP in children was estimated to be 12.4 microg/kg body weight/d (male 9.9 microg/kg body weight/d, female 17.8 microg/kg body weight/d), but, in women was estimated to be 41.7 microg/kg body weight/d, which exceeded the tolerable daily intake (TDI, 37 microg/kg body weight/day) level established by the European Union (EU) Scientific Committee for Toxicity, Ecotoxicity, and the Environment (SCTEE) based on reproductive toxicity. Based on these data, hazard indices (HIs) were calculated to be 1.12 (41.7/37 TDI) for women and 0.33 (12.4/37 TDI) for children, respectively. These data suggest that Koreans (women and children) were exposed to significant levels of phthalates, which should be reduced to as low a level as technologically feasible to protect Koreans from the exposure to toxic phthalates.

  11. Nanotechnology and human health: risks and benefits.

    PubMed

    Cattaneo, Anna Giulia; Gornati, Rosalba; Sabbioni, Enrico; Chiriva-Internati, Maurizio; Cobos, Everardo; Jenkins, Marjorie R; Bernardini, Giovanni

    2010-11-01

    Nanotechnology is expected to be promising in many fields of medical applications, mainly in cancer treatment. While a large number of very attractive exploitations open up for the clinics, regulatory agencies are very careful in admitting new nanomaterials for human use because of their potential toxicity. The very active research on new nanomaterials that are potentially useful in medicine has not been counterbalanced by an adequate knowledge of their pharmacokinetics and toxicity. The different nanocarriers used to transport and release the active molecules to the target tissues should be treated as additives, with potential side effects of themselves or by virtue of their dissolution or aggregation inside the body. Only recently has a systematic classification of nanomaterials been proposed, posing the basis for dedicated modeling at the nanoscale level. The use of in silico methods, such as nano-QSAR and PSAR, while highly desirable to expedite and rationalize the following stages of toxicological research, are not an alternative, but an introduction to mandatory experimental work.

  12. Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

    PubMed Central

    Wolff, Antonio C.; Blackford, Amanda L.; Visvanathan, Kala; Rugo, Hope S.; Moy, Beverly; Goldstein, Lori J.; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S.; Theriault, Richard L.; Hughes, Melissa E.; Weeks, Jane C.; Karp, Judith E.

    2015-01-01

    Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. PMID

  13. Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

    PubMed

    Wolff, Antonio C; Blackford, Amanda L; Visvanathan, Kala; Rugo, Hope S; Moy, Beverly; Goldstein, Lori J; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S; Theriault, Richard L; Hughes, Melissa E; Weeks, Jane C; Karp, Judith E

    2015-02-01

    Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. © 2014 by American Society of Clinical Oncology.

  14. Modeling of Radiation Risks for Human Space Missions

    NASA Technical Reports Server (NTRS)

    Fletcher, Graham

    2004-01-01

    Prior to any human space flight, calculations of radiation risks are used to determine the acceptable scope of astronaut activity. Using the supercomputing facilities at NASA Ames Research Center, Ames researchers have determined the damage probabilities of DNA functional groups by space radiation. The data supercede those used in the current Monte Carlo model for risk assessment. One example is the reaction of DNA with hydroxyl radical produced by the interaction of highly energetic particles from space radiation with water molecules in the human body. This reaction is considered an important cause of DNA mutations, although its mechanism is not well understood.

  15. Modeling of Radiation Risks for Human Space Missions

    NASA Technical Reports Server (NTRS)

    Fletcher, Graham

    2004-01-01

    Prior to any human space flight, calculations of radiation risks are used to determine the acceptable scope of astronaut activity. Using the supercomputing facilities at NASA Ames Research Center, Ames researchers have determined the damage probabilities of DNA functional groups by space radiation. The data supercede those used in the current Monte Carlo model for risk assessment. One example is the reaction of DNA with hydroxyl radical produced by the interaction of highly energetic particles from space radiation with water molecules in the human body. This reaction is considered an important cause of DNA mutations, although its mechanism is not well understood.

  16. Comprehensive Population-Specific Marker Panel for Early Prostate Cancer Diagnostics and Risk Assessment

    DTIC Science & Technology

    2012-06-01

    of Green Tea Catechins in the Chemoprevention of Prostate Cancer. Nutrition and cancer. 1112011; 64(1):4-22; PMID: 22098273 2. Kumar NB, Crocker, T...Nagi Kumar. New Insights to the Mechanisms of Green Tea Catechins in the Chemoprevention ofProstate Cancer. Nutrition and cancer. 11/2011; 64(1):4-22...decreased diabetes risk and associated BMI increase; 4a and 4b ( green line): association mediated through increased BMI. Short description of the gene

  17. A spatial evaluation of global wildfire-water risks to human and natural systems.

    PubMed

    Robinne, François-Nicolas; Bladon, Kevin D; Miller, Carol; Parisien, Marc-André; Mathieu, Jérôme; Flannigan, Mike D

    2018-01-01

    The large mediatic coverage of recent massive wildfires across the world has emphasized the vulnerability of freshwater resources. The extensive hydrogeomorphic effects from a wildfire can impair the ability of watersheds to provide safe drinking water to downstream communities and high-quality water to maintain riverine ecosystem health. Safeguarding water use for human activities and ecosystems is required for sustainable development; however, no global assessment of wildfire impacts on water supply is currently available. Here, we provide the first global evaluation of wildfire risks to water security, in the form of a spatially explicit index. We adapted the Driving forces-Pressure-State-Impact-Response risk analysis framework to select a comprehensive set of indicators of fire activity and water availability, which we then aggregated to a single index of wildfire-water risk using a simple additive weighted model. Our results show that water security in many regions of the world is potentially vulnerable, regardless of socio-economic status. However, in developing countries, a critical component of the risk is the lack of socio-economic capability to respond to disasters. Our work highlights the importance of addressing wildfire-induced risks in the development of water security policies; the geographic differences in the components of the overall risk could help adapting those policies to different regional contexts. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  18. A CAMBRA Model For High Caries Risk Indian Children: A Pragmatic Comprehensive Tailored Intervention.

    PubMed

    Gauba, Krishan; Goyal, Ashima; Mittal, Neeti

    2016-01-01

    To evaluate a CAMBRA based therapeutic and preventive model for high caries risk children in a pediatric dentistry clinic set-up. A total of 100 systemically healthy children aged 4-8 years with dmft/DMFT ≥ 5 and/or ≤ 20% magnitude of cariogram sector 'chance to avoid new cavities' were enrolled. The program comprised of following components i.e. caries risk assessment, customized preventive interventions (Motivational interviewing and counseling, oral prophylaxis, fluoride varnish, fissure sealants) and restorative procedures. The recall intervals were scheduled on the basis of caries risk i.e. every 1 month (≤ 40% chance to avoid new cavities) and 3 months (≥ 41% chance to avoid new cavities). The primary outcome measure was 'new carious lesions' at 12 months following achievement of 'termination levels' i.e. ≥ 41% magnitude of 'chance to avoid new cavities.' The secondary outcome measures were changes in cariogram parameters at termination and duration needed to achieve termination levels. The program showed 97% success rate as 3/100 subjects developed new carious lesions at 12 months follow up. Highly significant (p<0.001) favorable shift was achieved in cariogram parameters at termination. Termination levels were achieved in 2.71 ± 4.854 months. The present CAMBRA based program with customized intervention and recall schedules showed favorable results.

  19. Defining Human Failure Events for Petroleum Risk Analysis

    SciTech Connect

    Ronald L. Boring; Knut Øien

    2014-06-01

    In this paper, an identification and description of barriers and human failure events (HFEs) for human reliability analysis (HRA) is performed. The barriers, called target systems, are identified from risk significant accident scenarios represented as defined situations of hazard and accident (DSHAs). This report serves as the foundation for further work to develop petroleum HFEs compatible with the SPAR-H method and intended for reuse in future HRAs.

  20. Tri-county comprehensive assessment of risk factors for sporadic reportable bacterial enteric infection in children

    PubMed Central

    Denno, Donna M.; Keene, William E.; Hutter, Carolyn M.; Koepsell, Jennifer K.; Patnode, Marianne; Flodin-Hursh, Denny; Stewart, Laurie K.; Duchin, Jeffrey S.; Rasmussen, Laurette; Jones, Robert; Tarr, Phillip I.

    2009-01-01

    Background. The aim of this study was to determine risk factors for childhood sporadic reportable enteric infection (REI) caused by bacteria, specifically Campylobacter, Salmonella, Escherichia coli O157, or Shigella (REI-B). Methods. Matched case-control study. Case patients aged <19 years who were reported to 3 Washington State county health departments and matched control subjects were interviewed from November 2003–November 2005. Matched odds ratios (ORs) were calculated by using conditional logistic regression. Population attributable risk percentages were calculated for exposures associated with infection. Results. Two hundred ninety-six case patients were matched to 580 control subjects. Aquatic recreation was the most important factor associated with all REI-Bs studied (beach water exposure [OR for Salmonella infection, 28.3 {CI, 7.2–112.2}; OR for Shigella infection, 14.5 {CI 1.5–141.0} or any recreational water exposure [OR for Campylobacter infection, 2.7 {CI, 1.5–4.8}; OR for Escherichia coli O157 infection, 7.4 {CI, 2.1–26.1}]). Suboptimal kitchen hygiene after preparation of raw meat or chicken (OR, 7.1 [CI, 2.1–24.1]) and consumption of food from restaurants were additional risks for Campylobacter infection. Infection with Salmonella was associated with the use of private wells as sources of drinking water (OR, 6.5 [CI, 1.4–29.7]), and the use of residential septic systems was a risk for both Salmonella (OR, 3.2 [CI, 1.3–7.8]) and E. coli (OR, 5.7 [CI, 1.2–27.2]) O157 infection. Conclusions. Overall, non-food exposures were as important as food-related exposures with regard to their contributions to the proportion of cases. Infection prevention efforts should address kitchen hygiene practices and non-food exposures, such as recreational water exposure, in addition to food-consumption risks. PMID:19281302

  1. Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers

    PubMed Central

    Li, Yiran; Li, Wan; Liang, Binhua; Li, Liansheng; Wang, Li; Huang, Hao; Guo, Shanshan; Wang, Yahui; He, Yuehan; Chen, Lina; He, Weiming

    2016-01-01

    Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The complexity of cancer can be reduced to a small number of underlying principles like cancer hallmarks which could govern the transformation of normal cells to cancer. Besides, the growth and metastasis of cancer often relate to combined effects of long non-coding RNAs (lncRNAs). Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of six types of human cancer patients from The Cancer Genome Atlas (TCGA), and identified six risk pathways and twenty three lncRNAs. In addition, twenty three cancer risk lncRNAs which were closely related to the occurrence or development of cancer had a good classification performance for samples of testing datasets of six cancer datasets. More important, these lncRNAs were able to separate samples in the entire cancer dataset into high-risk group and low-risk group with significantly different overall survival (OS), which was further validated in ten validation datasets. In our study, the robust and effective cancer biomarkers were obtained from cancer datasets which had information of normal-tumor samples. Overall, our research can provide a new perspective for the further study of clinical diagnosis and treatment of cancer. PMID:27991568

  2. Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers.

    PubMed

    Li, Yiran; Li, Wan; Liang, Binhua; Li, Liansheng; Wang, Li; Huang, Hao; Guo, Shanshan; Wang, Yahui; He, Yuehan; Chen, Lina; He, Weiming

    2016-12-19

    Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The complexity of cancer can be reduced to a small number of underlying principles like cancer hallmarks which could govern the transformation of normal cells to cancer. Besides, the growth and metastasis of cancer often relate to combined effects of long non-coding RNAs (lncRNAs). Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of six types of human cancer patients from The Cancer Genome Atlas (TCGA), and identified six risk pathways and twenty three lncRNAs. In addition, twenty three cancer risk lncRNAs which were closely related to the occurrence or development of cancer had a good classification performance for samples of testing datasets of six cancer datasets. More important, these lncRNAs were able to separate samples in the entire cancer dataset into high-risk group and low-risk group with significantly different overall survival (OS), which was further validated in ten validation datasets. In our study, the robust and effective cancer biomarkers were obtained from cancer datasets which had information of normal-tumor samples. Overall, our research can provide a new perspective for the further study of clinical diagnosis and treatment of cancer.

  3. Lower-Risk Cannabis Use Guidelines: A Comprehensive Update of Evidence and Recommendations.

    PubMed

    Fischer, Benedikt; Russell, Cayley; Sabioni, Pamela; van den Brink, Wim; Le Foll, Bernard; Hall, Wayne; Rehm, Jürgen; Room, Robin

    2017-08-01

    Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health outcomes. Cannabis control regimes are evolving, for example toward a national legalization policy in Canada, with the aim to improve public health, and thus require evidence-based interventions. As cannabis-related health outcomes may be influenced by behaviors that are modifiable by the user, evidence-based Lower-Risk Cannabis Use Guidelines (LRCUG)-akin to similar guidelines in other health fields-offer a valuable, targeted prevention tool to improve public health outcomes. To systematically review, update, and quality-grade evidence on behavioral factors determining adverse health outcomes from cannabis that may be modifiable by the user, and translate this evidence into revised LRCUG as a public health intervention tool based on an expert consensus process. We used pertinent medical search terms and structured search strategies, to search MEDLINE, EMBASE, PsycINFO, Cochrane Library databases, and reference lists primarily for systematic reviews and meta-analyses, and additional evidence on modifiable risk factors for adverse health outcomes from cannabis use. We included studies if they focused on potentially modifiable behavior-based factors for risks or harms for health from cannabis use, and excluded studies if cannabis use was assessed for therapeutic purposes. We screened the titles and abstracts of all studies identified by the search strategy and assessed the full texts of all potentially eligible studies for inclusion; 2 of the authors independently extracted the data of all studies included in this review. We created Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow-charts for each of the topical searches. Subsequently, we summarized the evidence by behavioral factor topic, quality-graded it by following standard (Grading of Recommendations Assessment, Development, and Evaluation; GRADE

  4. Comprehensive meta-analytical summary on human papillomavirus association with head and neck cancer.

    PubMed

    Bychkov, V A; Nikitina, E G; Ibragimova, M K; Kaigorodova, E V; Choinzonov, E L; Litviakov, N V

    2016-06-01

    An etiological role of high risk human papillomavirus (HPV) in the development of cervical cancer has been well established. Hence, attention of researchers has been focused on the role of HPV in pathogenesis of other malignancies, such as head and neck cancers. An analysis of epidemiological data on the prevalence of HPV infection among healthy people and patients with precancerous lesions and/or cancer is an important step in understanding the role of HPV in head and neck carcinogenesis. More and more data de-monstrate the impact of HPV infection on disease outcome. HPV-positive patients have been shown to have better responses to radiotherapy and better overall and disease-free survival than HPV-negative patients. This review presents data of the meta-analysis based on a large number of original studies on HPV prevalence in patients with precancerous lesions and in patients with oral, oropharyngeal and laryngeal cancers as well as findings on the impact of HPV infection on survival of these patients.

  5. Interventions to Address Medical Conditions and Health-Risk Behaviors Among Persons With Serious Mental Illness: A Comprehensive Review

    PubMed Central

    McGinty, Emma E.; Baller, Julia; Azrin, Susan T.; Juliano-Bult, Denise; Daumit, Gail L.

    2016-01-01

    People with serious mental illness (SMI) have mortality rates 2 to 3 times higher than the overall US population, largely due to cardiovascular disease. The prevalence of cardiovascular risk factors such as obesity and diabetes mellitus and other conditions, such as HIV/AIDS, is heightened in this group. Based on the recommendations of a National Institute of Mental Health stakeholder meeting, we conducted a comprehensive review examining the strength of the evidence surrounding interventions to address major medical conditions and health-risk behaviors among persons with SMI. Peer-reviewed studies were identified using 4 major research databases. Randomized controlled trials and observational studies testing interventions to address medical conditions and risk behaviors among persons with schizophrenia and bipolar disorder between January 2000 and June 2014 were included. Information was abstracted from each study by 2 trained reviewers, who also rated study quality using a standard tool. Following individual study review, the quality of the evidence (high, medium, low) and the effectiveness of various interventions were synthesized. 108 studies were included. The majority of studies examined interventions to address overweight/obesity (n = 80). The strength of the evidence was high for 4 interventions: metformin and behavioral interventions had beneficial effects on weight loss; and bupropion and varenicline reduced tobacco smoking. The strength of the evidence was low for most other interventions reviewed. Future studies should test long-term interventions to cardiovascular risk factors and health-risk behaviors. In addition, future research should study implementation strategies to effectively translate efficacious interventions into real-world settings. PMID:26221050

  6. Interventions to Address Medical Conditions and Health-Risk Behaviors Among Persons With Serious Mental Illness: A Comprehensive Review.

    PubMed

    McGinty, Emma E; Baller, Julia; Azrin, Susan T; Juliano-Bult, Denise; Daumit, Gail L

    2016-01-01

    People with serious mental illness (SMI) have mortality rates 2 to 3 times higher than the overall US population, largely due to cardiovascular disease. The prevalence of cardiovascular risk factors such as obesity and diabetes mellitus and other conditions, such as HIV/AIDS, is heightened in this group. Based on the recommendations of a National Institute of Mental Health stakeholder meeting, we conducted a comprehensive review examining the strength of the evidence surrounding interventions to address major medical conditions and health-risk behaviors among persons with SMI. Peer-reviewed studies were identified using 4 major research databases. Randomized controlled trials and observational studies testing interventions to address medical conditions and risk behaviors among persons with schizophrenia and bipolar disorder between January 2000 and June 2014 were included. Information was abstracted from each study by 2 trained reviewers, who also rated study quality using a standard tool. Following individual study review, the quality of the evidence (high, medium, low) and the effectiveness of various interventions were synthesized. 108 studies were included. The majority of studies examined interventions to address overweight/obesity (n = 80). The strength of the evidence was high for 4 interventions: metformin and behavioral interventions had beneficial effects on weight loss; and bupropion and varenicline reduced tobacco smoking. The strength of the evidence was low for most other interventions reviewed. Future studies should test long-term interventions to cardiovascular risk factors and health-risk behaviors. In addition, future research should study implementation strategies to effectively translate efficacious interventions into real-world settings. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Human Health Risk Assessment of Trichloroethylene from Industrial Complex A

    PubMed Central

    Sin, Saemi

    2012-01-01

    This study investigated the human health risks of trichloroethylene from Industrial Complex A. The excessive carcinogenic risks for central tendency exposure were 1.40 × 10?5 for male and female residents in the vicinity of Industrial Complex A. The excessive cancers risk for reasonable maximum exposure were 2.88 × 10?5 and 1.97 × 10?5 for males and females, respectively. These values indicate that there are potential cancer risks for exposure to these concentrations. The hazard index for central tendency exposure to trichloroethylene was 1.71 for male and female residents. The hazard indexes for reasonable maximum exposure were 3.27 and 2.41 for males and females, respectively. These values were over one, which is equivalent to the threshold value. This result showed that adverse cancer and non-cancer health effects may occur and that some risk management of trichloroethylene from Industrial Complex A was needed. PMID:24278607

  8. Children's exposure to harmful elements in toys and low-cost jewelry: characterizing risks and developing a comprehensive approach.

    PubMed

    Guney, Mert; Zagury, Gerald J

    2014-04-30

    Contamination problem in jewelry and toys and children's exposure possibility have been previously demonstrated. For this study, risk from oral exposure has been characterized for highly contaminated metallic toys and jewelry ((MJ), n=16) considering three scenarios. Total and bioaccessible concentrations of Cd, Cu, Ni, and Pb were high in selected MJ. First scenario (ingestion of parts or pieces) caused unacceptable risk for eight items for Cd, Ni, and/or Pb (hazard index (HI)>1, up to 75, 5.8, and 43, respectively). HI for ingestion of scraped-off material scenario was always <1. Finally, saliva mobilization scenario caused HI>1 in three samples (two for Cd, one for Ni). Risk characterization identified different potentially hazardous items compared to United States, Canadian, and European Union approaches. A comprehensive approach was also developed to deal with complexity and drawbacks caused by various toy/jewelry definitions, test methods, exposure scenarios, and elements considered in different regulatory approaches. It includes bioaccessible limits for eight priority elements (As, Cd, Cr, Cu, Hg, Ni, Pb, and Sb). Research is recommended on metals bioaccessibility determination in toys/jewelry, in vitro bioaccessibility test development, estimation of material ingestion rates and frequency, presence of hexavalent Cr and organic Sn, and assessment of prolonged exposure to MJ. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Validation of the Subjective Numeracy Scale: effects of low numeracy on comprehension of risk communications and utility elicitations.

    PubMed

    Zikmund-Fisher, Brian J; Smith, Dylan M; Ubel, Peter A; Fagerlin, Angela

    2007-01-01

    In a companion article, the authors describe the Subjective Numeracy Scale (SNS), a self-assessment of numerical aptitude and preferences for numbers that correlates strongly with objective numeracy. The objective of this article is to validate the Subjective Numeracy Scale using measures of subjects' capacity to recall and comprehend complex risk statistics and to complete utility elicitations. The study is composed of 3 general public surveys: 2 administered via the Web and 1 by paper and pencil. Subjects. Studies 1 and 3 surveyed 862 and 1234 people, respectively, recruited via a nationwide commercial Internet survey panel. Study 2 involved 245 people who completed paper-and-pencil surveys in a Veterans Administration hospital. The authors tested whether one's score on the SNS predicted the likelihood of correct recall and interpretation of risk information (studies 1 and 2A) or the likelihood of effectively completing a time tradeoff or person-tradeoff utility elicitation (studies 2B and 3). In Studies 1 and 2, the authors also tested whether an objective test of quantitative ability would predict performance. In all studies, survey participants with higher SNS scores performed significantly better than other respondents. The predictive ability of the SNS approached that observed for objective numeracy. The SNS effectively predicts both risk comprehension and completion of utility elicitations without requiring survey participants to complete time-consuming and stress-inducing mathematics tests. The authors encourage the use of the SNS in a variety of health services research contexts.

  10. Statistical aspects and risks of human-caused earthquakes

    NASA Astrophysics Data System (ADS)

    Klose, C. D.

    2013-12-01

    The seismological community invests ample human capital and financial resources to research and predict risks associated with earthquakes. Industries such as the insurance and re-insurance sector are equally interested in using probabilistic risk models developed by the scientific community to transfer risks. These models are used to predict expected losses due to naturally occurring earthquakes. But what about the risks associated with human-caused earthquakes? Such risk models are largely absent from both industry and academic discourse. In countries around the world, informed citizens are becoming increasingly aware and concerned that this economic bias is not sustainable for long-term economic growth, environmental and human security. Ultimately, citizens look to their government officials to hold industry accountable. In the Netherlands, for example, the hydrocarbon industry is held accountable for causing earthquakes near Groningen. In Switzerland, geothermal power plants were shut down or suspended because they caused earthquakes in canton Basel and St. Gallen. The public and the private non-extractive industry needs access to information about earthquake risks in connection with sub/urban geoengineeing activities, including natural gas production through fracking, geothermal energy production, carbon sequestration, mining and water irrigation. This presentation illuminates statistical aspects of human-caused earthquakes with respect to different geologic environments. Statistical findings are based on the first catalog of human-caused earthquakes (in Klose 2013). Findings are discussed which include the odds to die during a medium-size earthquake that is set off by geomechanical pollution. Any kind of geoengineering activity causes this type of pollution and increases the likelihood of triggering nearby faults to rupture.

  11. Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection.

    PubMed

    Njeru, J; Wareth, G; Melzer, F; Henning, K; Pletz, M W; Heller, R; Neubauer, H

    2016-08-22

    Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease

  12. A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk

    PubMed Central

    Li, Wei; Liu, Dahai; He, Kan

    2016-01-01

    Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC. We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ2-based Q statistic test Begg's funnel plot or Egger's test, respectively. Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106-1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results. PMID:27661122

  13. [Prevalence and risk factors for sickle retinopathy in a sub-Saharan comprehensive Sickle Cell Center].

    PubMed

    Dembélé, A K; Toure, B A; Sarro, Y S; Guindo, A; Fané, B; Offredo, L; Kené, S; Conaré, I; Tessougué, O; Traoré, Y; Badiaga, Y; Sidibé, M B; Diabaté, D; Coulibaly, M; Kanta, M; Ranque, B; Diallo, D A

    2017-09-01

    Retinopathy is a chronic complication with severe functional consequences in patients with sickle cell disease. Its prevalence is not well known in sub-Saharan Africa because of the absence of screening. We report here the results of a routine screening for sickle retinopathy in a Comprehensive Sickle Cell Center in Sub-Saharan Africa. Screening of sickle retinopathy was carried out in all sickle cell patients aged 10 and over, followed between 2010 and 2012. Retinopathy was screened by dilated indirect fundoscopic examination and retinal angiography, if necessary. The gender, age and hematological parameters of patients with sickle retinopathy were compared with those of controls randomly selected from the cohort of sickle cell patients without retinopathy followed during the same period. The overall prevalence of sickle cell retinopathy was 8.8% (142/1604): 12.4% (91/731) in SC, 5.2% (38/734) in SS, 9.4% (5/53) in Sβ°-thalassemia patients and 9.3% (8/86) in Sβ(+)-thalassemia patients. Proliferative retinopathy was more common in SC patients (P<0.01). High levels of hemoglobin or of hematocrit were associated with retinopathy in all patients and with proliferative retinopathy in SC patients. In SS or Sβ(0)thalassemia patients, high leukocyte count was associated with proliferative retinopathy. Low fetal hemoglobin level was associated with retinopathy in all groups. The prevalence of sickle cell retinopathy is high and negatively associated to the level of fetal hemoglobin. The efficiency of a routine screening for sickle cell retinopathy must be assessed in Africa as well as the benefit of phlebotomy and hydroxyurea therapy as a preventive treatments. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. Meniscal Transplantation and its Effect on Osteoarthritis Risk: an abridged protocol for the MeTEOR study: a comprehensive cohort study incorporating a pilot randomised controlled trial.

    PubMed

    Smith, N A; Achten, J; Parsons, N; Wright, D; Parkinson, B; Thompson, P; Hutchinson, C E; Spalding, T; Costa, M L

    2015-06-01

    Subtotal or total meniscectomy in the medial or lateral compartment of the knee results in a high risk of future osteoarthritis. Meniscal allograft transplantation has been performed for over thirty years with the scientifically plausible hypothesis that it functions in a similar way to a native meniscus. It is thought that a meniscal allograft transplant has a chondroprotective effect, reducing symptoms and the long-term risk of osteoarthritis. However, this hypothesis has never been tested in a high-quality study on human participants. This study aims to address this shortfall by performing a pilot randomised controlled trial within the context of a comprehensive cohort study design. Patients will be randomised to receive either meniscal transplant or a non-operative, personalised knee therapy program. MRIs will be performed every four months for one year. The primary endpoint is the mean change in cartilage volume in the weight-bearing area of the knee at one year post intervention. Secondary outcome measures include the mean change in cartilage thickness, T2 maps, patient-reported outcome measures, health economics assessment and complications. This study is expected to report its findings in 2016. Cite this article: Bone Joint Res 2015;4:93-8. ©2015 The British Editorial Society of Bone & Joint Surgery.

  15. Countries at Risk: Heightened Human Security Risk to States With Transboundary Water Resources and Instability

    NASA Astrophysics Data System (ADS)

    Veilleux, J. C.; Sullivan, G. S.; Paola, C.; Starget, A.; Watson, J. E.; Hwang, Y. J.; Picucci, J. A.; Choi, C. S.

    2014-12-01

    The Countries at Risk project is a global assessment of countries with transboundary water resources that are at risk for conflict because of high human security instability. Building upon Basins at Risk (BAR) research, our team used updated Transboundary Freshwater Dispute Database georeferenced social and environmental data, quantitative data from global indices, and qualitative data from news media sources. Our assessment considered a combination of analyzing 15 global indices related to water or human security to identify which countries scored as highest risk in each index. From this information, we were able to assess the highest risk countries' human security risk by using a new human security measurement tool, as well as comparing this analysis to the World Bank's Fragile States Index and the experimental Human Security Index. In addition, we identified which countries have the highest number of shared basins, the highest percentage of territory covered by a transboundary basin, and the highest dependency of withdrawal from transboundary waters from outside their country boundaries. By synthesizing these social and environmental data assessments, we identified five countries to analyze as case studies. These five countries are Afghanistan, China, Iraq, Moldova, and Sudan. We created a series of 30 maps to spatial analyze the relationship between the transboundary basins and social and environmental parameters to include population, institutional capacity, and physical geography by country. Finally, we synthesized our spatial analysis, Human Security Key scores, and current events scored by using the BAR scale to determine what aspects and which basins are most at risk with each country in our case studies and how this concerns future global water resources.

  16. THE POLITICS OF RISK AND EU GOVERNANCE OF HUMAN MATERIAL.

    PubMed

    Farrel, Anne-Maree

    2009-03-01

    This paper examines the politics of EU risk governance in relation to human material. It is argued that the political context has informed the way in which risks in relation to various types of human material have come to be defined as policy problems at EU level. In turn, this has influenced the design and/or persistence of institutional arrangements to manage such problems. It is further argued that this political context has resulted in a significant level of disconnection in risk governance in the area. This has happened in two ways. First, there has been a growing level of disconnection between institutional and stakeholder demands for a more expansive approach to risk governance in the area and the narrowly-circumscribed competence under Article 152(4)(a) EC, which permits the adoption of risk regulation regimes that set minimum standards of quality and safety in relation to blood, tissue/cells and organs. Second, it has led to the development of institutional arrangements that promote a bifurcated approach to risk governance, specifically in relation to blood and tissues/cells. Although a hybrid of traditional and new governance mechanisms have been employed to address this problem of disconnection, this has nevertheless added a further layer to already complex institutional arrangements for risk governance in the area. It is suggested that a more integrated approach to EU risk governance in relation to human material is needed. Implementing such an approach would contribute to greater clarity, transparency and accountability in decision-making processes, and this could enhance public trust in what is a politically-sensitive area of governance at EU level.

  17. THE POLITICS OF RISK AND EU GOVERNANCE OF HUMAN MATERIAL

    PubMed Central

    Farrel, Anne-Maree

    2012-01-01

    This paper examines the politics of EU risk governance in relation to human material. It is argued that the political context has informed the way in which risks in relation to various types of human material have come to be defined as policy problems at EU level. In turn, this has influenced the design and/or persistence of institutional arrangements to manage such problems. It is further argued that this political context has resulted in a significant level of disconnection in risk governance in the area. This has happened in two ways. First, there has been a growing level of disconnection between institutional and stakeholder demands for a more expansive approach to risk governance in the area and the narrowly-circumscribed competence under Article 152(4)(a) EC, which permits the adoption of risk regulation regimes that set minimum standards of quality and safety in relation to blood, tissue/cells and organs. Second, it has led to the development of institutional arrangements that promote a bifurcated approach to risk governance, specifically in relation to blood and tissues/cells. Although a hybrid of traditional and new governance mechanisms have been employed to address this problem of disconnection, this has nevertheless added a further layer to already complex institutional arrangements for risk governance in the area. It is suggested that a more integrated approach to EU risk governance in relation to human material is needed. Implementing such an approach would contribute to greater clarity, transparency and accountability in decision-making processes, and this could enhance public trust in what is a politically-sensitive area of governance at EU level. PMID:23326180

  18. Gender Differences in Individuals at High-Risk of Psychosis: A Comprehensive Literature Review

    PubMed Central

    Barajas, Ana; Ochoa, Susana; Obiols, Jordi E.; Lalucat-Jo, Lluís

    2015-01-01

    Introduction. To date, few studies have focused on the characterization of clinical phenomenology regarding gender in population at high-risk of psychosis. This paper is an attempt to summarize the findings found in the scientific literature regarding gender differences in high-risk populations, taking into account parameters studied in populations with schizophrenia and other psychotic disorders, such as incidence, clinical expression, duration of untreated illness (DUI), social functioning, and cognitive impairment prior to full-blown psychosis development. Method. Studies were systematically searched in PubMed. Studies using gender variable as a control variable were excluded. 12 studies met inclusion criteria. Results. Most of the studies found a differential pattern between women and men as regards clinical, social, and cognitive variables in the prodromal phase, with worse performance in men except in cognitive functioning (more severe negative symptoms, worse social functioning, and longer DUI in men). Similar conversion rates over time were found between men and women. Conclusions. Many of the studies analyzed suggest that differences between men and women in the expression of psychosis extend across a continuum, from the subclinical forms of illness to the debut of psychosis. However, the small number of studies and their significant methodological and clinical limitations do not allow for firm conclusions. PMID:25685840

  19. Preoperative evaluation and comprehensive risk assessment for children with Down syndrome.

    PubMed

    Lewanda, Amy Feldman; Matisoff, Andrew; Revenis, Mary; Harahsheh, Ashraf; Futterman, Craig; Nino, Gustavo; Greenberg, Jay; Myseros, John S; Rosenbaum, Kenneth N; Summar, Marshall

    2016-04-01

    Down syndrome is a common chromosome disorder affecting all body systems. This creates unique physiologic concerns that can affect safety during anesthesia and surgery. Little consensus exists, however, on the best way to evaluate children with Down syndrome in preparation for surgery. We review a number of salient topics affecting these children in the perioperative period, including cervical spine instability, cardiovascular abnormalities, pulmonary hypertension, upper airway obstruction, hematologic disturbances, prematurity, low birth weight, and the use of supplements and alternative therapies. Recommendations include obtaining a complete blood count to detect an increased risk for bleeding or stroke, and cardiology evaluation to identify patients with pulmonary hypertension, as well as undiagnosed or residual heart disease. Pediatric cardiac anesthesiologists and intensivists should be involved as needed. The potential for cervical spine instability should be considered, and the anesthesiologist may wish to have several options available both for the medications and equipment used. The child's family should always be asked if he or she is on any nutritional supplements, as some products marketed to families may have secondary effects such as inhibition of platelet function. Using this evaluation in presurgical planning will allow physicians to better consider the individual circumstances for their patients with Down syndrome. Our goal was to optimize patient safety by choosing the most appropriate setting and perioperative personnel, and to mitigate those risk factors amenable to intervention. © 2016 John Wiley & Sons Ltd.

  20. Promoting organizational well-being: a comprehensive review of Trauma Risk Management.

    PubMed

    Whybrow, D; Jones, N; Greenberg, N

    2015-06-01

    Trauma Risk Management (TRiM) is a peer support system developed within the British Armed Forces. It aims to ensure that trauma-exposed personnel are properly supported and encouraged to seek timely help should they develop mental health problems that fail to resolve spontaneously. To summarize current knowledge about TRiM and make recommendations for further research. A search of PsychINFO, CINAHL and PubMed identified 13 published papers. TRiM outcomes were represented in different ways within the relevant studies suggesting that TRiM may have effects additional to those that it seeks to achieve. For example, a randomized controlled trial demonstrated that TRiM had a specific positive occupational effect and did no harm; a qualitative study suggested that TRiM enhanced liaison between mental health workers and line managers and a service evaluation suggested that it reduced sickness absence. In general, the process appears to enhance trauma-exposed personnel's reliance on peer support and TRiM was reportedly acceptable and sustainable. Evidence suggests that TRiM's utility has moved beyond the military to other organizations where personnel risk occupational traumatic exposure. Further research would help to understand how TRiM is perceived by line managers and how it functions within the trauma-prone populations. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Risk-adjusting hospital mortality using a comprehensive electronic record in an integrated health care delivery system.

    PubMed

    Escobar, Gabriel J; Gardner, Marla N; Greene, John D; Draper, David; Kipnis, Patricia

    2013-05-01

    Using a comprehensive inpatient electronic medical record, we sought to develop a risk-adjustment methodology applicable to all hospitalized patients. Further, we assessed the impact of specific data elements on model discrimination, explanatory power, calibration, integrated discrimination improvement, net reclassification improvement, performance across different hospital units, and hospital rankings. Retrospective cohort study using logistic regression with split validation. A total of 248,383 patients who experienced 391,584 hospitalizations between January 1, 2008 and August 31, 2011. Twenty-one hospitals in an integrated health care delivery system in Northern California. Inpatient and 30-day mortality rates were 3.02% and 5.09%, respectively. In the validation dataset, the greatest improvement in discrimination (increase in c statistic) occurred with the introduction of laboratory data; however, subsequent addition of vital signs and end-of-life care directive data had significant effects on integrated discrimination improvement, net reclassification improvement, and hospital rankings. Use of longitudinally captured comorbidities did not improve model performance when compared with present-on-admission coding. Our final model for inpatient mortality, which included laboratory test results, vital signs, and care directives, had a c statistic of 0.883 and a pseudo-R of 0.295. Results for inpatient and 30-day mortality were virtually identical. Risk-adjustment of hospital mortality using comprehensive electronic medical records is feasible and permits one to develop statistical models that better reflect actual clinician experience. In addition, such models can be used to assess hospital performance across specific subpopulations, including patients admitted to intensive care.

  2. Human risk factors associated with pilots in runway excursions.

    PubMed

    Chang, Yu-Hern; Yang, Hui-Hua; Hsiao, Yu-Jung

    2016-09-01

    A breakdown analysis of civil aviation accidents worldwide indicates that the occurrence of runway excursions represents the largest portion among all aviation occurrence categories. This study examines the human risk factors associated with pilots in runway excursions, by applying a SHELLO model to categorize the human risk factors and to evaluate the importance based on the opinions of 145 airline pilots. This study integrates aviation management level expert opinions on relative weighting and improvement-achievability in order to develop four kinds of priority risk management strategies for airline pilots to reduce runway excursions. The empirical study based on experts' evaluation suggests that the most important dimension is the liveware/pilot's core ability. From the perspective of front-line pilots, the most important risk factors are the environment, wet/containment runways, and weather issues like rain/thunderstorms. Finally, this study develops practical strategies for helping management authorities to improve major operational and managerial weaknesses so as to reduce the human risks related to runway excursions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Human and Animal Sentinels for Shared Health Risks

    PubMed Central

    Rabinowitz, Peter; Scotch, Matthew; Conti, Lisa

    2009-01-01

    Summary The tracking of sentinel health events in humans in order to detect and manage disease risks facing a larger population is a well accepted technique applied to influenza, occupational conditions, and emerging infectious diseases. Similarly, animal health professionals routinely track disease events in sentinel animal colonies and sentinel herds. The use of animals as sentinels for human health threats, or of humans as sentinels for animal disease risk, dates back at least to the era when coal miners brought caged canaries into mines to provide early warning of toxic gases. Yet the full potential of linking animal and human health information to provide warning of such “shared risks” from environmental hazards has not been realized. Reasons appear to include the professional segregation of human and animal health communities, the separation of human and animal surveillance data, and evidence gaps in the linkages between human and animal responses to environmental health hazards. The One Health initiative and growing international collaboration in response to pandemic threats, coupled with development the fields of informatics and genomics, hold promise for improved sharing of knowledge about sentinel events in order to detect and reduce environmental health threats shared between species. PMID:20148187

  4. Development of human epithelial cell systems for radiation risk assessment

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.

    1994-01-01

    The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

  5. Development of human epithelial cell systems for radiation risk assessment

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.

    1994-01-01

    The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

  6. Development of human epithelial cell systems for radiation risk assessment

    NASA Astrophysics Data System (ADS)

    Yang, C. H.; Craise, L. M.

    1994-10-01

    The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

  7. Neuropsychiatric pharmacogenetics: moving toward a comprehensive understanding of predicting risks and response.

    PubMed

    Bishop, Jeffrey R; Ellingrod, Vicki L

    2004-07-01

    Pharmacogenetic research in the area of neuropsychiatric illnesses is rapidly evolving. Due to the complexity of the human brain, it is not surprising that our knowledge about the interaction between genetics and the treatment of these illnesses is very small. The Human Genome Project (HGP) has identified > 30,000 genes; several thousand of which have been found to occur in the brain or serve a role that enhances the brain's function. Much of the research in the post-HGP era is being driven by a desire to use genetics to predict which patients deviate from the norm in terms of drug response or side effects. By identifying these people, we will be able to direct clinical practice such that therapies for these disorders can be individualized. With this in mind, the following review is intended to cover a broad understanding of CNS pharmacogenetics with the goal of summarizing available literature on promising candidate gene targets, which may eventually help us predict clinical outcomes in patients taking medications commonly used to treat neuropsychiatric disorders.

  8. Reducing the Risk of Human Missions to Mars Through Testing

    NASA Astrophysics Data System (ADS)

    Drake, Bret G.

    2007-07-01

    The NASA Deputy Administrator charted an internal NASA planning group to develop the rationale for exploration beyond low-Earth orbit. This team, termed the Exploration Blueprint, performed architecture analyses to develop roadmaps for how to accomplish the first steps beyond Low-Earth Orbit through the human exploration of Mars. Following the results of the Exploration Blueprint study, the NASA Administrator asked for a recommendation on the next steps in human and robotic exploration. Much of the focus during this period was on integrating the results from the previous studies into more concrete implementation strategies in order to understand the relationship between NASA programs, timing, and resulting budgetary implications. This resulted in an integrated approach including lunar surface operations to retire risk of human Mars missions, maximum use of common and modular systems including what was termed the exploration transfer vehicle, Earth orbit and lunar surface demonstrations of long-life systems, collaboration of human and robotic missions to vastly increase mission return, and high-efficiency transportation systems (nuclear) for deep-space transportation and power. The data provided in this summary presentation was developed to begin to address one of the key elements of the emerging implementation strategy, namely how lunar missions help retire risk of human missions to Mars. During this process the scope of the activity broadened into the issue of how testing in general, in various venues including the moon, can help reduce the risk for Mars missions.

  9. Credit scores, cardiovascular disease risk, and human capital

    PubMed Central

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E.

    2014-01-01

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

  10. Pet ownership increases human risk of encountering ticks.

    PubMed

    Jones, E H; Hinckley, A F; Hook, S A; Meek, J I; Backenson, B; Kugeler, K J; Feldman, K A

    2017-06-19

    We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products. © 2017 Blackwell Verlag GmbH.

  11. Credit scores, cardiovascular disease risk, and human capital.

    PubMed

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  12. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways.

    PubMed

    Burkhart, Julia M; Vaudel, Marc; Gambaryan, Stepan; Radau, Sonja; Walter, Ulrich; Martens, Lennart; Geiger, Jörg; Sickmann, Albert; Zahedi, René P

    2012-10-11

    Antiplatelet treatment is of fundamental importance in combatting functions/dysfunction of platelets in the pathogenesis of cardiovascular and inflammatory diseases. Dysfunction of anucleate platelets is likely to be completely attributable to alterations in posttranslational modifications and protein expression. We therefore examined the proteome of platelets highly purified from fresh blood donations, using elaborate protocols to ensure negligible contamination by leukocytes, erythrocytes, and plasma. Using quantitative mass spectrometry, we created the first comprehensive and quantitative human platelet proteome, comprising almost 4000 unique proteins, estimated copy numbers for ∼ 3700 of those, and assessed intersubject (4 donors) as well as intrasubject (3 different blood samples from 1 donor) variations of the proteome. For the first time, our data allow for a systematic and weighted appraisal of protein networks and pathways in human platelets, and indicate the feasibility of differential and comprehensive proteome analyses from small blood donations. Because 85% of the platelet proteome shows no variation between healthy donors, this study represents the starting point for disease-oriented platelet proteomics. In the near future, comprehensive and quantitative comparisons between normal and well-defined dysfunctional platelets, or between platelets obtained from donors at various stages of chronic cardiovascular and inflammatory diseases will be feasible.

  13. Flood hazard, vulnerability, and risk assessment for human life

    NASA Astrophysics Data System (ADS)

    Pan, T.; Chang, T.; Lai, J.; Hsieh, M.; Tan, Y.; Lin, Y.

    2011-12-01

    Flood risk assessment is an important issue for the countries suffering tropical cyclones and monsoon. Taiwan is located in the hot zone of typhoon tracks in the Western Pacific. There are three to five typhoons landing Taiwan every year. Typhoons and heavy rainfalls often cause inundation disaster rising with the increase of population and the development of social economy. The purpose of this study is to carry out the flood hazard, vulnerability and risk in term of human life. Based on the concept that flood risk is composed by flood hazard and vulnerability, a inundation simulation is performed to evaluate the factors of flood hazard for human life according to base flood (100-year return period). The flood depth, velocity and rising ratio are the three factors of flood hazards. Furthermore, the factors of flood vulnerability are identified in terms of human life that are classified into two main factors, residents and environment. The sub factors related to residents are the density of population and the density of vulnerable people including elders, youngers and disabled persons. The sub factors related to environment include the the number of building floors, the locations of buildings, the and distance to rescue center. The analytic hierarchy process (AHP) is adopted to determine the weights of these factors. The risk matrix is applied to show the risk from low to high based on the evaluation of flood hazards and vulnerabilities. The Tseng-Wen River watershed is selected as the case study because a serious flood was induced by Typhoon Morakot in 2009, which produced a record-breaking rainfall of 2.361mm in 48 hours in the last 50 years. The results of assessing the flood hazard, vulnerability and risk in term of human life could improve the emergency operation for flood disaster to prepare enough relief goods and materials during typhoon landing.

  14. Prevalence of High-Risk Human Papillomavirus Among Older Women

    PubMed Central

    Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.

    2009-01-01

    Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096

  15. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONH HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  16. HUMAN AND ECOLOGICAL RISK: CORRELATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  17. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONH HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  18. HUMAN AND ECOLOIGCAL RISK: CORRELATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIORNMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  19. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONG HUMAN HEALTH, ECOLOGICAL, AND ENVIRONMENTAL MONITORING

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  20. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  1. HUMAN AND ECOLOIGCAL RISK: CORRELATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIORNMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  2. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONG HUMAN HEALTH, ECOLOGICAL, AND ENVIRONMENTAL MONITORING

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  3. HUMAN AND ECOLOGICAL RISK ASSESSMENT: ASSOCIATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  4. HUMAN AND ECOLOGICAL RISK: CORRELATIONS AMONG HUMAN HEALTH, ECOLOGICAL AND ENVIRONMENTAL MONITORING DATA

    EPA Science Inventory

    While all life is affected by the quality of the environment, environmental risk factors for human and wildlife health are typically assessed using independent processes that are dissimilar in scale and scope. However, the integrated analysis of human, ecological, and environmen...

  5. The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

    PubMed

    Yamasaki, Chisato; Murakami, Katsuhiko; Fujii, Yasuyuki; Sato, Yoshiharu; Harada, Erimi; Takeda, Jun-ichi; Taniya, Takayuki; Sakate, Ryuichi; Kikugawa, Shingo; Shimada, Makoto; Tanino, Motohiko; Koyanagi, Kanako O; Barrero, Roberto A; Gough, Craig; Chun, Hong-Woo; Habara, Takuya; Hanaoka, Hideki; Hayakawa, Yosuke; Hilton, Phillip B; Kaneko, Yayoi; Kanno, Masako; Kawahara, Yoshihiro; Kawamura, Toshiyuki; Matsuya, Akihiro; Nagata, Naoki; Nishikata, Kensaku; Noda, Akiko Ogura; Nurimoto, Shin; Saichi, Naomi; Sakai, Hiroaki; Sanbonmatsu, Ryoko; Shiba, Rie; Suzuki, Mami; Takabayashi, Kazuhiko; Takahashi, Aiko; Tamura, Takuro; Tanaka, Masayuki; Tanaka, Susumu; Todokoro, Fusano; Yamaguchi, Kaori; Yamamoto, Naoyuki; Okido, Toshihisa; Mashima, Jun; Hashizume, Aki; Jin, Lihua; Lee, Kyung-Bum; Lin, Yi-Chueh; Nozaki, Asami; Sakai, Katsunaga; Tada, Masahito; Miyazaki, Satoru; Makino, Takashi; Ohyanagi, Hajime; Osato, Naoki; Tanaka, Nobuhiko; Suzuki, Yoshiyuki; Ikeo, Kazuho; Saitou, Naruya; Sugawara, Hideaki; O'Donovan, Claire; Kulikova, Tamara; Whitfield, Eleanor; Halligan, Brian; Shimoyama, Mary; Twigger, Simon; Yura, Kei; Kimura, Kouichi; Yasuda, Tomohiro; Nishikawa, Tetsuo; Akiyama, Yutaka; Motono, Chie; Mukai, Yuri; Nagasaki, Hideki; Suwa, Makiko; Horton, Paul; Kikuno, Reiko; Ohara, Osamu; Lancet, Doron; Eveno, Eric; Graudens, Esther; Imbeaud, Sandrine; Debily, Marie Anne; Hayashizaki, Yoshihide; Amid, Clara; Han, Michael; Osanger, Andreas; Endo, Toshinori; Thomas, Michael A; Hirakawa, Mika; Makalowski, Wojciech; Nakao, Mitsuteru; Kim, Nam-Soon; Yoo, Hyang-Sook; De Souza, Sandro J; Bonaldo, Maria de Fatima; Niimura, Yoshihito; Kuryshev, Vladimir; Schupp, Ingo; Wiemann, Stefan; Bellgard, Matthew; Shionyu, Masafumi; Jia, Libin; Thierry-Mieg, Danielle; Thierry-Mieg, Jean; Wagner, Lukas; Zhang, Qinghua; Go, Mitiko; Minoshima, Shinsei; Ohtsubo, Masafumi; Hanada, Kousuke; Tonellato, Peter; Isogai, Takao; Zhang, Ji; Lenhard, Boris; Kim, Sangsoo; Chen, Zhu; Hinz, Ursula; Estreicher, Anne; Nakai, Kenta; Makalowska, Izabela; Hide, Winston; Tiffin, Nicola; Wilming, Laurens; Chakraborty, Ranajit; Soares, Marcelo Bento; Chiusano, Maria Luisa; Suzuki, Yutaka; Auffray, Charles; Yamaguchi-Kabata, Yumi; Itoh, Takeshi; Hishiki, Teruyoshi; Fukuchi, Satoshi; Nishikawa, Ken; Sugano, Sumio; Nomura, Nobuo; Tateno, Yoshio; Imanishi, Tadashi; Gojobori, Takashi

    2008-01-01

    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.

  6. The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts*

    PubMed Central

    2008-01-01

    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein–protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group. PMID:18089548

  7. Addressing Human System Risks to Future Space Exploration

    NASA Technical Reports Server (NTRS)

    Paloski, W. H.; Francisco, D. R.; Davis, J. R.

    2015-01-01

    NASA is contemplating future human exploration missions to destinations beyond low Earth orbit, including the Moon, deep-space asteroids, and Mars. While we have learned much about protecting crew health and performance during orbital space flight over the past half-century, the challenges of these future missions far exceed those within our current experience base. To ensure success in these missions, we have developed a Human System Risk Board (HSRB) to identify, quantify, and develop mitigation plans for the extraordinary risks associated with each potential mission scenario. The HSRB comprises research, technology, and operations experts in medicine, physiology, psychology, human factors, radiation, toxicology, microbiology, pharmacology, and food sciences. Methods: Owing to the wide range of potential mission characteristics, we first identified the hazards to human health and performance common to all exploration missions: altered gravity, isolation/confinement, increased radiation, distance from Earth, and hostile/closed environment. Each hazard leads to a set of risks to crew health and/or performance. For example the radiation hazard leads to risks of acute radiation syndrome, central nervous system dysfunction, soft tissue degeneration, and carcinogenesis. Some of these risks (e.g., acute radiation syndrome) could affect crew health or performance during the mission, while others (e.g., carcinogenesis) would more likely affect the crewmember well after the mission ends. We next defined a set of design reference missions (DRM) that would span the range of exploration missions currently under consideration. In addition to standard (6-month) and long-duration (1-year) missions in low Earth orbit (LEO), these DRM include deep space sortie missions of 1 month duration, lunar orbital and landing missions of 1 year duration, deep space journey and asteroid landing missions of 1 year duration, and Mars orbital and landing missions of 3 years duration. We then

  8. Current status and associated human health risk of vanadium in soil in China.

    PubMed

    Yang, Jie; Teng, Yanguo; Wu, Jin; Chen, Haiyang; Wang, Guoqiang; Song, Liuting; Yue, Weifeng; Zuo, Rui; Zhai, Yuanzheng

    2017-03-01

    A detailed assessment of vanadium contamination characteristics in China was conducted based on the first national soil pollution survey. The map overlay analysis was used to evaluate the contamination level of vanadium and the non-carcinogenic risk assessment model was calculated to quantify the vanadium exposure risks to human health. The results showed that, due to the drastically increased mining and smelting activities, 26.49% of soils were contaminated by vanadium scattered in southwest of China. According to Canadian soil quality guidelines, about 8.6% of the national soil pollution survey samples were polluted, and pose high non-carcinogenic risks to the public, especially to children living in the vicinity of heavily polluted mining areas. We propose the area near the boundary of Yunnan, Guizhou, Guangxi, and Sichuan provinces as priority control areas due to their higher geochemical background or higher health risks posed to the public. Finally, recommendations for management are proposed, including minimization of contaminant inputs, establishing stringent monitoring program, using phytoremediation, and strengthening the enforcement of relevant laws. Therefore, this study provides a comprehensive assessment of soil vanadium contamination in China, and the results will provide valuable information for China's soil vanadium management and risk avoidance.

  9. Comprehensive survey of household radon gas levels and risk factors in southern Alberta

    PubMed Central

    Stanley, Fintan K.T.; Zarezadeh, Siavash; Dumais, Colin D.; Dumais, Karin; MacQueen, Renata; Clement, Fiona; Goodarzi, Aaron A.

    2017-01-01

    Background: The inhalation of naturally occurring radon (222Rn) gas from indoor air exposes lung tissue to α-particle bombardment, a highly mutagenic form of ionizing radiation that damages DNA and increases the lifetime risk of lung cancer. We analyzed household radon concentrations and risk factors in southern Alberta, including Calgary, the third-largest Canadian metropolis. Methods: A total of 2382 residential homes (2018 in Calgary and 364 in surrounding townships) from an area encompassing 82% of the southern Alberta population were tested for radon, per Health Canada guidelines, for at least 90 days (median 103 d) between 2013 and 2016. Participants also provided home metrics (construction year, build type, foundation type, and floor and room of deployment of the radon detector) via an online survey. Homes that were subsequently remediated were retested to determine the efficacy of radon reduction techniques in the region. Results: The average indoor air radon level was 126 Bq/m3, which equates to an effective absorbed radiation dose of 3.2 mSv/yr. A total of 1135 homes (47.6%) had levels of 100 Bq/m3 or higher, and 295 homes (12.4%) had levels of 200 Bq/m3 or higher; the range was less than 15 Bq/m3 to 3441 Bq/m3. Homes built in 1992 or later had radon levels 31.5% higher, on average, than older homes (mean 142 Bq/m3 v. 108 Bq/m3). For 90 homes with an average radon level of 575 Bq/m3 before mitigation, radon suppression successfully reduced levels to an average of 32.5 Bq/m3. Interpretation: Our findings show that radon exposure is a genuine public health concern in southern Alberta, suggest that modern building practices are associated with increased indoor air radon accumulation, legitimatize efforts to understand the consequences of radon exposure to the public, and suggest that radon testing and mitigation are likely to be impactful cancer prevention strategies. PMID:28401142

  10. Human Health and Environmental Risks Posed by Synthetic Biology R&D for Energy Applications: A Literature Analysis

    DOE PAGES

    Hewett, Joel P.; Wolfe, Amy K.; Bergmann, Rachael A.; ...

    2016-10-07

    What are the human health and environmental risks posed by synthetic biology research and development (R&D) for energy applications? In this study, we found it surprisingly difficult to answer this seemingly straightforward question in our review of the risk-related synthetic biology literature. To our knowledge, no entity to date has published a comprehensive review of this literature. Thus, this analysis aims to fill that void and, at a high level, answer the question that we pose. Risk-related synthetic biology literature addresses risk from different perspectives. Much of the literature that we reviewed treats the concept of risk in synthetic biologymore » R&D broadly, enumerating few specific risks. Nevertheless, after reviewing >200 documents, we identified 44 discrete risk issues; 18 of those related to human health and 26 to the environment. We clustered these risk issues into categories that reflect and summarize their content. We categorized human health risk issues as follows: allergies, antibiotic resistance, carcinogens, and pathogenicity or toxicity. Environmental risk issues were categorized as follows: change or depletion of the environment, competition with native species, horizontal gene transfer, and pathogenicity or toxicity. Our efforts to understand what the synthetic biology R&D-related risk issues are stemmed from a larger research project in which we used risk issues identified in the literature as a point of departure in interviews with biosafety professionals and scientists engaged in synthetic biology R&D. Finally, we wrote this article after multiple biosafety professionals told us that accessing our risk-related literature analysis would aid them in their work.« less

  11. Human Health and Environmental Risks Posed by Synthetic Biology R&D for Energy Applications: A Literature Analysis

    SciTech Connect

    Hewett, Joel P.; Wolfe, Amy K.; Bergmann, Rachael A.; Stelling, Savannah C.; Davis, Kimberly L.

    2016-10-07

    What are the human health and environmental risks posed by synthetic biology research and development (R&D) for energy applications? In this study, we found it surprisingly difficult to answer this seemingly straightforward question in our review of the risk-related synthetic biology literature. To our knowledge, no entity to date has published a comprehensive review of this literature. Thus, this analysis aims to fill that void and, at a high level, answer the question that we pose. Risk-related synthetic biology literature addresses risk from different perspectives. Much of the literature that we reviewed treats the concept of risk in synthetic biology R&D broadly, enumerating few specific risks. Nevertheless, after reviewing >200 documents, we identified 44 discrete risk issues; 18 of those related to human health and 26 to the environment. We clustered these risk issues into categories that reflect and summarize their content. We categorized human health risk issues as follows: allergies, antibiotic resistance, carcinogens, and pathogenicity or toxicity. Environmental risk issues were categorized as follows: change or depletion of the environment, competition with native species, horizontal gene transfer, and pathogenicity or toxicity. Our efforts to understand what the synthetic biology R&D-related risk issues are stemmed from a larger research project in which we used risk issues identified in the literature as a point of departure in interviews with biosafety professionals and scientists engaged in synthetic biology R&D. Finally, we wrote this article after multiple biosafety professionals told us that accessing our risk-related literature analysis would aid them in their work.

  12. A stress ecology framework for comprehensive risk assessment of diffuse pollution.

    PubMed

    van Straalen, Nico M; van Gestel, Cornelis A M

    2008-12-01

    Environmental pollution is traditionally classified as either localized or diffuse. Local pollution comes from a point source that emits a well-defined cocktail of chemicals, distributed in the environment in the form of a gradient around the source. Diffuse pollution comes from many sources, small and large, that cause an erratic distribution of chemicals, interacting with those from other sources into a complex mixture of low to moderate concentrations over a large area. There is no good method for ecological risk assessment of such types of pollution. We argue that effects of diffuse contamination in the field must be analysed in the wider framework of stress ecology. A multivariate approach can be applied to filter effects of contaminants from the many interacting factors at the ecosystem level. Four case studies are discussed (1) functional and structural properties of terrestrial model ecosystems, (2) physiological profiles of microbial communities, (3) detritivores in reedfield litter, and (4) benthic invertebrates in canal sediment. In each of these cases the data were analysed by multivariate statistics and associations between ecological variables and the levels of contamination were established. We argue that the stress ecology framework is an appropriate assessment instrument for discriminating effects of pollution from other anthropogenic disturbances and naturally varying factors.

  13. Good Ideas and Engagement Aren't Enough: School District Central Offices and the Micro-Politics of Implementing Comprehensive Human Resource Reform

    ERIC Educational Resources Information Center

    DeArmond, Michael

    2013-01-01

    This dissertation is about how organizational politics--or what some scholars call micro-politics--shapes the implementation of comprehensive human resource (HR) reform in school district central offices. Over the last decade, education reformers and advocates have promoted comprehensive HR reform as a way to improve teaching and learning in K-12…

  14. Good Ideas and Engagement Aren't Enough: School District Central Offices and the Micro-Politics of Implementing Comprehensive Human Resource Reform

    ERIC Educational Resources Information Center

    DeArmond, Michael

    2013-01-01

    This dissertation is about how organizational politics--or what some scholars call micro-politics--shapes the implementation of comprehensive human resource (HR) reform in school district central offices. Over the last decade, education reformers and advocates have promoted comprehensive HR reform as a way to improve teaching and learning in K-12…

  15. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

    PubMed

    Duintjer Tebbens, R J; Thompson, K M

    2017-01-01

    If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

  16. Human System Risk Management - Tools of our Trade

    NASA Technical Reports Server (NTRS)

    Ott, C. Mark

    2009-01-01

    The risk of infectious disease to select individuals has historically been difficult to predict in either spaceflight or on Earth with health care efforts relying on broad-based prevention and post-infection treatment. Over the past 10 years, quantitative microbial risk assessment evaluations have evolved to formalize the assessment process and quantify the risk. This process of hazard identification, exposure assessment, dose-response assessment, and risk characterization has been applied by the water and food safety industries to address the public health impacts associated with the occurrence of and human exposure to pathogens in water and food for the development of preventive strategies for microbial disease. NASA is currently investigating the feasibility of using these techniques to better understand the risks to astronauts and refine their microbiological requirements. To assess these techniques, NASA began an evaluation of the potable water system on the International Space Station to determine how the microbial risk from water consumption during flight differed from terrestrial sources, such as municipal water systems. The ultimate goal of this work is to optimize microbial requirements which would minimize unnecessary cargo and use of crew time, while still protecting the health of the crew. Successful demonstration of this risk assessment framework with the water system holds the potential to maximize the use of available resources during spaceflight missions and facilitate investigations into the evaluation of other routes of infection, such as through the spaceflight foods system.

  17. Human System Risk Management - Tools of our Trade

    NASA Technical Reports Server (NTRS)

    Ott, C. Mark

    2009-01-01

    The risk of infectious disease to select individuals has historically been difficult to predict in either spaceflight or on Earth with health care efforts relying on broad-based prevention and post-infection treatment. Over the past 10 years, quantitative microbial risk assessment evaluations have evolved to formalize the assessment process and quantify the risk. This process of hazard identification, exposure assessment, dose-response assessment, and risk characterization has been applied by the water and food safety industries to address the public health impacts associated with the occurrence of and human exposure to pathogens in water and food for the development of preventive strategies for microbial disease. NASA is currently investigating the feasibility of using these techniques to better understand the risks to astronauts and refine their microbiological requirements. To assess these techniques, NASA began an evaluation of the potable water system on the International Space Station to determine how the microbial risk from water consumption during flight differed from terrestrial sources, such as municipal water systems. The ultimate goal of this work is to optimize microbial requirements which would minimize unnecessary cargo and use of crew time, while still protecting the health of the crew. Successful demonstration of this risk assessment framework with the water system holds the potential to maximize the use of available resources during spaceflight missions and facilitate investigations into the evaluation of other routes of infection, such as through the spaceflight foods system.

  18. Human impacts and the global distribution of extinction risk

    PubMed Central

    Davies, Richard G; Orme, C. David L; Olson, Valerie; Thomas, Gavin H; Ross, Simon G; Ding, Tzung-Su; Rasmussen, Pamela C; Stattersfield, Ali J; Bennett, Peter M; Blackburn, Tim M; Owens, Ian P.F; Gaston, Kevin J

    2006-01-01

    Understanding the global geographical distribution of extinction risk is a key challenge in conservation biology. It remains controversial, however, to what extent areas become threat hotspots simply because of high human impacts or due to predisposing ecological conditions. Limits to the taxonomic and geographical extent, resolution and quality of previously available data have precluded a full global assessment of the relative roles of these factors. Here, we use a new global database on the geographical distributions of birds on continents and continental islands to show that, after controlling for species richness, the best predictors of the global pattern of extinction risk are measures of human impact. Ecological gradients are of secondary importance at a global scale. The converse is true for individual biogeographic realms, within which variation in human impact is reduced and its influence on extinction risk globally is therefore underestimated. These results underline the importance of a global perspective on the mechanisms driving spatial patterns of extinction risk, and the key role of anthropogenic factors in driving the current extinction crisis. PMID:16901831

  19. Human impacts and the global distribution of extinction risk.

    PubMed

    Davies, Richard G; Orme, C David L; Olson, Valerie; Thomas, Gavin H; Ross, Simon G; Ding, Tzung-Su; Rasmussen, Pamela C; Stattersfield, Ali J; Bennett, Peter M; Blackburn, Tim M; Owens, Ian P F; Gaston, Kevin J

    2006-09-07

    Understanding the global geographical distribution of extinction risk is a key challenge in conservation biology. It remains controversial, however, to what extent areas become threat hotspots simply because of high human impacts or due to predisposing ecological conditions. Limits to the taxonomic and geographical extent, resolution and quality of previously available data have precluded a full global assessment of the relative roles of these factors. Here, we use a new global database on the geographical distributions of birds on continents and continental islands to show that, after controlling for species richness, the best predictors of the global pattern of extinction risk are measures of human impact. Ecological gradients are of secondary importance at a global scale. The converse is true for individual biogeographic realms, within which variation in human impact is reduced and its influence on extinction risk globally is therefore underestimated. These results underline the importance of a global perspective on the mechanisms driving spatial patterns of extinction risk, and the key role of anthropogenic factors in driving the current extinction crisis.

  20. Trabectedin has a low cardiac risk profile: a comprehensive cardiac safety analysis.

    PubMed

    Lebedinsky, Claudia; Gómez, Javier; Park, Youn C; Nieto, Antonio; Soto-Matos, Arturo; Parekh, Trilok; Alfaro, Vicente; Roy, Elena; Lardelli, Pilar; Kahatt, Carmen

    2011-11-01

    This analysis provides a cross-study evaluation of the cardiac safety of trabectedin. Drug-related cardiac adverse events (CAEs) were retrieved from phase I-III clinical trials, pharmacovigilance databases, and spontaneously reported cases. Left ventricular ejection fraction (LVEF) was monitored in combination phase I studies with doxorubicin or pegylated liposomal doxorubicin (PLD) and in a phase III trial (with PLD). CAEs [grade 4 cardiac arrest with severe pancytopenia and sepsis (n = 1 patient), grade 4 atrial fibrillation (n = 2), and grade 1 tachycardia (n = 1)] occurred in 4/283 patients (1.4%) in 6 single-agent phase I trials. CAEs (grade 1 sinus tachycardia in a hypertensive patient and grade 1 ventricular dysfunction) occurred in 2/155 patients (1.3%) in 4 phase I combination trials. Results from 19 single-agent phase II trials showed CAEs in 20/1,132 patients (1.8%): arrhythmias (tachycardia/palpitations; n = 13; 1.1%) were the most common. A rather similar rate of symptomatic CAEs was observed in both arms of a phase III trial in recurrent ovarian cancer: 6/330 patients (1.8%; PLD) and 11/333 patients (3.3%; trabectedin/PLD). No clinically relevant LVEF changes occurred in phase I combination trials. In the phase III trial, LVEF decreases from baseline were similar: 9% of patients (PLD) and 7% (trabectedin/PLD), with no relevant symptoms. During postmarketing experience in soft tissue sarcoma (2,046 patients treated), 4 CAEs (2 cardiac arrest, 2 cardiac failure; ~0.2%) occurred in patients with preexisting conditions. Trabectedin has a low incidence of CAEs, consisting mainly of arrhythmias. This extensive data review indicates a low cardiac risk profile for trabectedin.

  1. Emergency health risk communication during the 2007 San Diego wildfires: comprehension, compliance, and recall.

    PubMed

    Sugerman, David E; Keir, Jane M; Dee, Deborah L; Lipman, Harvey; Waterman, Stephen H; Ginsberg, Michele; Fishbein, Daniel B

    2012-01-01

    In October 2007, wildfires burned nearly 300,000 acres in San Diego County, California. Emergency risk communication messages were broadcast to reduce community exposure to air pollution caused by the fires. The objective of this investigation was to determine residents' exposure to, understanding of, and compliance with these messages. From March to June 2008, the authors surveyed San Diego County residents using a 40-question instrument and random digit dialing. The 1,802 respondents sampled were predominantly 35-64 years old (65.9%), White (65.5%), and educated past high school (79.0%). Most (82.5%) lived more than 1 mile away from the fires, although many were exposed to smoky air for 5-7 days (60.7%) inside and outside their homes. Most persons surveyed reported hearing fire-related health messages (87.9%) and nearly all (97.9%) understood the messages they heard. Respondents complied with most to all of the nontechnical health messages, including staying inside the home (58.7%), avoiding outdoor exercise (88.4%), keeping windows and doors closed (75.8%), and wetting ash before cleanup (75.6%). In contrast, few (<5%) recalled hearing technical messages to place air conditioners on recirculate, use High-Efficiency Particulate Air filters, or use N-95 respirators during ash cleanup, and less than 10% of all respondents followed these specific recommendations. The authors found that nontechnical message recall, understanding, and compliance were high during the wildfires, and reported recall and compliance with technical messages were much lower. Future disaster health communication should further explore barriers to recall and compliance with technical recommendations.

  2. Combined Task and Physical Demands Analyses towards a Comprehensive Human Work Model

    DTIC Science & Technology

    2014-09-01

    the task hierarchy) that exert forces and moments on neck joints along with any head -borne mass. These low level tasks clearly overlap with the...and whole missions. The result is a comprehensive model of tasks and associated physical demands from which one can estimate the accumulative neck ...Griffon Helicopter aircrew (Pilots and Flight Engineers) reported neck pain particularly when wearing Night Vision Goggles (NVGs) (Forde et al. , 2011

  3. Chemical-induced DNA damage and human cancer risk.

    PubMed

    Poirier, Miriam C

    2012-10-01

    For more than 200 years human cancer induction has been known to be associated with a large variety of chemical exposures. Most exposures to chemical carcinogens occur as a result of occupation, pollution in the ambient environment, lifestyle choices, or pharmaceutical use. Scientific investigations have revealed that the majority of cancer causing chemicals, or chemical carcinogens, act through "genotoxic" or DNA damaging mechanisms, which involve covalent binding of the chemical to DNA (DNA adduct formation). Cancer-inducing exposures are typically frequent and/or chronic over years, and the accumulation of DNA damage or DNA adduct formation is considered to be a necessary requirement for tumor induction. Studies in animal models have indicated that the ability to reduce DNA damage will also result in reduction of tumor risk, leading to the hypothesis that individuals having the highest levels of DNA adducts may have an increased cancer risk, compared to individuals with the lowest levels of DNA adducts. Here we have reviewed twelve investigations showing 2- to 9-fold increased Relative Risks (RR) or Odds Ratios (OR) for cancer in (the 25% of) individuals having the highest DNA adduct levels, compared to (the 25% of) matched individuals with the lowest DNA adducts. These studies also provided preliminary evidence that multiple types of DNA adducts combined, or DNA adducts combined with other risk factors (such as infection or inflammation), may be associated with more than 10-fold higher cancer risks (RR = 34-60), compared to those found with a single carcinogen. Taken together the data suggest that a reduction in human DNA adduct level is likely to produce a reduction in human cancer risk.

  4. Multiplexed Quantitative Proteomics for High-Throughput Comprehensive Proteome Comparisons of Human Cell Lines.

    PubMed

    Edwards, Amanda; Haas, Wilhelm

    2016-01-01

    The proteome is the functional entity of the cell, and perturbations of a cellular system almost always cause changes in the proteome. These changes are a molecular fingerprint, allowing characterization and a greater understanding of the effect of the perturbation on the cell as a whole. Monitoring these changes has therefore given great insight into cellular responses to stress and disease states, and analytical platforms to comprehensively analyze the proteome are thus extremely important tools in biological research. Mass spectrometry has evolved as the most relevant technology to characterize proteomes in a comprehensive way. However, due to a lack of throughput capacity of mass spectrometry-based proteomics, researchers frequently use measurement of mRNA levels to approximate proteome changes. Growing evidence of substantial differences between mRNA and protein levels as well as recent improvements in mass spectrometry-based proteomics are heralding an increased use of mass spectrometry for comprehensive proteome mapping. Here we describe the use of multiplexed quantitative proteomics using isobaric labeling with tandem mass tags (TMT) for the simultaneous quantitative analysis of five cancer cell proteomes in biological duplicates in one mass spectrometry experiment.

  5. NASA's Approach to Critical Risks for Extended Human Space Flight

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark

    2014-01-01

    Planetary Robotic and Human Spaceflight Exploration Humans are exposed to a great variety of hazards in the space environment. These include the effects of weightlessness, radiation, isolation and confinement, altered day-night cycles, and others. These inherent hazards have both physiological and behavioral consequences. The adaptive capabilities of humans in these situations is remarkable, and often exceed our expectations. However, the demanding environment and challenging operational pace can push some of these adaptive processes to their limits. The NASA Human Research Program (HRP) is tasked with mitigating the most serious of these effects on human health, safety, and performance, in long-duration space flight. This can involve the development and deployment of physiological countermeasures, better understanding of the physiological alterations and avoidance of exacerbating situations, inputs to the design of future spacecraft to minimize risks, and in some cases the awareness that some level of risk might have to be accepted based on the resulting consequences and their likelihood. HRP has identified a few areas that are of special concern due to their severity, lack of understanding of underlying causes, or potential for negative impact on health or performance. Some of these areas are visual impairment possibly due to increased intracranial pressure, behavioral and performance problems due to sleep deficits and isolation, and acute and chronic effects of radiation. These problems can, if not addressed, be expected to increase on longer and more distant missions. The evidence from spaceflight, laboratory, and analog studies that supports the selection of the most critical risks will be discussed. Current and planned research programs that address these risks, and their anticipated outcomes, will also be described.

  6. Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques.

    PubMed

    He, Zhisong; Han, Dingding; Efimova, Olga; Guijarro, Patricia; Yu, Qianhui; Oleksiak, Anna; Jiang, Shasha; Anokhin, Konstantin; Velichkovsky, Boris; Grünewald, Stefan; Khaitovich, Philipp

    2017-06-01

    While human cognitive abilities are clearly unique, underlying changes in brain organization and function remain unresolved. Here we characterized the transcriptome of the cortical layers and adjacent white matter in the prefrontal cortexes of humans, chimpanzees and rhesus macaques using unsupervised sectioning followed by RNA sequencing. More than 20% of detected genes were expressed predominantly in one layer, yielding 2,320 human layer markers. While the bulk of the layer markers were conserved among species, 376 switched their expression to another layer in humans. By contrast, only 133 of such changes were detected in the chimpanzee brain, suggesting acceleration of cortical reorganization on the human evolutionary lineage. Immunohistochemistry experiments further showed that human-specific expression changes were not limited to neurons but affected a broad spectrum of cortical cell types. Thus, despite apparent histological conservation, human neocortical organization has undergone substantial changes affecting more than 5% of its transcriptome.

  7. Lower Education Level Is a Risk Factor for Peritonitis and Technique Failure but Not a Risk for Overall Mortality in Peritoneal Dialysis under Comprehensive Training System

    PubMed Central

    Kim, Hyo Jin; Lee, Joongyub; Park, Miseon; Kim, Yuri; Lee, Hajeong; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Cho, Eun Jin; Ahn, Curie

    2017-01-01

    Background Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower education level on the development of peritonitis, technique failure, and overall mortality. Methods Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (912, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression. Results A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20–65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10–2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10–3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53–2.33; P = 0.788) or intent-to-treat analysis (P = 0.726). Conclusions Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD. PMID:28056058

  8. Lower Education Level Is a Risk Factor for Peritonitis and Technique Failure but Not a Risk for Overall Mortality in Peritoneal Dialysis under Comprehensive Training System.

    PubMed

    Kim, Hyo Jin; Lee, Joongyub; Park, Miseon; Kim, Yuri; Lee, Hajeong; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Cho, Eun Jin; Ahn, Curie; Oh, Kook-Hwan

    2017-01-01

    Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower education level on the development of peritonitis, technique failure, and overall mortality. Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (912, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression. A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20-65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10-2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10-3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53-2.33; P = 0.788) or intent-to-treat analysis (P = 0.726). Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD.

  9. Comprehensive evaluation of the immune risk phenotype in successfully treated HIV-infected individuals.

    PubMed

    Ndumbi, Patricia; Gilbert, Louise; Tsoukas, Christos M

    2015-01-01

    Despite successful treatment and CD4+ T-cell recovery, HIV-infected individuals often experience a profound immune dysregulation characterized by a persistently low CD4:CD8 T-cell ratio. This residual immune dysregulation is reminiscent of the Immune Risk Phenotype (IRP) previously associated with morbidity and mortality in the uninfected elderly (>85 years). The IRP consists of laboratory markers that include: a low CD4:CD8 T-cell ratio, an expansion of CD8+CD28- T-cells and cytomegalovirus (CMV) seropositivity. Despite the significant overlap in immunological phenotypes between normal aging and HIV infection, the IRP has never been evaluated in HIV-infected individuals. In this pilot study we characterized immune changes associated with the IRP in a sample of successfully treated HIV-infected subjects. 18 virologically suppressed HIV-infected subjects were categorized into 2 groups based on their IRP status; HIV+IRP+, (n = 8) and HIV+IRP-, (n = 10) and compared to 15 age-matched HIV uninfected IRP negative controls. All individuals were assessed for functional and phenotypic immune characteristics including: pro-inflammatory cytokine production, antigen-specific proliferation capacity, replicative senescence, T-cell differentiation and lymphocyte telomere length. Compared to HIV-infected subjects without an IRP, HIV+IRP+ subjects exhibited a higher frequency of TNF-α-producing CD8+ T-cells (p = 0.05) and a reduced proportion of CD8+ naïve T-cells (p = 0.007). The IRP status was also associated with a marked up-regulation of the replicative senescence markers CD57 and KLGR1, on the surface of CD8+T-cells (p = 0.004). Finally, HIV+IRP+ individuals had a significantly shorter mean lymphocyte telomere length than their non-IRP counterparts (p = 0.03). Our findings suggest that, despite similar levels of treatment-mediated viral suppression, the phenotypic and functional immune characteristics of HIV+IRP+ individuals are distinct from those observed in non

  10. Comprehensive Evaluation of the Immune Risk Phenotype in Successfully Treated HIV-Infected Individuals

    PubMed Central

    Ndumbi, Patricia; Gilbert, Louise; Tsoukas, Christos M.

    2015-01-01

    Background Despite successful treatment and CD4+ T-cell recovery, HIV-infected individuals often experience a profound immune dysregulation characterized by a persistently low CD4:CD8 T-cell ratio. This residual immune dysregulation is reminiscent of the Immune Risk Phenotype (IRP) previously associated with morbidity and mortality in the uninfected elderly (>85 years). The IRP consists of laboratory markers that include: a low CD4:CD8 T-cell ratio, an expansion of CD8+CD28- T-cells and cytomegalovirus (CMV) seropositivity. Despite the significant overlap in immunological phenotypes between normal aging and HIV infection, the IRP has never been evaluated in HIV-infected individuals. In this pilot study we characterized immune changes associated with the IRP in a sample of successfully treated HIV-infected subjects. Methods 18 virologically suppressed HIV-infected subjects were categorized into 2 groups based on their IRP status; HIV+IRP+, (n = 8) and HIV+IRP-, (n = 10) and compared to 15 age-matched HIV uninfected IRP negative controls. All individuals were assessed for functional and phenotypic immune characteristics including: pro-inflammatory cytokine production, antigen-specific proliferation capacity, replicative senescence, T-cell differentiation and lymphocyte telomere length. Results Compared to HIV-infected subjects without an IRP, HIV+IRP+ subjects exhibited a higher frequency of TNF-α-producing CD8+ T-cells (p = 0.05) and a reduced proportion of CD8+ naïve T-cells (p = 0.007). The IRP status was also associated with a marked up-regulation of the replicative senescence markers CD57 and KLGR1, on the surface of CD8+T-cells (p = 0.004). Finally, HIV+IRP+ individuals had a significantly shorter mean lymphocyte telomere length than their non-IRP counterparts (p = 0.03). Conclusions Our findings suggest that, despite similar levels of treatment-mediated viral suppression, the phenotypic and functional immune characteristics of HIV+IRP+ individuals are

  11. Beyond human subjects: risk, ethics, and clinical development of nanomedicines.

    PubMed

    Kimmelman, Jonathan

    2012-01-01

    Clinical testing of nanomedicines presents two challenges to prevailing, human subject-centered frameworks governing research ethics. First, some nanomedical applications may present risk to persons other than research subjects. Second, pressures encountered in testing nanomedicines may present threats to the kinds of collaborations and collective activities needed for supporting clinical translation and redeeming research risk. In this article, I describe how similar challenges were encountered and addressed in gene transfer, and sketch policy options that might be explored in the nanomedicine translation arena.

  12. Interim response action basin F liquid incineration project final draft human health risk assessment. Volume 1. Final draft report

    SciTech Connect

    1991-07-01

    This document is a comprehensive, multiple exposure pathway, human health risk assessment prepared for the proposed Basin F Liquid Incineration Project. The submerged quench incinerator will treat Basin F liquid and hydrazine rinse water. The objective of the risk assessment is to establish chemical emission limits which are protective of human health. Average and maximum lifetime daily intakes were calculated for adults, children, and infants in four maximum exposure scenarios under base case and sensitivity case emissions condition. It was concluded that the incineration facility poses neither carcinogenic nor noncarcinogenic risk to any sensitive population. The assessment is divided into: (1) Incineration facility description; (2) Description of surrounding area; (3) Process of pollutant identification and selection; and (4) Determination of emission rates from incineration facility.

  13. Pesticide testing on human subjects: weighing benefits and risks.

    PubMed

    Resnik, David B; Portier, Christopher

    2005-07-01

    In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position--namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study is expected to promote human health; b) the knowledge cannot be reasonably obtained by other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and d) appropriate safeguards are in place to minimize harm to the subjects.

  14. Pesticide Testing on Human Subjects: Weighing Benefits and Risks

    PubMed Central

    Resnik, David B.; Portier, Christopher

    2005-01-01

    In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position—namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study is expected to promote human health; b) the knowledge cannot be reasonably obtained by other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and d) appropriate safeguards are in place to minimize harm to the subjects. PMID:16002367

  15. Depleted uranium human health risk assessment, Jefferson Proving Ground, Indiana

    SciTech Connect

    Ebinger, M.H.; Hansen, W.R.

    1994-04-29

    The risk to human health from fragments of depleted uranium (DU) at Jefferson Proving Ground (JPG) was estimated using two types of ecosystem pathway models. A steady-state, model of the JPG area was developed to examine the effects of DU in soils, water, and vegetation on deer that were hunted and consumed by humans. The RESRAD code was also used to estimate the effects of farming the impact area and consuming the products derived from the farm. The steady-state model showed that minimal doses to humans are expected from consumption of deer that inhabit the impact area. Median values for doses to humans range from about 1 mrem ({plus_minus}2.4) to 0.04 mrem ({plus_minus}0.13) and translate to less than 1 {times} 10{sup {minus}6} detriments (excess cancers) in the population. Monte Carlo simulation of the steady-state model was used to derive the probability distributions from which the median values were drawn. Sensitivity analyses of the steady-state model showed that the amount of DU in airborne dust and, therefore, the amount of DU on the vegetation surface, controlled the amount of DU ingested by deer and by humans. Human doses from the RESRAD estimates ranged from less than 1 mrem/y to about 6.5 mrem/y in a hunting scenario and subsistence fanning scenario, respectively. The human doses exceeded the 100 mrem/y dose limit when drinking water for the farming scenario was obtained from the on-site aquifer that was presumably contaminated with DU. The two farming scenarios were unrealistic land uses because the additional risk to humans due to unexploded ordnance in the impact area was not figured into the risk estimate. The doses estimated with RESRAD translated to less than 1 {times} 10{sup {minus}6} detriments to about 1 {times} 10{sup {minus}3} detriments. The higher risks were associated only with the farming scenario in which drinking water was obtained on-site.

  16. Understanding Flood Hazards and Vulnerabilities: New Approaches To Comprehensive Flood Risk Assessment In The U.k.

    NASA Astrophysics Data System (ADS)

    Kelman, I.; Spence, R.

    Flood risk assessment in the U.K. has traditionally considered the hazard to be princi- pally flood depth and the vulnerability to be principally damage resulting from water contact with property for a specified but arbitrary duration. Some efforts have factored in velocity and salinity at a superficial level while other research has recently exam- ined the danger of flood hazard parameters to human life. This work is valuable, but it has tended to ignore both the physical and conceptual processes which lead from flood hazards such as rainfall and sewage to a flood disaster with consequences such as property damage, casualties, and societal disruption. The work presented here uses a detailed analysis to propose a framework describing which flood vulnerabilities are susceptible to which flood hazards and how this fundamental knowledge translates into an understanding of the creation of flood risks. A flood damage scale is produced and a conceptual map of flood risk is drawn through categorising flood hazards and vulnerabilities and exploring their interaction. The physical description of flood haz- ard parameters and the parametersS potential effects form the basis for communication strategies focused on risk and vulnerability reduction.

  17. Vibrio bacteria in raw oysters: managing risks to human health.

    PubMed

    Froelich, Brett A; Noble, Rachel T

    2016-03-05

    The human-pathogenic marine bacteria Vibrio vulnificus and V. parahaemolyticus are strongly correlated with water temperature, with concentrations increasing as waters warm seasonally. Both of these bacteria can be concentrated in filter-feeding shellfish, especially oysters. Because oysters are often consumed raw, this exposes people to large doses of potentially harmful bacteria. Various models are used to predict the abundance of these bacteria in oysters, which guide shellfish harvest policy meant to reduce human health risk. Vibrio abundance and behaviour varies from site to site, suggesting that location-specific studies are needed to establish targeted risk reduction strategies. Moreover, virulence potential, rather than simple abundance, should be also be included in future modeling efforts.

  18. Vibrio bacteria in raw oysters: managing risks to human health

    PubMed Central

    Froelich, Brett A.; Noble, Rachel T.

    2016-01-01

    The human-pathogenic marine bacteria Vibrio vulnificus and V. parahaemolyticus are strongly correlated with water temperature, with concentrations increasing as waters warm seasonally. Both of these bacteria can be concentrated in filter-feeding shellfish, especially oysters. Because oysters are often consumed raw, this exposes people to large doses of potentially harmful bacteria. Various models are used to predict the abundance of these bacteria in oysters, which guide shellfish harvest policy meant to reduce human health risk. Vibrio abundance and behaviour varies from site to site, suggesting that location-specific studies are needed to establish targeted risk reduction strategies. Moreover, virulence potential, rather than simple abundance, should be also be included in future modeling efforts. PMID:26880841

  19. Minors travelling alone: a risk group for human trafficking?

    PubMed

    Derluyn, Ilse; Lippens, Valesca; Verachtert, Tony; Bruggeman, Willy; Broekaert, Eric

    2010-01-01

    Minors travelling without their parent(s) or guardian are an increasing phenomenon. Although their travel objectives might differ importantly, varying from holiday purposes to migration objectives, an important subgroup of them might be at risk to fall into exploitative circumstances, such as human trafficking. Studying the group of minors travelling alone arriving at Brussels Airport (Belgium), this research investigates the population's characteristics, the procedures used, and the risks some of these minors run of falling into exploitative situations. Firstly, registration revealed that tens of thousands minors travelling alone arrive at Brussels Airport each year, with an important part of them coming from African countries. Secondly, participant observations showed that detection of possible cases of human trafficking is a very complex issue, resulting in the alarming hypothesis that many cases of trafficking of minors travelling alone might not be detected during their journey or at their arrival at the airport.

  20. Challenges to communicate risks of human-caused earthquakes

    NASA Astrophysics Data System (ADS)

    Klose, C. D.

    2014-12-01

    The awareness of natural hazards has been up-trending in recent years. In particular, this is true for earthquakes, which increase in frequency and magnitude in regions that normally do not experience seismic activity. In fact, one of the major concerns for many communities and businesses is that humans today seem to cause earthquakes due to large-scale shale gas production, dewatering and flooding of mines and deep geothermal power production. Accordingly, without opposing any of these technologies it should be a priority of earth scientists who are researching natural hazards to communicate earthquake risks. This presentation discusses the challenges that earth scientists are facing to properly communicate earthquake risks, in light of the fact that human-caused earthquakes are an environmental change affecting only some communities and businesses. Communication channels may range from research papers, books and class room lectures to outreach events and programs, popular media events or even social media networks.

  1. Food safety in the domestic environment: the effect of consumer risk information on human disease risks.

    PubMed

    Nauta, Maarten J; Fischer, Arnout R H; van Asselt, Esther D; de Jong, Aarieke E I; Frewer, Lynn J; de Jonge, Rob

    2008-02-01

    The improvement of food safety in the domestic environment requires a transdisciplinary approach, involving interaction between both the social and natural sciences. This approach is applied in a study on risks associated with Campylobacter on broiler meat. First, some web-based information interventions were designed and tested on participant motivation and intentions to cook more safely. Based on these self-reported measures, the intervention supported by the emotion "disgust" was selected as the most promising information intervention. Its effect on microbial cross-contamination was tested by recruiting a set of participants who prepared a salad with chicken breast fillet carrying a known amount of tracer bacteria. The amount of tracer that could be recovered from the salad revealed the transfer and survival of Campylobacter and was used as a measure of hygiene. This was introduced into an existing risk model on Campylobacter in the Netherlands to assess the effect of the information intervention both at the level of exposure and the level of human disease risk. We showed that the information intervention supported by the emotion "disgust" alone had no measurable effect on the health risk. However, when a behavioral cue was embedded within the instruction for the salad preparation, the risk decreased sharply. It is shown that a transdisciplinary approach, involving research on risk perception, microbiology, and risk assessment, is successful in evaluating the efficacy of an information intervention in terms of human health risks. The approach offers a novel tool for science-based risk management in the area of food safety.

  2. Human papillomavirus in virgins and behaviour at risk.

    PubMed

    Frega, Antonio; Cenci, Maria; Stentella, Patrizia; Cipriano, Luca; De Ioris, Andrea; Alderisio, Mauro; Vecchione, Aldo

    2003-05-08

    Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

  3. Projection of human immunodeficiency virus among high-risk groups in Malaysia.

    PubMed

    Mondal, Md Nazrul Islam; Shitan, Mahendran

    2013-01-01

    Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) presents a serious healthcare threat to young individuals in Malaysia and worldwide. This study aimed to identify trends in HIV-related risk behaviors among recognized high-risk groups and to estimate HIV transmission up to the year 2015. Data and necessary information were obtained from the Ministry of Health Malaysia, published reports from the World Health Organization and United Nations Program on HIV/AIDS, and other articles. The Estimation and Projection Package was used to estimate HIV transmission. The results of the present study revealed that within the high-risk groups, intravenous drug users (IDUs) had the highest prevalence rate of HIV transmission, followed by patients with sexually transmitted infections (STIs), female sex workers (SWs), and men who have sex with men (MSM). Within these at-risk populations, patients with STIs have the highest prevalence of HIV, followed by IDUs, MSM, and SWs. If the transmission rate continues to increase, the situation will worsen; therefore, there is an urgent need for a comprehensive prevention program to control HIV transmission in Malaysia.

  4. Bioastronautics Roadmap: A Risk Reduction Strategy for Human Space Exploration

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The Bioastronautics Critical Path Roadmap is the framework used to identify and assess the risks to crews exposed to the hazardous environments of space. It guides the implementation of research strategies to prevent or reduce those risks. Although the BCPR identifies steps that must be taken to reduce the risks to health and performance that are associated with human space flight, the BCPR is not a "critical path" analysis in the strict engineering sense. The BCPR will evolve to accommodate new information and technology development and will enable NASA to conduct a formal critical path analysis in the future. As a management tool, the BCPR provides information for making informed decisions about research priorities and resource allocation. The outcome-driven nature of the BCPR makes it amenable for assessing the focus, progress and success of the Bioastronautics research and technology program. The BCPR is also a tool for communicating program priorities and progress to the research community and NASA management.

  5. THE CONCEPT OF RISK IN BIOMEDICAL RESEARCH INVOLVING HUMAN SUBJECTS

    PubMed Central

    VAN NESS, PETER H.

    2015-01-01

    An established ethical principle of biomedical research involving human subjects stipulates that risk to subjects should be proportionate to an experiment’s potential benefits. Sometimes this principle is imprecisely stated as a requirement that ‘risks and benefits’ be balanced. First, it is noted why this language is imprecise. Second, the persistence of such language is attributed to how it functions as a rhetorical trope. Finally, an argument is made that such a trope is infelicitous because it may not achieve its intended persuasive purposes. More importantly, it should be avoided because it masks the important role that chance plays in clinical research. Risk is the possibility of harm. As a precondition of harm it is unintended and undesirable in projects of biomedical research. It requires ethical vigilance. As a vehicle of chance, however, it is both intended and desirable. It requires methodological appreciation. PMID:11697390

  6. A Study of Seventh-Graders Comprehensions of Human Reproduction Concepts

    ERIC Ed