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.

    1999-11-01

    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.

  4. 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.

  5. 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.

  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. Human Research Risk Management

    NASA Video Gallery

    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...

  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. 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…

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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...

  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. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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 ...

  8. 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…

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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…

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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…

  3. 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.

  4. 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.

  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. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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)

  13. 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…

  14. 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

  15. 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…

  16. 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.

  17. 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.

  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

    2013-12-29

    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

  19. 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

  20. 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

  1. 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

  2. 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

  3. [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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. 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.

  11. 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…

  12. 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,…

  13. 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…

  14. 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…

  15. 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.

  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. 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.

  18. 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

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. Development and Implementation of a Comprehensive Risk Management Program at the USAF Academy Hospital.

    DTIC Science & Technology

    1980-04-01

    31, 1979. USAFA Hospital Regulation 161-7, Hospital Employee Health Program, Jul 14, 1978. USAFA Hospital Regulation 168-1, Patient Questionaires , Oct...Al87 344 DEVELOPMENT AND IMPLEMENTATION OF A COMPREHENSIVE RISK 1 MANAGEMENT PROGRAM AT THE USAF ACADEMY HOSPITAL(U) ARMY HEALTH CARE STUDIES AND...Baylor University In Partial Fulfillment of the Requirements for the Degree of Master of Health Administration By Captain Charles W. Boone, USAF, MSC

  4. 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.…

  5. 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.

  6. 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.

  7. 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.

  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. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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…

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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).

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  9. 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.

  10. 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.

  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 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

  13. 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.

  14. 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)

  15. 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

  16. 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…

  17. 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.

  18. 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

  19. [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

  20. 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.

  1. 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…

  2. 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…

  3. 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.

  4. 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…

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

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

    DTIC Science & Technology

    2016-04-01

    such levels creates significant but manageable risk to executing the U.S. military strategy and that further reductions would result in unacceptable...its planned force structure, we compared the Army’s risk management guidance to GAO’s risk management framework to determine if the Army’s guidance...aligned with leading practices.13 After our evaluation of the Army’s risk management guidance, we focused our review on the Army’s risk assessments

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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 ...

  19. 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.

  20. 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.

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment... availability of the chlorpyrifos registration review; preliminary human health risk assessment. This document... for the chlorpyrifos reregistration review, preliminary human health risk assessment, established...

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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...

  16. 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…

  17. 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…

  18. 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.

  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.

  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. 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

    assessment model that includes automated measurement of breast density. Scope: Assemble a cohort of women with known breast cancer risk factors and...digital mammogram files for women diagnosed with breast cancer using existing data sources and match them to controls (Harvey/Knaus). Validate and...density will translate to changes in breast cancer risk. Therefore, noise in measurement should be minimal. Thirty women were recruited under this

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

    DTIC Science & Technology

    2012-10-01

    methods (CumulusV, Volpara), developed an automated area based 15. SUBJECT TERMS Breast cancer; risk model; mammography ; breast density 16...recommendations based on an individual’s risk beginning with personalized mammography screening decisions. This will be done by increasing the ability... mammography machine vendor. Once the model is complete, tested nationally, and proven accurate, it will be available for widespread use within five to six

  3. 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

  4. 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

  5. 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.

  6. 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.

  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. 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.

  9. 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

  10. 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/.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Toxicogenomic profiling of chemically exposed humans in risk assessment

    PubMed Central

    McHale, Cliona M.; Zhang, Luoping; Hubbard, Alan E.; Smith, Martyn T.

    2010-01-01

    Gene-environment interactions contribute to complex disease development. The environmental contribution, in particular low-level and prevalent environmental exposures, may constitute much of the risk and contribute substantially to disease. Systematic risk evaluation of the majority of human chemical exposures, has not been conducted and is a goal of regulatory agencies in the U.S. and worldwide. With the recent recognition that toxicological approaches more predictive of effects in humans are required for risk assessment, in vitro human cell line data as well as animal data are being used to identify toxicity mechanisms that can be translated into biomarkers relevant to human exposure studies. In this review, we discuss how data from toxicogenomic studies of exposed human populations can inform risk assessment, by generating biomarkers of exposure, early effect, and/or susceptibility, elucidating mechanisms of action underlying exposure-related disease, and detecting response at low doses. Good experimental design incorporating precise, individual exposure measurements, phenotypic anchors (pre-disease or traditional toxicological markers), and a range of relevant exposure levels, is necessary. Further, toxicogenomic studies need to be designed with sufficient power to detect true effects of the exposure. As more studies are performed and incorporated into databases such as the Comparative Toxicogenomics Database (CTD) and Chemical Effects in Biological Systems (CEBS), data can be mined for classification of newly tested chemicals (hazard identification), and, for investigating the dose-response, inter-relationship among, genes, environment and disease in a systems biology approach (risk characterization). PMID:20382258

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  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 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. [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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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…

  13. 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.

  14. 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…

  15. 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.

  16. 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…

  17. 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

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

    DTIC Science & Technology

    2012-06-01

    valuable PCa screening and risk assessment tool. The PI has started with the genotyping of 528 DNA samples obtained from African American and European...involves extraordinary big sample size. These experiences are vital for an independent health disparity researcher. In addition, the PI obtains...1. approximately 75% of all DNA epigenetic analysis of biomarkers that can be used samples used in the PI’s supplemental project were collected

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. Comprehensively Evaluating cis-Regulatory Variation in the Human Prostate Transcriptome by Using Gene-Level Allele-Specific Expression

    PubMed Central

    Larson, Nicholas B.; McDonnell, Shannon; French, Amy J.; Fogarty, Zach; Cheville, John; Middha, Sumit; Riska, Shaun; Baheti, Saurabh; Nair, Asha A.; Wang, Liang; Schaid, Daniel J.; Thibodeau, Stephen N.

    2015-01-01

    The identification of cis-acting regulatory variation in primary tissues has the potential to elucidate the genetic basis of complex traits and further our understanding of transcriptomic diversity across cell types. Expression quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA-seq) data can improve upon the detection of cis-acting regulatory variation by leveraging allele-specific expression (ASE) patterns in association analysis. Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA-seq gene-expression data and genome-wide high-density genotypes from 471 samples of normal primary prostate tissue. Using statistical models that integrate ASE information, we identified extensive cis-eQTLs across the prostate transcriptome and found that approximately 70% of expressed genes corresponded to a significant eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were heavily concentrated near the transcription start and stop sites of affected genes, and effects were negatively correlated with distance. We identified multiple instances of cis-acting co-regulation by using phased genotype data and discovered 233 SNPs as the most strongly associated eQTLs for more than one gene. We also noted significant enrichment (25/50, p = 2E−5) of previously reported prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit of assessing ASE data in cis-eQTL analyses by showing better reproducibility of prior eQTL findings than of eQTL mapping based on total expression alone. Altogether, our analysis provides extensive functional context of thousands of SNPs in prostate tissue, and these results will be of critical value in guiding studies examining disease of the human prostate. PMID:25983244

  5. Comprehensively evaluating cis-regulatory variation in the human prostate transcriptome by using gene-level allele-specific expression.

    PubMed

    Larson, Nicholas B; McDonnell, Shannon; French, Amy J; Fogarty, Zach; Cheville, John; Middha, Sumit; Riska, Shaun; Baheti, Saurabh; Nair, Asha A; Wang, Liang; Schaid, Daniel J; Thibodeau, Stephen N

    2015-06-04

    The identification of cis-acting regulatory variation in primary tissues has the potential to elucidate the genetic basis of complex traits and further our understanding of transcriptomic diversity across cell types. Expression quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA-seq) data can improve upon the detection of cis-acting regulatory variation by leveraging allele-specific expression (ASE) patterns in association analysis. Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA-seq gene-expression data and genome-wide high-density genotypes from 471 samples of normal primary prostate tissue. Using statistical models that integrate ASE information, we identified extensive cis-eQTLs across the prostate transcriptome and found that approximately 70% of expressed genes corresponded to a significant eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were heavily concentrated near the transcription start and stop sites of affected genes, and effects were negatively correlated with distance. We identified multiple instances of cis-acting co-regulation by using phased genotype data and discovered 233 SNPs as the most strongly associated eQTLs for more than one gene. We also noted significant enrichment (25/50, p = 2E-5) of previously reported prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit of assessing ASE data in cis-eQTL analyses by showing better reproducibility of prior eQTL findings than of eQTL mapping based on total expression alone. Altogether, our analysis provides extensive functional context of thousands of SNPs in prostate tissue, and these results will be of critical value in guiding studies examining disease of the human prostate.

  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. 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.

  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 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.

  10. 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

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  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. 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. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. High risk human papillomavirus and Epstein Barr virus in human breast milk

    PubMed Central

    2012-01-01

    Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%). Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers. PMID:22937830

  19. Global Human Settlement Analysis for Disaster Risk Reduction

    NASA Astrophysics Data System (ADS)

    Pesaresi, M.; Ehrlich, D.; Ferri, S.; Florczyk, A.; Freire, S.; Haag, F.; Halkia, M.; Julea, A. M.; Kemper, T.; Soille, P.

    2015-04-01

    The Global Human Settlement Layer (GHSL) is supported by the European Commission, Joint Research Center (JRC) in the frame of his institutional research activities. Scope of GHSL is developing, testing and applying the technologies and analysis methods integrated in the JRC Global Human Settlement analysis platform for applications in support to global disaster risk reduction initiatives (DRR) and regional analysis in the frame of the European Cohesion policy. GHSL analysis platform uses geo-spatial data, primarily remotely sensed and population. GHSL also cooperates with the Group on Earth Observation on SB-04-Global Urban Observation and Information, and various international partners andWorld Bank and United Nations agencies. Some preliminary results integrating global human settlement information extracted from Landsat data records of the last 40 years and population data are presented.

  20. Evidence Report: Risk of Inadequate Human-Computer Interaction

    NASA Technical Reports Server (NTRS)

    Holden, Kritina; Ezer, Neta; Vos, Gordon

    2013-01-01

    Human-computer interaction (HCI) encompasses all the methods by which humans and computer-based systems communicate, share information, and accomplish tasks. When HCI is poorly designed, crews have difficulty entering, navigating, accessing, and understanding information. HCI has rarely been studied in an operational spaceflight context, and detailed performance data that would support evaluation of HCI have not been collected; thus, we draw much of our evidence from post-spaceflight crew comments, and from other safety-critical domains like ground-based power plants, and aviation. Additionally, there is a concern that any potential or real issues to date may have been masked by the fact that crews have near constant access to ground controllers, who monitor for errors, correct mistakes, and provide additional information needed to complete tasks. We do not know what types of HCI issues might arise without this "safety net". Exploration missions will test this concern, as crews may be operating autonomously due to communication delays and blackouts. Crew survival will be heavily dependent on available electronic information for just-in-time training, procedure execution, and vehicle or system maintenance; hence, the criticality of the Risk of Inadequate HCI. Future work must focus on identifying the most important contributing risk factors, evaluating their contribution to the overall risk, and developing appropriate mitigations. The Risk of Inadequate HCI includes eight core contributing factors based on the Human Factors Analysis and Classification System (HFACS): (1) Requirements, policies, and design processes, (2) Information resources and support, (3) Allocation of attention, (4) Cognitive overload, (5) Environmentally induced perceptual changes, (6) Misperception and misinterpretation of displayed information, (7) Spatial disorientation, and (8) Displays and controls.

  1. 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.

  2. Reproducibility and Transparency of Omics Research - Impacts on Human Health Risk Assessment

    EPA Science Inventory

    Omics technologies are becoming more widely used in toxicology, necessitating their consideration in human health hazard and risk assessment programs. Today, risk assessors in the United States Environmental Protection Agency’s Integrated Risk Information System (IRIS) Toxicologi...

  3. On the evolution of hoarding, risk-taking, and wealth distribution in nonhuman and human populations.

    PubMed

    Bergstrom, Theodore C

    2014-07-22

    This paper applies the theory of the evolution of risk-taking in the presence of idiosyncratic and environmental risks to the example of food hoarding by animals and explores implications of the resulting theory for human attitudes toward risk.

  4. Human Health Risk Assessment Calculator. In: SMARTe20ll, EPA/600/C-10/007

    EPA Science Inventory

    This calculator is aimed at supporting a human health risk assessment. Risk scenarios can be built by combining various health effects, exposure pathways, exposure parameters, and analytes. Scenario risk are calculated for each exposure pathway and analyte combination. The out...

  5. Probiotics in Human Immunodeficiency Virus Infection: A Systematic Review and Evidence Synthesis of Benefits and Risks

    PubMed Central

    Carter, George M.; Esmaeili, Aryan; Shah, Hardikkumar; Indyk, Debbie; Johnson, Matthew; Andreae, Michael; Sacks, Henry S.

    2016-01-01

    People living with human immunodeficiency virus frequently use dietary supplements, including probiotics, but concern exists about ingesting live organisms. We performed a systematic review of the benefits of probiotics and a meta-analysis of sepsis risk. We undertook a protocol-driven, comprehensive review to identify all relevant studies, assess their quality, and summarize the evidence. Of 2068 references, 27 were analyzed. The data suggest possible benefits for CD4 count, recurrence or management of bacterial vaginosis, and diarrhea management. We examined randomized, controlled studies explicitly assessing sepsis in any patient population, and we found zero cases of supplement-associated bacteremia or fungemia in 39 randomized controlled trials comprising 9402 subjects. The estimated number needed to harm is 7369 in Bayesian approach (95% credible interval: 1689, ∞), which should reassure clinicians. No or mild adverse effects were reported. Longer duration studies investigating different individual and mixed strains for plausible indications are needed to establish best practices. PMID:27747250

  6. 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.

  7. 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

  8. Behavioral Attention: A Longitudinal Study of Whether and How It Influences the Development of Word Reading and Reading Comprehension among At-Risk Readers

    ERIC Educational Resources Information Center

    Miller, Amanda C.; Fuchs, Douglas; Fuchs, Lynn S.; Compton, Donald; Kearns, Devin; Zhang, Wenjuan; Yen, Loulee; Patton, Samuel; Kirchner, Danielle Peterson

    2014-01-01

    The purpose of this study was to examine the extent to which teacher ratings of behavioral attention predicted responsiveness to word reading instruction in first-grade and third-grade reading comprehension performance. Participants were 110 first-grade students identified as at risk for reading difficulties who received 20 weeks of intensive…

  9. The Effect of Activity with E-Book on Vocabulary and Story Comprehension: A Comparison between Kindergarteners at Risk of Learning Disabilities and Typically Developing Kindergarteners

    ERIC Educational Resources Information Center

    Shamir, Adina; Korat, Ofra; Shlafer, Inessa

    2011-01-01

    The purpose of the current study was to investigate the effectiveness of e-book activity for vocabulary acquisition and story comprehension among kindergarteners at risk for learning disabilities (LD) as opposed to typically developing (TD) children. Participants included 136 children aged between five and seven (M = 71.2; SD = 5.64, in months),…

  10. Comprehensive Environmental Assessment Applied to Multiwalled Carbon Nanotube Flame-Retardant Coatings in Upholstery Textiles: A Case Study Presenting Priority Research Gaps for Future Risk Assessments (Final Report)

    EPA Science Inventory

    In September 2013, EPA announced the availability of the final report, Comprehensive Environmental Assessment Applied to Multiwalled Carbon Nanotube Flame-Retardant Coatings in Upholstery Textiles: A Case Study Presenting Priority Research Gaps for Future Risk Assessments...

  11. CSLAA and FAA'S Rules: Incorporating a 'Risk Management Framework' to Minimise Human Space Flight Risks

    NASA Astrophysics Data System (ADS)

    Chaddha, S.

    2012-01-01

    th This year marks the 50 anniversary of a landmark victory for humankind in its endeavour of entering and exploring the final frontier. During these years of space activity, we have witnessed a number of cumulative successes. One of which is the emergence of the commercial human space flight, or "space tourism", market. Commercial companies have the aim of travelling people into space safely and affordably. This paper shall consider the U.S. regulatory framework governing the space tourism market. It scrutinises the adequacy of the Commercial Space Launch and Amendment Act of 2004 (CSLAA), as bolstered by the FAA's requirements, to protect launching passengers to an acceptable standard of safety from the inherent risks associated with human space flights. It is argued that the legislative regime embeds a three-limb "risk management framework" as an appropriate response to address the concern over the safety of public space travel.

  12. Probabilistic integrated risk assessment of human exposure risk to environmental bisphenol A pollution sources.

    PubMed

    Fu, Keng-Yen; Cheng, Yi-Hsien; Chio, Chia-Pin; Liao, Chung-Min

    2016-10-01

    Environmental bisphenol A (BPA) exposure has been linked to a variety of adverse health effects such as developmental and reproductive issues. However, establishing a clear association between BPA and the likelihood of human health is complex yet fundamentally uncertain. The purpose of this study was to assess the potential exposure risks from environmental BPA among Chinese population based on five human health outcomes, namely immune response, uterotrophic assay, cardiovascular disease (CVD), diabetes, and behavior change. We addressed these health concerns by using a stochastic integrated risk assessment approach. The BPA dose-dependent likelihood of effects was reconstructed by a series of Hill models based on animal models or epidemiological data. We developed a physiologically based pharmacokinetic (PBPK) model that allows estimation of urinary BPA concentration from external exposures. Here we showed that the daily average exposure concentrations of BPA and urinary BPA estimates were consistent with the published data. We found that BPA exposures were less likely to pose significant risks for infants (0-1 year) and adults (male and female >20 years) with <10(-6)-fold increase in uterus weight and immune response outcomes, respectively. Moreover, our results indicated that there was 50 % risk probability that the response outcomes of CVD, diabetes, and behavior change with or without skin absorption would increase 10(-4)-10(-2)-fold. We conclude that our approach provides a powerful tool for tracking and managing human long-term BPA susceptibility in relation to multiple exposure pathways, and for informing the public of the negligible magnitude of environmental BPA pollution impacts on human health.

  13. Internal Fat and Cardiometabolic Risk Factors Following a Meal-Replacement Regimen vs. Comprehensive Lifestyle Changes in Obese Subjects

    PubMed Central

    König, Daniel; Zdzieblik, Denise; Deibert, Peter; Berg, Aloys; Gollhofer, Albert; Büchert, Martin

    2015-01-01

    The aim of the present study was to investigate the effect of a meal-replacement regimen vs. comprehensive lifestyle changes in overweight or obese subjects on intra-abdominal fat stores (Magnetic Resonance Imaging (MRI) measurements) and cardiometabolic risk factors. Forty-two obese men (n = 18) and women (n = 24) (age 49 ± 8 years; weight 96.3 ± 12.1 kg; BMI 32.7 ± 2.3 kg/m2) were selected for this randomized parallel-group design investigation. Subjects in the lifestyle group (LS-G; n = 22) received dietary counselling sessions and instructions how to increase physical activity. In the meal replacement group (MR-G; n = 20) meals were replaced by a low-calorie drink high in soy protein. After six months, subjects in the LS-G lost 8.88 ± 6.24 kg and subjects in the MR-G lost 7.1 ± 2.33 kg; p < 0.01 for changes within groups; no significant differences were found between the groups. Lean body mass remained constant in both intervention groups. MRI analyses showed that internal fat was significantly reduced in both groups to a comparable amount; the higher fat loss in the LS-G in the abdominal area was due to a higher reduction in subcutaneous fat. Both interventions significantly reduced components of the cardiometabolic risk profile and leptin levels. The decrease in the adipokines fetuin A and resistin was more pronounced in the MR-G. In conclusion, both interventions significantly reduced body weight, total fat mass and internal abdominal fat while preserving lean body mass. The reduction in the adipokines fetuin A and resistin was more pronounced in the meal replacement group suggesting an additional effect of soy protein components. PMID:26633473

  14. Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review.

    PubMed

    Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David

    2017-01-01

    Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a "stocking and glove" distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the

  15. Internal Fat and Cardiometabolic Risk Factors Following a Meal-Replacement Regimen vs. Comprehensive Lifestyle Changes in Obese Subjects.

    PubMed

    König, Daniel; Zdzieblik, Denise; Deibert, Peter; Berg, Aloys; Gollhofer, Albert; Büchert, Martin

    2015-12-01

    The aim of the present study was to investigate the effect of a meal-replacement regimen vs. comprehensive lifestyle changes in overweight or obese subjects on intra-abdominal fat stores (Magnetic Resonance Imaging (MRI) measurements) and cardiometabolic risk factors. Forty-two obese men (n = 18) and women (n = 24) (age 49 ± 8 years; weight 96.3 ± 12.1 kg; BMI 32.7 ± 2.3 kg/m2) were selected for this randomized parallel-group design investigation. Subjects in the lifestyle group (LS-G; n = 22) received dietary counselling sessions and instructions how to increase physical activity. In the meal replacement group (MR-G; n = 20) meals were replaced by a low-calorie drink high in soy protein. After six months, subjects in the LS-G lost 8.88 ± 6.24 kg and subjects in the MR-G lost 7.1 ± 2.33 kg; p < 0.01 for changes within groups; no significant differences were found between the groups. Lean body mass remained constant in both intervention groups. MRI analyses showed that internal fat was significantly reduced in both groups to a comparable amount; the higher fat loss in the LS-G in the abdominal area was due to a higher reduction in subcutaneous fat. Both interventions significantly reduced components of the cardiometabolic risk profile and leptin levels. The decrease in the adipokines fetuin A and resistin was more pronounced in the MR-G. In conclusion, both interventions significantly reduced body weight, total fat mass and internal abdominal fat while preserving lean body mass. The reduction in the adipokines fetuin A and resistin was more pronounced in the meal replacement group suggesting an additional effect of soy protein components.

  16. Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

    PubMed Central

    Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David

    2017-01-01

    Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in

  17. 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…

  18. Circadian misalignment increases cardiovascular disease risk factors in humans

    PubMed Central

    Morris, Christopher J.; Purvis, Taylor E.; Hu, Kun; Scheer, Frank A. J. L.

    2016-01-01

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID:26858430

  19. Circadian misalignment increases cardiovascular disease risk factors in humans.

    PubMed

    Morris, Christopher J; Purvis, Taylor E; Hu, Kun; Scheer, Frank A J L

    2016-03-08

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

  20. Dengue Seroprevalence and Risk Factors for Past and Recent Viral Transmission in Venezuela: A Comprehensive Community-Based Study

    PubMed Central

    Velasco-Salas, Zoraida I.; Sierra, Gloria M.; Guzmán, Diamelis M.; Zambrano, Julio; Vivas, Daniel; Comach, Guillermo; Wilschut, Jan C.; Tami, Adriana

    2014-01-01

    Dengue transmission in Venezuela has become perennial and a major public health problem. The increase in frequency and magnitude of recent epidemics prompted a comprehensive community-based cross-sectional study of 2,014 individuals in high-incidence neighborhoods of Maracay, Venezuela. We found a high seroprevalence (77.4%), with 10% of people experiencing recent infections. Multivariate logistic regression analysis showed that poverty-related socioeconomic factors (place and duration of residence, crowding, household size, and living in a shack) and factors/constraints related to intradomiciliary potential mosquito breeding sites (storing water and used tires) were linked with a greater risk of acquiring a dengue infection. Our results also suggest that transmission occurs mainly at home. The combination of increasingly crowded living conditions, growing population density, precarious homes, and water storage issues caused by enduring problems in public services in Maracay are the most likely factors that determine the permanent dengue transmission and the failure of vector control programs. PMID:25223944

  1. Dengue seroprevalence and risk factors for past and recent viral transmission in Venezuela: a comprehensive community-based study.

    PubMed

    Velasco-Salas, Zoraida I; Sierra, Gloria M; Guzmán, Diamelis M; Zambrano, Julio; Vivas, Daniel; Comach, Guillermo; Wilschut, Jan C; Tami, Adriana

    2014-11-01

    Dengue transmission in Venezuela has become perennial and a major public health problem. The increase in frequency and magnitude of recent epidemics prompted a comprehensive community-based cross-sectional study of 2,014 individuals in high-incidence neighborhoods of Maracay, Venezuela. We found a high seroprevalence (77.4%), with 10% of people experiencing recent infections. Multivariate logistic regression analysis showed that poverty-related socioeconomic factors (place and duration of residence, crowding, household size, and living in a shack) and factors/constraints related to intradomiciliary potential mosquito breeding sites (storing water and used tires) were linked with a greater risk of acquiring a dengue infection. Our results also suggest that transmission occurs mainly at home. The combination of increasingly crowded living conditions, growing population density, precarious homes, and water storage issues caused by enduring problems in public services in Maracay are the most likely factors that determine the permanent dengue transmission and the failure of vector control programs.

  2. Risk factors for human brucellosis in northern Jordan.

    PubMed

    Abo-Shehada, M N; Abu-Halaweh, M

    2013-02-01

    Little is known about the risk factors of human brucellosis in Jordan. A case-control study was conducted involving 56 Jordanians who had been treated for brucellosis and at least 3 matched controls for each case (n = 247). Matching was for sex, age, locality (the same village) and socioeconomic standard. Univariate and multivariate logistic regression analyses were used. In all, 17 risk factors were examined related to: contact with various livestock, milk and milk product consumption, drinking-water treatment and disease awareness. Most variables were associated with brucellosis in the univariate analysis but the final logistic model included only 4: milking sheep and goats (OR 3.5), consumption of raw feta cheese made from sheep and goat milk (OR 2.8) and consumption of cows' milk (OR 0.4) and boiled feta cheese (OR 0.4). Small ruminant farmers need to be trained in safer milking practices and feta cheese making procedures.

  3. Hair dye use and risk of human cancer.

    PubMed

    Zhang, Yawei; Kim, Christopher; Zheng, Tongzhang

    2012-01-01

    Over 50% of the adult population will use hair dyes at some point in their lifetimes. Hair dyes consist of various chemicals and the composition of these chemicals vary by hair dye types. Chemicals p-phenylenediamine and aminophenyl have been suggested as possible carcinogens or mutagens in experimental studies. The scientific community has been interested in this potential public health impact and the results of published epidemiological studies are summarized here. The current evidence provides limited evidences on the association between personal hair dye use and human cancer risk, except for the possibility of hematopoietic cancers and to a lesser extent, bladder cancer. Risk appears to be affected by time period of use and by specific genetic polymorphisms. Future studies should investigate potential gene and environment interaction to assess possible genetic susceptibility. Several methodological issues should also be considered in future studies including completed hair dye use information such as on timing, duration, frequency and type of hair dye product use.

  4. Reducing the Risk of Human Missions to Mars Through Testing

    NASA Astrophysics Data System (ADS)

    Drake, Bret G.

    2007-07-01

    During the summer of 2002 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. The previous NASA Exploration Team (NEXT) activities laid the foundation and framework for development of NASA s Integrated Space Plan. The reference missions resulting from the analysis performed by the Exploration Blueprint team formed the basis for requirement definition, systems development, technology roadmapping, and risk assessments for future human exploration beyond low-Earth orbit. Emphasis was placed on developing recommendations on what could be done now to effect future exploration activities. The Exploration Blueprint team embraced the Stepping Stone approach to exploration where human and robotic activities are conducted through progressive expansion outward beyond low- Earth orbit. Results from this study produced a long-term strategy for exploration with near-term implementation plans, program recommendations, and technology investments. Specific results included the development of a common exploration crew vehicle concept, a unified space nuclear strategy, focused bioastronautics research objectives, and an integrated human and robotic exploration strategy. Recommendations from the Exploration Blueprint included the endorsement of the Nuclear Systems Initiative, augmentation of the bioastronautics research, a focused space transportation program including heavy-lift launch and a common exploration vehicle design for ISS and exploration missions, as well as an integrated human and robotic exploration strategy for Mars. Following the results of the Exploration Blueprint study, the NASA Administrator has asked for a recommendation by June, 2003 on the next steps in human and robotic exploration in

  5. Reducing the Risk of Human Missions to Mars Through Testing

    NASA Technical Reports Server (NTRS)

    Drake, Bret G.

    2007-01-01

    During the summer of 2002 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. The previous NASA Exploration Team (NEXT) activities laid the foundation and framework for development of NASA s Integrated Space Plan. The reference missions resulting from the analysis performed by the Exploration Blueprint team formed the basis for requirement definition, systems development, technology roadmapping, and risk assessments for future human exploration beyond low-Earth orbit. Emphasis was placed on developing recommendations on what could be done now to effect future exploration activities. The Exploration Blueprint team embraced the Stepping Stone approach to exploration where human and robotic activities are conducted through progressive expansion outward beyond low- Earth orbit. Results from this study produced a long-term strategy for exploration with near-term implementation plans, program recommendations, and technology investments. Specific results included the development of a common exploration crew vehicle concept, a unified space nuclear strategy, focused bioastronautics research objectives, and an integrated human and robotic exploration strategy. Recommendations from the Exploration Blueprint included the endorsement of the Nuclear Systems Initiative, augmentation of the bioastronautics research, a focused space transportation program including heavy-lift launch and a common exploration vehicle design for ISS and exploration missions, as well as an integrated human and robotic exploration strategy for Mars. Following the results of the Exploration Blueprint study, the NASA Administrator has asked for a recommendation by June, 2003 on the next steps in human and robotic exploration in

  6. 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

  7. 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.

  8. Characterization of Evidence for Human System Risk Assessment

    NASA Technical Reports Server (NTRS)

    Steinberg, S. L.; Van Baalen, M.; Rossi, M.; Riccio, G.; Romero, E.; Francisco, D.

    2016-01-01

    Understanding the kinds of evidence available and using the best evidence to answer a question is critical to evidenced-based decision-making, and it requires synthesis of evidence from a variety of sources. Categorization of human system risks in spaceflight, in particular, focuses on how well the integration and interpretation of all available evidence informs the risk statement that describes the relationship between spaceflight hazards and an outcome of interest. A mature understanding and categorization of these risks requires: 1) sufficient characterization of risk, 2) sufficient knowledge to determine an acceptable level of risk (i.e., a standard), 3) development of mitigations to meet the acceptable level of risk, and 4) identification of factors affecting generalizability of the evidence to different design reference missions. In the medical research community, evidence is often ranked by increasing confidence in findings gleaned from observational and experimental research (e.g., "levels of evidence"). However, an approach based solely on aspects of experimental design is problematic in assessing human system risks for spaceflight. For spaceflight, the unique challenges and opportunities include: (1) The independent variables in most evidence are the hazards of spaceflight, such as space radiation or low gravity, which cannot be entirely duplicated in terrestrial (Earth-based) analogs, (2) Evidence is drawn from multiple sources including medical and mission operations, Lifetime Surveillance of Astronaut Health (LSAH), spaceflight research (LSDA), and relevant environmental & terrestrial databases, (3) Risk metrics based primarily on LSAH data are typically derived from available prevalence or incidence data, which may limit rigorous interpretation, (4) The timeframe for obtaining adequate spaceflight sample size (n) is very long, given the small population, (5) Randomized controlled trials are unattainable in spaceflight, (6) Collection of personal and

  9. Behavioral Attention: A Longitudinal Study of Whether and How It Influences the Development of Word Reading and Reading Comprehension among At-Risk Readers.

    PubMed

    Miller, Amanda C; Fuchs, Douglas; Fuchs, Lynn S; Compton, Donald L; Kearns, Devin; Zhang, Wenjuan; Yen, Loulee; Patton, Samuel; Kirchner, Danielle

    2014-07-01

    The purpose of this study was to examine the extent to which teacher ratings of behavioral attention predicted responsiveness to word reading instruction in first grade and third-grade reading comprehension performance. Participants were 110 first grade students identified as at-risk for reading difficulties who received 20 weeks of intensive reading intervention in combination with classroom reading instruction. Path analysis indicated that teacher ratings of student attention significantly predicted students' word reading growth in first grade even when they were competed against other relevant predictors (phonological awareness, nonword reading, sight word efficiency, vocabulary, listening comprehension, hyperactivity, nonverbal reasoning, and short term memory). Also, student attention demonstrated a significant indirect effect on third grade reading comprehension via word reading, but not via listening comprehension. Results suggest that student attention (indexed by teacher ratings) is an important predictor of at-risk readers' responsiveness to reading instruction in first grade and that first-grade reading growth mediates the relationship between students' attention and their future level of reading comprehension. The importance of considering ways to manage and improve behavioral attention when implementing reading instruction is discussed.

  10. Behavioral Attention: A Longitudinal Study of Whether and How It Influences the Development of Word Reading and Reading Comprehension among At-Risk Readers

    PubMed Central

    Miller, Amanda C.; Fuchs, Douglas; Fuchs, Lynn S.; Compton, Donald L.; Kearns, Devin; Zhang, Wenjuan; Yen, Loulee; Patton, Samuel; Kirchner, Danielle

    2014-01-01

    The purpose of this study was to examine the extent to which teacher ratings of behavioral attention predicted responsiveness to word reading instruction in first grade and third-grade reading comprehension performance. Participants were 110 first grade students identified as at-risk for reading difficulties who received 20 weeks of intensive reading intervention in combination with classroom reading instruction. Path analysis indicated that teacher ratings of student attention significantly predicted students’ word reading growth in first grade even when they were competed against other relevant predictors (phonological awareness, nonword reading, sight word efficiency, vocabulary, listening comprehension, hyperactivity, nonverbal reasoning, and short term memory). Also, student attention demonstrated a significant indirect effect on third grade reading comprehension via word reading, but not via listening comprehension. Results suggest that student attention (indexed by teacher ratings) is an important predictor of at-risk readers’ responsiveness to reading instruction in first grade and that first-grade reading growth mediates the relationship between students’ attention and their future level of reading comprehension. The importance of considering ways to manage and improve behavioral attention when implementing reading instruction is discussed. PMID:25110548

  11. Human Trafficking in Nepal: Post-Earthquake Risk and Response.

    PubMed

    Gyawali, Bishal; Keeling, June; Kallestrup, Per

    2016-09-15

    As Nepal mourns the 1-year commemoration of the April 2015 earthquake and its aftershocks that killed more than 8500 people and left thousands injured and displaced, other more hidden repercussions of the resultant chaotic environment need attention: the increased risk of human trafficking. Considering that natural disasters provide a milieu for this illicit trade, there is a need for a robust response from stakeholders such as donors, civil society organizations, and government organizations against human trafficking following disasters such as the Nepal earthquake. Responsibility to prevent and fight trafficking should be explicitly included in the mandate of relief and rehabilitation mechanisms set up at the national level to coordinate the disaster relief response, serving to support populations in both rural and urban areas. (Disaster Med Public Health Preparedness. 2016;page 1 of 2).

  12. The risks and benefits of human donor breast milk.

    PubMed

    Brent, Nancy

    2013-05-01

    CME EDUCATIONAL OBJECTIVES: 1.Review the advantages and disadvantages of donor-banked milk over informal milk sharing.2.List disadvantages of proprietary infant formula for use as supplementation.3.Determine the primary ethical concerns when electing to use donor human milk versus propriety infant formula for supplementation. The benefits of breast-feeding, as well as the risks of some artificial formula, are well known. This growing recognition of the advantages of breast-feeding is reflected in the increased incidence of breast-feeding in recent years. However, one of the most common reasons for premature weaning is low milk supply, perceived or real, followed by nipple or breast pain. Given the increased awareness of the superiority of breast milk, however, more parents are turning to human donor milk to supplement their babies after they have been weaned.

  13. Advancing human health risk assessment: Integrating recent advisory committee recommendations

    PubMed Central

    Becker, Richard A.; Haber, Lynne T.; Pottenger, Lynn H.; Bredfeldt, Tiffany; Fenner-Crisp, Penelope A.

    2013-01-01

    Over the last dozen years, many national and international expert groups have considered specific improvements to risk assessment. Many of their stated recommendations are mutually supportive, but others appear conflicting, at least in an initial assessment. This review identifies areas of consensus and difference and recommends a practical, biology-centric course forward, which includes: (1) incorporating a clear problem formulation at the outset of the assessment with a level of complexity that is appropriate for informing the relevant risk management decision; (2) using toxicokinetics and toxicodynamic information to develop Chemical Specific Adjustment Factors (CSAF); (3) using mode of action (MOA) information and an understanding of the relevant biology as the key, central organizing principle for the risk assessment; (4) integrating MOA information into dose–response assessments using existing guidelines for non-cancer and cancer assessments; (5) using a tiered, iterative approach developed by the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) as a scientifically robust, fit-for-purpose approach for risk assessment of combined exposures (chemical mixtures); and (6) applying all of this knowledge to enable interpretation of human biomonitoring data in a risk context. While scientifically based defaults will remain important and useful when data on CSAF or MOA to refine an assessment are absent or insufficient, assessments should always strive to use these data. The use of available 21st century knowledge of biological processes, clinical findings, chemical interactions, and dose–response at the molecular, cellular, organ and organism levels will minimize the need for extrapolation and reliance on default approaches. PMID:23844697

  14. Human Research Program Human Health Countermeasures Element Sensorimotor Risk Standing Review Panel (SRP) Final Report

    NASA Technical Reports Server (NTRS)

    Peterson, Barry

    2009-01-01

    The Sensorimotor Risk Standing Review Panel (SRP) met at the NASA Johnson Space Center on October 4-6, 2009 to discuss the areas of future research targeted by the Human Health Countermeasures (HHC) Element of the Human Research Program (HRP). Using evidence-based knowledge as a background for risks, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Sensorimotor 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 SRP's review. 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 risks 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 address the specific risks. 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. The SRP made a final debriefing to the HRP Program Scientist. Taking the evidence and the risk as givens, the SRP reached the following conclusions: 1) the panel is very supportive of and endorses the present activities of the Sensorimotor Risk; and the panel is likewise supportive of the gaps and associated tasks in the IRP; 2) overall, the tasks addressed the gaps in the IRP; 3) there were some gaps and tasks that merit further enhancement and some new gaps/tasks that the SRP recommends.

  15. Bayesian Safety Risk Modeling of Human-Flightdeck Automation Interaction

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Shih, Ann T.

    2015-01-01

    Usage of automatic systems in airliners has increased fuel efficiency, added extra capabilities, enhanced safety and reliability, as well as provide improved passenger comfort since its introduction in the late 80's. However, original automation benefits, including reduced flight crew workload, human errors or training requirements, were not achieved as originally expected. Instead, automation introduced new failure modes, redistributed, and sometimes increased workload, brought in new cognitive and attention demands, and increased training requirements. Modern airliners have numerous flight modes, providing more flexibility (and inherently more complexity) to the flight crew. However, the price to pay for the increased flexibility is the need for increased mode awareness, as well as the need to supervise, understand, and predict automated system behavior. Also, over-reliance on automation is linked to manual flight skill degradation and complacency in commercial pilots. As a result, recent accidents involving human errors are often caused by the interactions between humans and the automated systems (e.g., the breakdown in man-machine coordination), deteriorated manual flying skills, and/or loss of situational awareness due to heavy dependence on automated systems. This paper describes the development of the increased complexity and reliance on automation baseline model, named FLAP for FLightdeck Automation Problems. The model development process starts with a comprehensive literature review followed by the construction of a framework comprised of high-level causal factors leading to an automation-related flight anomaly. The framework was then converted into a Bayesian Belief Network (BBN) using the Hugin Software v7.8. The effects of automation on flight crew are incorporated into the model, including flight skill degradation, increased cognitive demand and training requirements along with their interactions. Besides flight crew deficiencies, automation system

  16. A Study of Seventh-Graders Comprehensions of Human Reproduction Concepts

    ERIC Educational Resources Information Center

    Barrow, Lloyd Harley

    1977-01-01

    Study of an Iowa junior high school revealed that: (1) seventh grade pupils' knowledge levels were raised after studying human reproduction concepts and that (2) the pupils were of the opinion that human reproduction studies should be included in life science classes. (MB)

  17. Understanding the Human Genome Project: Using Stations to Provide a Comprehensive Overview

    ERIC Educational Resources Information Center

    Soto, Julio G.

    2005-01-01

    A lesson was designed for lower division general education, non-major biology lecture-only course that included the historical and scientific context, some of the skills used to study the human genome, results, conclusions and ethical consideration. Students learn to examine and compare the published Human Genome maps, and employ the strategies…

  18. Human health risk assessment from arsenic exposures in Bangladesh.

    PubMed

    Joseph, Tijo; Dubey, Brajesh; McBean, Edward A

    2015-09-15

    High arsenic exposures, prevalent through dietary and non-dietary sources in Bangladesh, present a major health risk to the public. A quantitative human health risk assessment is described as a result of arsenic exposure through food and water intake, tea intake, accidental soil ingestion, and chewing of betel quid, while people meet their desirable dietary intake requirements throughout their lifetime. In evaluating the contribution of each intake pathway to average daily arsenic intake, the results show that food and water intake combined, makes up approximately 98% of the daily arsenic intake with the balance contributed to by intake pathways such as tea consumption, soil ingestion, and quid consumption. Under an exposure scenario where arsenic concentration in water is at the WHO guideline (0.01 mg/L), food intake is the major arsenic intake pathway ranging from 67% to 80% of the average daily arsenic intake. However, the contribution from food drops to a range of 29% to 45% for an exposure scenario where arsenic in water is at the Bangladesh standard (0.05 mg/L). The lifetime excess risk of cancer occurrence from chronic arsenic exposure, considering a population of 160 million people, based on an exposure scenario with 85 million people at the WHO guideline value and 75 million people at the Bangladesh standard, and assuming that 35 million people are associated with a heavy activity level, is estimated as 1.15 million cases.

  19. Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model.

    PubMed

    Guo, Yong; He, Bin; Xu, Xiangbo; Wang, Jiedong

    2011-02-17

    In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

  20. Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

    PubMed Central

    Hao, Jian-Jiang; Zhi, Xiaofei; Wang, Yeming; Zhang, Zheng; Hao, Zeyu; Ye, Rong; Tang, Zhijie; Qian, Fei; Wang, Quhui; Zhu, Jianwei

    2017-01-01

    The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype. PMID:28181595

  1. Context-dependent semantic processing in the human brain: evidence from idiom comprehension.

    PubMed

    Rommers, Joost; Dijkstra, Ton; Bastiaansen, Marcel

    2013-05-01

    Language comprehension involves activating word meanings and integrating them with the sentence context. This study examined whether these routines are carried out even when they are theoretically unnecessary, namely, in the case of opaque idiomatic expressions, for which the literal word meanings are unrelated to the overall meaning of the expression. Predictable words in sentences were replaced by a semantically related or unrelated word. In literal sentences, this yielded previously established behavioral and electrophysiological signatures of semantic processing: semantic facilitation in lexical decision, a reduced N400 for semantically related relative to unrelated words, and a power increase in the gamma frequency band that was disrupted by semantic violations. However, the same manipulations in idioms yielded none of these effects. Instead, semantic violations elicited a late positivity in idioms. Moreover, gamma band power was lower in correct idioms than in correct literal sentences. It is argued that the brain's semantic expectancy and literal word meaning integration operations can, to some extent, be "switched off" when the context renders them unnecessary. Furthermore, the results lend support to models of idiom comprehension that involve unitary idiom representations.

  2. Tenth Warren K. Sinclair keynote address-the Fukushima nuclear power plant accident and comprehensive health risk management.

    PubMed

    Yamashita, Shunichi

    2014-02-01

    Just two years have passed since the Tokyo Electric Power Company-Fukushima Daiichi Nuclear Power Plant (NPP) accident, a multidimensional disaster that combined to destroy the local infrastructure on which the safety system depended and gave a serious impact to the world. Countermeasures including evacuation, sheltering, and control of the food chain were implemented in a timely manner by the Japanese government. However, there is a clear need for improvement, especially in the areas of nuclear safety and protection and also in the management of the radiation health risk during and even after the accident. To date there have been no acute radiation injuries. The radiation-related physical health consequences to the general public, including evacuees, are likely to be much lower than those arising from the Chernobyl nuclear reactor accident, because the radiation fallout and the subsequent environmental contamination were much more limited. However, the social, psychological, and economic impacts of the Fukushima NPP accident are expected to be considerable. Currently, continued monitoring and characterization of the levels of radioactivity in the environment and foods in Fukushima are vital for obtaining informed consent to the decisions on living in the areas already radiocontaminated and returning back to the evacuated areas once re-entry is permitted; it is also important to perform a realistic assessment of the radiation doses on the basis of measurements. We are currently implementing the official plans of the Fukushima Health Management Survey, which includes a basic survey for the estimation of the external doses that were received during the first 4 mo after the accident and four more detailed surveys (thyroid ultrasound examination, comprehensive health check-up, mental health and life-style survey, and survey of pregnant women and nursing mothers), with the aim to take care of the health of all of the residents of the Fukushima Prefecture for a long time

  3. Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature.

    PubMed

    Ruiz-Colón, Kazandra; Chavez-Arias, Carlos; Díaz-Alcalá, José Eric; Martínez, María A

    2014-07-01

    Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies.

  4. Comprehensive mapping of protein N-glycosylation in human liver by combining hydrophilic interaction chromatography and hydrazide chemistry.

    PubMed

    Zhu, Jun; Sun, Zhen; Cheng, Kai; Chen, Rui; Ye, Mingliang; Xu, Bo; Sun, Deguang; Wang, Liming; Liu, Jing; Wang, Fangjun; Zou, Hanfa

    2014-03-07

    Although glycoproteomics is greatly developed in recent years, our knowledge about N-glycoproteome of human tissues is still very limited. In this study, we comprehensively mapped the N-glycosylation sites of human liver by combining click maltose-hydrophilic interaction chromatography (HILIC) and the improved hydrazide chemistry. The specificity could be as high as 90% for hydrazide chemistry and 80% for HILIC. Altogether, we identified 14,480 N-glycopeptides matched with N-!P-[S|T|C] sequence motif from human liver, corresponding to 2210 N-glycoproteins and 4783 N-glycosylation sites. These N-glycoproteins are widely involved into different types of biological processes, such as hepatic stellate cell activation and acute phase response of human liver, which all highly associate with the progression of liver diseases. Moreover, the exact N-glycosylation sites of some key-regulating proteins within different human liver physiological processes were also obtained, such as E-cadherin, transforming growth factor beta receptor and 29 members of G protein coupled receptors family.

  5. A comprehensive assessment of arsenic in commonly consumed foodstuffs to evaluate the potential health risk in Bangladesh.

    PubMed

    Ahmed, Md Kawser; Shaheen, Nazma; Islam, Md Saiful; Habibullah-Al-Mamun, Md; Islam, Saiful; Islam, Md Monirul; Kundu, Goutam Kumar; Bhattacharjee, Lalita

    2016-02-15

    Arsenic (As), particularly of its inorganic form (iAs) is highly toxic, and its presence in food composites is a matter of concern for the public health safety, specifically in Bangladesh which is regarded as the most arsenic affected country throughout the world. This study was carried out to investigate the levels of As in the composite samples of commonly consumed foodstuffs collected from 30 different agro-ecological zones for the first time in Bangladesh. Most of the individual food composites contain a considerable amount of As which was, as a whole, in the range of 0.077-1.5mg/kg fw which was lower than those reported from Spain, EU, France, Korea, whereas higher than those of Mexico, Chile, Japan, Cambodia, Hong Kong, Serbia, respectively. Cereals, vegetables, milk, and fish contribute about 90% to the daily intake of inorganic arsenic. Human health risk of dietary iAs was assessed separately for both the rural and urban adults. The estimated daily dietary intakes (EDI) of iAs for the exposed rural (3.5) and urban residents (3.2 μg/kg-BW/day) clearly exceeded the previous provisional tolerable daily intake (PTDI) value of 2.1 μg/kg-BW/day, recommended by the World Health Organization (WHO). From the health point of view, this study concluded that both the rural and urban residents of Bangladesh are exposed to carcinogenic and non-carcinogenic risks who consume As-contaminated water and foodstuffs.

  6. DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions

    PubMed Central

    Arjunan, Selvam; Sastri, Narayan P.; Chandra, Nagasuma

    2016-01-01

    Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue–human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue–human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/). PMID:27618709

  7. Addressing Human Variability in Next-Generation Human Health Risk Assessments of Environmental Chemicals

    PubMed Central

    Bois, Frederic Y.; Chiu, Weihsueh A.; Hattis, Dale; Rusyn, Ivan; Guyton, Kathryn Z.

    2012-01-01

    Background: Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Objective: Our goal was to explore how next-generation human health risk assessments may better characterize variability in the context of the conceptual framework for the source-to-outcome continuum. Methods: This review was informed by a National Research Council workshop titled “Biological Factors that Underlie Individual Susceptibility to Environmental Stressors and Their Implications for Decision-Making.” We considered current experimental and in silico approaches, and emerging data streams (such as genetically defined human cells lines, genetically diverse rodent models, human omic profiling, and genome-wide association studies) that are providing new types of information and models relevant for assessing interindividual variability for application to human health risk assessments of environmental chemicals. Discussion: One challenge for characterizing variability is the wide range of sources of inherent biological variability (e.g., genetic and epigenetic variants) among individuals. A second challenge is that each particular pair of health outcomes and chemical exposures involves combinations of these sources, which may be further compounded by extrinsic factors (e.g., diet, psychosocial stressors, other exogenous chemical exposures). A third challenge is that different decision contexts present distinct needs regarding the identification—and extent of characterization—of interindividual variability in the human population. Conclusions: Despite these inherent challenges, opportunities exist to incorporate evidence from emerging data streams for addressing interindividual variability in a range of decision-making contexts. PMID:23086705

  8. Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging

    PubMed Central

    Whiting, Chan C.; Siebert, Janet; Newman, Aaron M.; Du, Hong-wu; Alizadeh, Ash A.; Goronzy, Jorg; Weyand, Cornelia M.; Krishnan, Eswar; Fathman, C. Garrison; Maecker, Holden T.

    2015-01-01

    While many age-associated immune changes have been reported, a comprehensive set of metrics of immune aging is lacking. Here we report data from 243 healthy adults aged 40–97, for whom we measured clinical and functional parameters, serum cytokines, cytokines and gene expression in stimulated and unstimulated PBMC, PBMC phenotypes, and cytokine-stimulated pSTAT signaling in whole blood. Although highly heterogeneous across individuals, many of these assays revealed trends by age, sex, and CMV status, to greater or lesser degrees. Age, then sex and CMV status, showed the greatest impact on the immune system, as measured by the percentage of assay readouts with significant differences. An elastic net regression model could optimally predict age with 14 analytes from different assays. This reinforces the importance of multivariate analysis for defining a healthy immune system. These data provide a reference for others measuring immune parameters in older people. PMID:26197454

  9. Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

    PubMed

    Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

    2016-10-01

    The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

  10. Appraisal of potential environmental risks associated with human antibiotic consumption in Turkey.

    PubMed

    Turkdogan, F Ilter; Yetilmezsoy, Kaan

    2009-07-15

    A comprehensive analysis of Turkish antibiotic data was conducted to evaluate potential environmental risks associated with antibiotic consumption in Turkey for year 2007. Antibiotics were defined for systemic use or group J01 of the WHO Anatomical Therapeutic Chemical (ATC) classification system. Total emissions and prescriptions for each ATC group were classified separately into 17 different J01 categories and three forms of medication (capsule/tablets, injectables and suspensions). Capsules and tablets were found as the most emitted form of medication in year 2007, with a total emission rate of about 585.5 tons/year (76%). Total antibiotic emission rates including all forms of medications were determined to be about 664.2 tons/year (86%) and 110.1 tons/year (14%) for adult and pediatric patients, respectively. An environmental risk assessment of 8 human antibiotics was conducted according to the EU draft guidance (CEC/III/5504/94, draft 6, version 4) and the risk was indicated by the ratio of predicted environmental concentration (PEC) to predicted no effect concentration (PNEC) for the aquatic environment. Available acute and chronic toxicity data were collected from the open peer-reviewed literature to derive PNEC. Risk quotients (PEC/PNEC) were then calculated for 8 pharmaceutical substances. PEC/PNEC ratio exceeded 1.0 for beta-lactams (cephalosporins and penicillins), fluoroquinolones, macrolides and aminoglycosides. The findings of this study concluded that the release of these compounds from wastewater treatment plants may potentially be of an important environmental concern based on today's use of antibiotics in Turkey.

  11. Comprehensive genome-wide proteomic analysis of human placental tissue for the Chromosome-Centric Human Proteome Project.

    PubMed

    Lee, Hyoung-Joo; Jeong, Seul-Ki; Na, Keun; Lee, Min Jung; Lee, Sun Hee; Lim, Jong-Sun; Cha, Hyun-Jeong; Cho, Jin-Young; Kwon, Ja-Young; Kim, Hoguen; Song, Si Young; Yoo, Jong Shin; Park, Young Mok; Kim, Hail; Hancock, William S; Paik, Young-Ki

    2013-06-07

    As a starting point of the Chromosome-Centric Human Proteome Project (C-HPP), we established strategies of genome-wide proteomic analysis, including protein identification, quantitation of disease-specific proteins, and assessment of post-translational modifications, using paired human placental tissues from healthy and preeclampsia patients. This analysis resulted in identification of 4239 unique proteins with high confidence (two or more unique peptides with a false discovery rate less than 1%), covering 21% of approximately 20, 059 (Ensembl v69, Oct 2012) human proteins, among which 28 proteins exhibited differentially expressed preeclampsia-specific proteins. When these proteins are assigned to all human chromosomes, the pattern of the newly identified placental protein population is proportional to that of the gene count distribution of each chromosome. We also identified 219 unique N-linked glycopeptides, 592 unique phosphopeptides, and 66 chromosome 13-specific proteins. In particular, protein evidence of 14 genes previously known to be specifically up-regulated in human placenta was verified by mass spectrometry. With respect to the functional implication of these proteins, 38 proteins were found to be involved in regulatory factor biosynthesis or the immune system in the placenta, but the molecular mechanism of these proteins during pregnancy warrants further investigation. As far as we know, this work produced the highest number of proteins identified in the placenta and will be useful for annotating and mapping all proteins encoded in the human genome.

  12. Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians.

    PubMed

    Shen, Hui; Li, Jian; Zhang, Jigang; Xu, Chao; Jiang, Yan; Wu, Zikai; Zhao, Fuping; Liao, Li; Chen, Jun; Lin, Yong; Tian, Qing; Papasian, Christopher J; Deng, Hong-Wen

    2013-01-01

    Whole genome sequencing studies are essential to obtain a comprehensive understanding of the vast pattern of human genomic variations. Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×). We identified approximately 11 million single nucleotide polymorphisms (SNPs), 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96%) have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases.

  13. Significance of rat mammary tumors for human risk assessment.

    PubMed

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis.

  14. Wind turbines: is there a human health risk?

    PubMed

    Roberts, Jennifer D; Roberts, Mark A

    2013-04-01

    The term "Wind Turbine Syndrome" was coined in a recently self-published book, which hypothesized that a multitude of symptoms such as headache and dizziness resulted from wind turbines generating low frequency sound (LFS). The objective of this article is to provide a summary of the peer-reviewed literature on the research that has examined the relationship between human health effects and exposure to LFS and sound generated from the operation of wind turbines. At present, a specific health condition has not been documented in the peer-reviewed literature that has been classified as a disease caused by exposure to sound levels and frequencies generated by the operation of wind turbines. Communities are experiencing a heightened sense of annoyance and fear from the development and siting of wind turbine farms. High-quality research and effective risk communication can advance this course from one of panic to one of understanding and exemplification for other environmental advancements.

  15. QUANTITATIVE TOXICOPROTEOMIC ANALYSIS OF CARCINOGEN-TREATED ANIMAL TISSUES AND HUMAN CELLS FOR 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...

  16. Coconut oil consumption and cardiovascular risk factors in humans

    PubMed Central

    Eyres, Michael F.; Chisholm, Alexandra; Brown, Rachel C.

    2016-01-01

    Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease. PMID:26946252

  17. Coconut oil consumption and cardiovascular risk factors in humans.

    PubMed

    Eyres, Laurence; Eyres, Michael F; Chisholm, Alexandra; Brown, Rachel C

    2016-04-01

    Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.

  18. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    PubMed Central

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  19. Modeling human risk: Cell & molecular biology in context

    SciTech Connect

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  20. A comprehensive approach to determine the probiotic potential of human-derived Lactobacillus for industrial use.

    PubMed

    Gregoret, V; Perezlindo, M J; Vinderola, G; Reinheimer, J; Binetti, A

    2013-05-01

    Specific strains should only be regarded as probiotics if they fulfill certain safety, technological and functional criteria. The aim of this work was to study, from a comprehensive point of view (in vitro and in vivo tests), three Lactobacillus strains (Lactobacillus paracasei JP1, Lactobacillus rhamnosus 64 and Lactobacillus gasseri 37) isolated from feces of local newborns, determining some parameters of technological, biological and functional relevance. All strains were able to adequately grow in different economic culture media (cheese whey, buttermilk and milk), which were also suitable as cryoprotectants. As selective media, LP-MRS was more effective than B-MRS for the enumeration of all strains. The strains were resistant to different technological (frozen storage, high salt content) and biological (simulated gastrointestinal digestion after refrigerated storage in acidified milk, bile exposure) challenges. L. rhamnosus 64 and L. gasseri 37, in particular, were sensible to chloramphenicol, erythromycin, streptomycin, tetracycline and vancomycin, increased the phagocytic activity of peritoneal macrophage and induced the proliferation of IgA producing cells in small intestine when administered to mice. Even when clinical trails are still needed, both strains fulfilled the main criteria proposed by FAO/WHO to consider them as potential probiotics for the formulation of new foods.

  1. Human pharmaceuticals in US surface waters: a human health risk assessment.

    PubMed

    Schwab, Bradley W; Hayes, Eileen P; Fiori, Janice M; Mastrocco, Frank J; Roden, Nicholas M; Cragin, David; Meyerhoff, Roger D; D'Aco, Vincent J; Anderson, Paul D

    2005-08-01

    The detection of low levels of pharmaceuticals in rivers and streams, drinking water, and groundwater has raised questions as to whether these levels may affect human health. This report presents human health risk assessments for 26 active pharmaceutical ingredients (APIs) and/or their metabolites, representing 14 different drug classes, for which environmental monitoring data are available for the United States. Acceptable daily intakes (ADIs) are derived using the considerable data that are available for APIs. The resulting ADIs are designed to protect potentially exposed populations, including sensitive sub-populations. The ADIs are then used to estimate predicted no effect concentrations (PNECs) for two sources of potential human exposure: drinking water and fish ingestion. The PNECs are compared to measured environmental concentrations (MECs) from the published literature and to maximum predicted environmental concentrations (PECs) generated using the PhATE model. The PhATE model predictions are made under conservative assumptions of low river flow and no depletion (i.e., no metabolism, no removal during wastewater or drinking water treatment, and no instream depletion). Ratios of MECs to PNECs are typically very low and consistent with PEC to PNEC ratios. For all 26 compounds, these low ratios indicate that no appreciable human health risk exists from the presence of trace concentrations of these APIs in surface water and drinking water.

  2. Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment.

    PubMed

    Cunningham, Virginia L; Binks, Stephen P; Olson, Michael J

    2009-02-01

    Assessments for potential impact to human health from environmental exposures were carried out for 44 active pharmaceutical ingredients (APIs) marketed by GlaxoSmithKline (GSK), representing approximately 22 general pharmacological classes exhibiting a broad spectrum of therapeutic activities. These assessments use the considerable amount of information available on the human pharmacology and toxicology of the APIs to develop acceptable daily intakes (ADIs) which are believed to be without pharmacological or toxicological effect. With the exception of the anti-cancer drugs and some antibiotics, the minimum dose producing the intended therapeutic effect was typically used as the point of departure for calculation of ADIs. The ADI values were used to generate predicted no effect concentrations from environmental exposure for human health (PNEC(HH)s) from drinking water or fish consumption. These PNECs were compared to predicted environmental concentrations (PECs) calculated using the regional assessment models PhATE for North America and GREAT-ER for Europe. Risk was characterized by calculating the ratio of the 90th percentile PECs to the PNEC(HH)s. For the APIs reported here, these ratios are less than one for all of the compounds, varying from 7x10(-2) to 6x10(-11), indicating that based upon currently available data, these compounds do not appear to pose an appreciable risk to human health from potential environmental exposure from drinking water and fish consumption.

  3. NEW APPROACHES IN RISK ANALYSIS OF ENVIRONMENTAL STRESSORS TO HUMAN AND ECOLOGICAL SYSTEMS

    EPA Science Inventory

    We explore the application of novel techniques for improving and integrating risk analysis of environmental stressors to human and ecological systems. Environmental protection decisions are guided by risk assessments serving as tools to develop regulatory policy and other relate...

  4. Evaluating uncertainty to strengthen epidemiologic data for use in human health risk assessments

    EPA Science Inventory

    Background: There is a recognized need to improve the application of epidemiologic data in human health risk assessment especially for understanding and characterizing risks from environmental and occupational exposures. While most epidemiologic studies result in uncertainty, tec...

  5. Titanium Dioxide Nanoparticles: a Risk for Human Health?

    PubMed

    Grande, Fedora; Tucci, Paola

    2016-01-01

    Titanium dioxide (TiO2) is a natural oxide of the element titanium with low toxicity, and negligible biological effects. The classification as bio-inert material has given the possibility to normal-sized (>100 nm) titanium dioxide particles (TiO2-NPs) to be extensively used in food products and as ingredients in a wide range of pharmaceutical products and cosmetics, such as sunscreens and toothpastes. Therefore, human exposure may occur through ingestion and dermal penetration, or through inhalation route, during both the manufacturing process and use. In spite of the extensively use of TiO2-NPs, the biological effects and the cellular response mechanisms are still not completely elucidated and thus a deep understanding of the toxicological profile of this compound is required. The main mechanism underlining the toxicity potentially triggered by TiO2-NPs seems to involve the reactive oxygen species (ROS) production, resulting in oxidative stress, inflammation, genotoxicity, metabolic change and potentially carcinogenesis. The extent and type of cell damage strongly depend on chemical and physical characteristics of TiO2-NPs, including size, crystal structure and photo-activation. In this mini-review, we would like to discuss the latest findings on the adverse effects and on potential human health risks induced by TiO2-NPs exposure.

  6. Control of the risk of human toxoplasmosis transmitted by meat.

    PubMed

    Kijlstra, Aize; Jongert, Erik

    2008-10-01

    One-third of the human world population is infected with the protozoan parasite Toxoplasma gondii. Recent calculations of the disease burden of toxoplasmosis rank this foodborne disease at the same level as salmonellosis or campylobacteriosis. The high disease burden in combination with disappointing results of the currently available treatment options have led to a plea for more effective prevention. In this review we describe Toxoplasma as a hazard associated with the consumption of undercooked meat or meat products and provide an analysis of the various options to control the risk of human toxoplasmosis via this source. Monitoring and surveillance programs may be implemented for pre-harvest control of Toxoplasma infection of farm animals, with the reduction of environmental oocyst load as the most important milestone. Alternatively, Toxoplasma safe meat can be obtained through simple post-harvest decontamination procedures, whereby freezing the meat may currently be the best option, although new technologies using irradiation or high-pressure treatment may offer promising alternatives. Influence of culture, religion and food handling customs may predispose a certain type of meat as an important source of infection, indicating that prevention needs to be tailored according to social habits in different regions in the world. The rationale for more stringent control measures to prevent toxoplasmosis both from disease and economic points of view is emphasized.

  7. Climate change and human health: present and future risks.

    PubMed

    McMichael, Anthony J; Woodruff, Rosalie E; Hales, Simon

    2006-03-11

    There is near unanimous scientific consensus that greenhouse gas emissions generated by human activity will change Earth's climate. The recent (globally averaged) warming by 0.5 degrees C is partly attributable to such anthropogenic emissions. Climate change will affect human health in many ways-mostly adversely. Here, we summarise the epidemiological evidence of how climate variations and trends affect various health outcomes. We assess the little evidence there is that recent global warming has already affected some health outcomes. We review the published estimates of future health effects of climate change over coming decades. Research so far has mostly focused on thermal stress, extreme weather events, and infectious diseases, with some attention to estimates of future regional food yields and hunger prevalence. An emerging broader approach addresses a wider spectrum of health risks due to the social, demographic, and economic disruptions of climate change. Evidence and anticipation of adverse health effects will strengthen the case for pre-emptive policies, and will also guide priorities for planned adaptive strategies.

  8. Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.

    PubMed

    Ukraintseva, Svetlana; Yashin, Anatoliy; Arbeev, Konstantin; Kulminski, Alexander; Akushevich, Igor; Wu, Deqing; Joshi, Gaurang; Land, Kenneth C; Stallard, Eric

    2016-02-01

    Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.

  9. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials.

    PubMed

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-03-02

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993.

  10. Comprehensive and Human Capital Crash Costs by Maximum Police-Reported Injury Severity Within Selected Crash Types

    PubMed Central

    Zaloshnja, Eduard; Miller, Ted; Council, Forrest; Persaud, Bhagwant

    2004-01-01

    This paper presents estimates for both the economic and comprehensive costs per crash for three police-coded severity groupings within 16 selected crash types and within two speed limit categories (<=45 and >=50 mph). The economic costs are hard dollar costs. The comprehensive costs include economic costs and quality of life losses. We merged previously developed costs per victim keyed on the Abbreviated Injury Scale (AIS) into US crash data files that scored injuries in both the AIS and police-coded severity scales to produce per crash estimates. The most costly crashes were non-intersection fatal/disabling injury crashes on a road with a speed limit of 50 miles per hour or higher where multiple vehicles crashed head-on or a single vehicle struck a human (over 1.69 and $1.16 million per crash, respectively). The annual cost of police-reported run-off-road collisions, which include both rollovers and object impacts, represented 34% of total costs. PMID:15319129

  11. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials

    PubMed Central

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-01-01

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993. PMID:26950143

  12. Human Error and Commercial Aviation Accidents: A Comprehensive, Fine-Grained Analysis Using HFACS

    DTIC Science & Technology

    2006-07-01

    recruited from the Oklahoma City area as subject-matter experts ( SMEs ). All were certified flight instructors with a minimum of 1,000 flight hours at...standing of specific terms, flight conditions, and the overall domain of aviation to be effectively classified and coded. As aviation SMEs , the pilot...the overall HFACS analysis of the commercial accident reports. Pilots, however, are not SMEs in the domain of psychol- ogy or human factors and may

  13. Multi-phase distribution and comprehensive ecological risk assessment of heavy metal pollutants in a river affected by acid mine drainage.

    PubMed

    Liao, Jianbo; Ru, Xuan; Xie, Binbin; Zhang, Wanhui; Wu, Haizhen; Wu, Chaofei; Wei, Chaohai

    2017-03-16

    To date, there is a lack of a comprehensive research on heavy metals detection and ecological risk assessment in river water, sediments, pore water (PW) and suspended solids (SS). Here, the concentrations of heavy metals, including Cu, Zn, Mn, Cd, Pb and As, and their distribution between the four phases was studied. Samples for analysis were taken from twelve sites of the Hengshi River, Guangdong Province, China, during the rainy and dry seasons. A new comprehensive ecological risk index (CERI) based on considering metal contents, pollution indices, toxicity coefficients and water categories is offered for prediction of potential risk on aquatic organisms. The results of comprehensive analysis showed that the highest concentrations of Cu, Zn and Mn of 6.42, 87.17 and 98.74mg/L, respectively, in PW were comparable with those in water, while concentrations of Cd, Pb and As of 609.5, 2757 and 96.38μg/L, respectively, were 2-5 times higher. The sum of the exchangeable and carbonate fractions of target metals in sediments followed the order of Cd > Mn > Zn > Pb > Cu > As. The distribution of heavy metals in phases followed the order of sediment > SS > water > PW, having the sum content in water and PW lower than 2% of total. The elevated ecological risk for a single metal and the phase were 34,585 for Cd and 1160 for water, respectively, implied Cd as a priority pollutant in the considered area. According to the CERI, the maximum risk value of 769.3 was smaller than 1160 in water, but higher than those in other phases. Out of considering the water categories and contribution coefficients, the CERI was proved to be more reliable for assessing the pollution of rivers with heavy metals. These results imply that the CERI has a potential of adequate assessment of multi-phase composite metals pollution.

  14. The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers.

    PubMed

    Amalric, Marie; Wang, Liping; Pica, Pierre; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

    2017-01-01

    During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a "geometrical language" with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them.

  15. Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers.

    PubMed

    Billing, Anja M; Ben Hamidane, Hisham; Dib, Shaima S; Cotton, Richard J; Bhagwat, Aditya M; Kumar, Pankaj; Hayat, Shahina; Yousri, Noha A; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

    2016-02-09

    Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.

  16. A comprehensive survey of non-canonical splice sites in the human transcriptome

    PubMed Central

    Parada, Guillermo E.; Munita, Roberto; Cerda, Cledi A.; Gysling, Katia

    2014-01-01

    We uncovered the diversity of non-canonical splice sites at the human transcriptome using deep transcriptome profiling. We mapped a total of 3.7 billion human RNA-seq reads and developed a set of stringent filters to avoid false non-canonical splice site detections. We identified 184 splice sites with non-canonical dinucleotides and U2/U12-like consensus sequences. We selected 10 of the herein identified U2/U12-like non-canonical splice site events and successfully validated 9 of them via reverse transcriptase-polymerase chain reaction and Sanger sequencing. Analyses of the 184 U2/U12-like non-canonical splice sites indicate that 51% of them are not annotated in GENCODE. In addition, 28% of them are conserved in mouse and 76% are involved in alternative splicing events, some of them with tissue-specific alternative splicing patterns. Interestingly, our analysis identified some U2/U12-like non-canonical splice sites that are converted into canonical splice sites by RNA A-to-I editing. Moreover, the U2/U12-like non-canonical splice sites have a differential distribution of splicing regulatory sequences, which may contribute to their recognition and regulation. Our analysis provides a high-confidence group of U2/U12-like non-canonical splice sites, which exhibit distinctive features among the total human splice sites. PMID:25123659

  17. Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers

    PubMed Central

    Billing, Anja M.; Ben Hamidane, Hisham; Dib, Shaima S.; Cotton, Richard J.; Bhagwat, Aditya M.; Kumar, Pankaj; Hayat, Shahina; Yousri, Noha A.; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

    2016-01-01

    Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC. PMID:26857143

  18. The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers

    PubMed Central

    Amalric, Marie; Wang, Liping; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

    2017-01-01

    During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a “geometrical language” with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them. PMID:28125595

  19. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    PubMed Central

    Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

  20. Strategies for human-driven robot comprehension of spatial descriptions by older adults in a robot fetch task.

    PubMed

    Carlson, Laura; Skubic, Marjorie; Miller, Jared; Huo, Zhiyu; Alexenko, Tatiana

    2014-07-01

    This contribution presents a corpus of spatial descriptions and describes the development of a human-driven spatial language robot system for their comprehension. The domain of application is an eldercare setting in which an assistive robot is asked to "fetch" an object for an elderly resident based on a natural language spatial description given by the resident. In Part One, we describe a corpus of naturally occurring descriptions elicited from a group of older adults within a virtual 3D home that simulates the eldercare setting. We contrast descriptions elicited when participants offered descriptions to a human versus robot avatar, and under instructions to tell the addressee how to find the target versus where the target is. We summarize the key features of the spatial descriptions, including their dynamic versus static nature and the perspective adopted by the speaker. In Part Two, we discuss critical cognitive and perceptual processing capabilities necessary for the robot to establish a common ground with the human user and perform the "fetch" task. Based on the collected corpus, we focus here on resolving the perspective ambiguity and recognizing furniture items used as landmarks in the descriptions. Taken together, the work presented here offers the key building blocks of a robust system that takes as input natural spatial language descriptions and produces commands that drive the robot to successfully fetch objects within our eldercare scenario.

  1. A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

    PubMed

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-02-01

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.

  2. Quality risk analysis in a cGMP environment: multiple models for comprehensive failure mode identification during the computer system lifecycle.

    PubMed

    Gervais, Brian; D'Arcy, Deirdre M

    2014-01-01

    Pharmaceutical quality systems use various inputs to ensure product quality and prevent failures that might have patient consequences. These inputs are generally data from failures that have already occurred, for example process deviations or customer complaints. Risk analysis techniques are well-established in certain other industries and have become of interest to pharmaceutical manufacturers because they allow potential quality failures to be predicted and mitigating action taken in advance of their occurring. Failure mode and effects analysis (FMEA) is one such technique, and in this study it was applied to implement a computerized manufacturing execution system in a pharmaceutical manufacturing environment. After introduction, the system was monitored to detect failures that did occur and these were analyzed to determine why the risk analysis method failed to predict them. Application of FMEA in other industries has identified weaknesses in predicting certain error types, specifically its dependence on other techniques to model risk situations and its poor analysis of non-hardware risks, such as human error, and this was confirmed in this study. Hierarchical holographic modeling (HHM), a technique for identifying risk scenarios in wide-scope analyses, was applied subsequently and identified additional potential failure modes. The technique for human error rate prediction (THERP) has previously been used for the quantitative analysis of human error risk and the event tree from this technique was adapted and identified further human error scenarios. These were input to the FMEA for prioritization and mitigation, thereby strengthening the risk analysis in terms of failure modes considered.

  3. The Human Papillomavirus and Its Role in Plantar Warts: A Comprehensive Review of Diagnosis and Management.

    PubMed

    Vlahovic, Tracey C; Khan, M Tariq

    2016-07-01

    Viral warts or verruca pedis (plantar warts) are common skin conditions seen in both children and adults. Human papilloma virus (HPV), a DNA virus, is responsible for plantar verrucae. It needs an epidermal abrasion and a transiently impaired immune system to inoculate a keratinocyte. These entities are a therapeutic conundrum for many practitioners. This article discusses HPV infiltration and its subtypes involved in plantar warts; the evaluation of patients with plantar warts; and subsequent treatment options, such as laser, Candida albicans immunotherapy, topical therapy such as phytotherapy, and surgical excision.

  4. A comprehensive framework to assess, model, and enhance the human role in conserving energy in commercial buildings

    NASA Astrophysics Data System (ADS)

    Azar, Elie

    Energy conservation and sustainability are subjects of great interest today, especially in the commercial building sector which is witnessing a very high and growing demand for energy. Traditionally, efforts to reduce energy consumption in this sector consisted of researching and developing energy efficient building technologies and systems. On the other hand, recent studies indicate that human actions are major determinants of building energy performance and can lead to excessive energy use even in advanced low-energy buildings. As a result, it is essential to determine if the approach to future energy reduction initiatives should remain solely technology-focused, or if a human-focused approach is also needed to complement advancements in technology and improve building operation and performance. In practice, while technology-focused solutions have been extensively researched, promoted, and adopted in commercial buildings, research efforts on the role of human actions and energy use behaviors in energy conservation remain very limited. This study fills the missing gap in literature by presenting a comprehensive framework to (1) understand and quantify the influence of human actions on building energy performance, (2) model building occupants' energy use behaviors and account for potential changes in these behaviors over time, and (3) test and optimize different human-focused energy reduction interventions to increase their adoption in commercial buildings. Results are significant and prove that human actions have a major role to play in reducing the energy intensity of the commercial building sector. This sheds the light on the need for a shift in how people currently use and control different buildings systems, as this is crucial to ensure efficient building operation and to maximize the return on investment in energy-efficient technologies. Furthermore, this study proposes methods and tools that can be applied on any individual or groups of commercial buildings

  5. Comprehensive Analysis of Low-Molecular-Weight Human Plasma Proteome Using Top-Down Mass Spectrometry.

    PubMed

    Cheon, Dong Huey; Nam, Eun Ji; Park, Kyu Hyung; Woo, Se Joon; Lee, Hye Jin; Kim, Hee Cheol; Yang, Eun Gyeong; Lee, Cheolju; Lee, Ji Eun

    2016-01-04

    While human plasma serves as a great source for disease diagnosis, low-molecular-weight (LMW) proteome (<30 kDa) has been shown to contain a rich source of diagnostic biomarkers. Here we employ top-down mass spectrometry to analyze the LMW proteoforms present in four types of human plasma samples pooled from three healthy controls (HCs) without immunoaffinity depletion and with depletion of the top two, six, and seven high-abundance proteins. The LMW proteoforms were first fractionated based on molecular weight using gel-eluted liquid fraction entrapment electrophoresis (GELFrEE). Then, the GELFrEE fractions containing up to 30 kDa were subjected to nanocapillary-LC-MS/MS, and the high-resolution MS and MS/MS data were processed using ProSightPC 3.0. As a result, a total of 442 LMW proteins and cleaved products, including those with post-translational modifications and single amino acid variations, were identified. From additional comparative analysis of plasma samples without immunoaffinity depletion between HCs and colorectal cancer (CRC) patients via top-down approach, tens of LMW proteoforms, including platelet factor 4, were found to show >1.5-fold changes between the plasma samples of HCs and CRC patients, and six of the LMW proteins were verified by Western blot analysis.

  6. GeneStoryTeller: a mobile app for quick and comprehensive information retrieval of human genes

    PubMed Central

    Eleftheriou, Stergiani V.; Bourdakou, Marilena M.; Athanasiadis, Emmanouil I.; Spyrou, George M.

    2015-01-01

    In the last few years, mobile devices such as smartphones and tablets have become an integral part of everyday life, due to their software/hardware rapid development, as well as the increased portability they offer. Nevertheless, up to now, only few Apps have been developed in the field of bioinformatics, capable to perform fast and robust access to services. We have developed the GeneStoryTeller, a mobile application for Android platforms, where users are able to instantly retrieve information regarding any recorded human gene, derived from eight publicly available databases, as a summary story. Complementary information regarding gene–drugs interactions, functional annotation and disease associations for each selected gene is also provided in the gene story. The most challenging part during the development of the GeneStoryTeller was to keep balance between storing data locally within the app and obtaining the updated content dynamically via a network connection. This was accomplished with the implementation of an administrative site where data are curated and synchronized with the application requiring a minimum human intervention. Database URL: http://bioserver-3.bioacademy.gr/Bioserver/GeneStoryTeller/. PMID:26055097

  7. Comprehensive Metabolomic and Lipidomic Profiling of Human Kidney Tissue: A Platform Comparison.

    PubMed

    Leuthold, Patrick; Schaeffeler, Elke; Winter, Stefan; Büttner, Florian; Hofmann, Ute; Mürdter, Thomas E; Rausch, Steffen; Sonntag, Denise; Wahrheit, Judith; Fend, Falko; Hennenlotter, Jörg; Bedke, Jens; Schwab, Matthias; Haag, Mathias

    2017-02-03

    Metabolite profiling of tissue samples is a promising approach for the characterization of cancer pathways and tumor classification based on metabolic features. Here, we present an analytical method for nontargeted metabolomics of kidney tissue. Capitalizing on different chemical properties of metabolites allowed us to extract a broad range of molecules covering small polar molecules and less polar lipid classes that were analyzed by LC-QTOF-MS after HILIC and RP chromatographic separation, respectively. More than 1000 features could be reproducibly extracted and analyzed (CV < 30%) in porcine and human kidney tissue, which were used as surrogate matrices for method development. To further assess assay performance, cross-validation of the nontargeted metabolomics platform to a targeted metabolomics approach was carried out. Strikingly, from 102 metabolites that could be detected on both platforms, the majority (>90%) revealed Spearman's correlation coefficients ≥0.3, indicating that quantitative results from the nontargeted assay are largely comparable to data derived from classical targeted assays. Finally, as proof of concept, the method was applied to human kidney tissue where a clear differentiation between kidney cancer and nontumorous material could be demonstrated on the basis of unsupervised statistical analysis.

  8. Influence of stearic acid on hemostatic risk factors in humans.

    PubMed

    Tholstrup, Tine

    2005-12-01

    Stearic acid has been claimed to be prothrombotic. Elevated plasma factor VII coagulant activity (FVIIc) may raise the risk of coronary thrombosis in the event of plaque rupture. Fibrinogen, an acute-phase protein, is necessary for normal blood clotting; however, elevated levels of fibrinogen increase the risk of coronary heart disease (CHD). Here I report the results of three controlled, human dietary intervention studies, which used a randomized crossover design to investigate the hemostatic effects of stearic acid-rich test diets in healthy young men. A diet high in stearic acid (shea butter) resulted in a 13% lower fasting plasma FVIIc than a high palmitic acid diet, and was 18% lower than a diet high in myristic and lauric acids (P = 0.001) after 3 wk of intervention. The stearic acid-rich test fat increased plasma fibrinogen concentrations slightly compared with the myristic-lauric acid diet (P < 0.01). When investigating the acute effects of fatty meals, those high in stearic acid (synthesized test fat) resulted in a smaller postprandial increase in FVII than those high in trans and oleic FA, indicating a smaller increase in activated FVII after ingesting stearic acid compared with fats high in monounsaturated FA, probably caused by lower postprandial lipemia. Thus, the present investigations did not find dietary stearic acid to be more thrombogenic, in either fasting effects compared with other long-chain FA, or in acute effects compared with dietary unsaturated FA, including trans monounsaturated FA. The slightly increased effect on fasting plasma fibrinogen may be biologically insignificant, but it should be investigated further.

  9. Estimated human health risks of disposing of nonhazardous oil field waste in salt caverns

    SciTech Connect

    Tomasko, D.; Elcock, D.; Veil, J.

    1997-09-01

    Argonne National Laboratory (ANL) has completed an evaluation of the possibility that adverse human health effects (carcinogenic and noncarcinogenic) could result from exposure to contaminants released from nonhazardous oil field wastes (NOW) disposed in domal salt caverns. In this assessment, several steps were used to evaluate potential human health risks: identifying potential contaminants of concern, determining how humans could be exposed to these contaminants, assessing the contaminants` toxicities, estimating contaminant intakes, and, finally, calculating human cancer and noncancer risks.

  10. [The care needs of women infected with the human papilloma virus: a comprehensive approach].

    PubMed

    Cestari, Maria Elisa Wotzasek; Merighi, Miriam Aparecida Barbosa; Garanhani, Mara Lúcia; Cardeli, Alexandrina Aparecida Maciel; de Jesus, Maria Cristina Pinto; Lopes, Dolores Ferreira de Melo

    2012-10-01

    This study is founded on the phenomenology of Martin Heidegger, with the objective to understand the care needs of women infected with the human papilloma virus. Participants were fourteen women who had been diagnosed with this infection. The guiding questions were: What is it like to have this diagnosis? Tell me your experience, from when you received your diagnosis until today. What has your health care been like? The questions revealed the theme - seeking care as solitude - which showed the importance of the support of family and friends. The presence of the infection as the cause of marital conflicts and separation was another highlighted aspect. The statements showed that there was a sense of resignation after an unsuccessful attempt to find accurate and clear information in order to make assertive decisions. Health interventions for infected women must overcome the traditional models of care, including interventions for health promotion and prevention, with trained professionals who are sensitive to the subjective dimension.

  11. Comprehensive Protocols for CRISPR/Cas9-based Gene Editing in Human Pluripotent Stem Cells.

    PubMed

    Santos, David P; Kiskinis, Evangelos; Eggan, Kevin; Merkle, Florian T

    2016-08-17

    Genome editing of human pluripotent stem cells (hPSCs) with the CRISPR/Cas9 system has the potential to revolutionize hPSC-based disease modeling, drug screening, and transplantation therapy. Here, we aim to provide a single resource to enable groups, even those with limited experience with hPSC culture or the CRISPR/Cas9 system, to successfully perform genome editing. The methods are presented in detail and are supported by a theoretical framework to allow for the incorporation of inevitable improvements in the rapidly evolving gene-editing field. We describe protocols to generate hPSC lines with gene-specific knock-outs, small targeted mutations, or knock-in reporters. © 2016 by John Wiley & Sons, Inc.

  12. Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

    PubMed

    Lieberman-Aiden, Erez; van Berkum, Nynke L; Williams, Louise; Imakaev, Maxim; Ragoczy, Tobias; Telling, Agnes; Amit, Ido; Lajoie, Bryan R; Sabo, Peter J; Dorschner, Michael O; Sandstrom, Richard; Bernstein, Bradley; Bender, M A; Groudine, Mark; Gnirke, Andreas; Stamatoyannopoulos, John; Mirny, Leonid A; Lander, Eric S; Dekker, Job

    2009-10-09

    We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  13. Inflammatory bowel diseases and human reproduction: A comprehensive evidence-based review

    PubMed Central

    Palomba, Stefano; Sereni, Giuliana; Falbo, Angela; Beltrami, Marina; Lombardini, Silvia; Boni, Maria Chiara; Fornaciari, Giovanni; Sassatelli, Romano; La Sala, Giovanni Battista

    2014-01-01

    To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines

  14. Comprehensive analysis of CpG islands in human chromosomes 21 and 22

    NASA Astrophysics Data System (ADS)

    Takai, Daiya; Jones, Peter A.

    2002-03-01

    CpG islands are useful markers for genes in organisms containing 5-methylcytosine in their genomes. In addition, CpG islands located in the promoter regions of genes can play important roles in gene silencing during processes such as X-chromosome inactivation, imprinting, and silencing of intragenomic parasites. The generally accepted definition of what constitutes a CpG island was proposed in 1987 by Gardiner-Garden and Frommer [Gardiner-Garden, M. & Frommer, M. (1987) J. Mol. Biol. 196, 261-282] as being a 200-bp stretch of DNA with a C+G content of 50% and an observed CpG/expected CpG in excess of 0.6. Any definition of a CpG island is somewhat arbitrary, and this one, which was derived before the sequencing of mammalian genomes, will include many sequences that are not necessarily associated with controlling regions of genes but rather are associated with intragenomic parasites. We have therefore used the complete genomic sequences of human chromosomes 21 and 22 to examine the properties of CpG islands in different sequence classes by using a search algorithm that we have developed. Regions of DNA of greater than 500 bp with a G+C equal to or greater than 55% and observed CpG/expected CpG of 0.65 were more likely to be associated with the 5' regions of genes and this definition excluded most Alu-repetitive elements. We also used genome sequences to show strong CpG suppression in the human genome and slight suppression in Drosophila melanogaster and Saccharomyces cerevisiae. This finding is compatible with the recent detection of 5-methylcytosine in Drosophila, and might suggest that S. cerevisiae has, or once had, CpG methylation.

  15. Comprehensive screening for antigens overexpressed on carcinomas via isolation of human mAbs that may be therapeutic

    PubMed Central

    Kurosawa, Gene; Akahori, Yasushi; Morita, Miwa; Sumitomo, Mariko; Sato, Noriko; Muramatsu, Chiho; Eguchi, Keiko; Matsuda, Kazuki; Takasaki, Akihiko; Tanaka, Miho; Iba, Yoshitaka; Hamada-Tsutsumi, Susumu; Ukai, Yoshinori; Shiraishi, Mamoru; Suzuki, Kazuhiro; Kurosawa, Maiko; Fujiyama, Sally; Takahashi, Nobuhiro; Kato, Ryoichi; Mizoguchi, Yoshikazu; Shamoto, Mikihiro; Tsuda, Hiroyuki; Sugiura, Mototaka; Hattori, Yoshinobu; Miyakawa, Shuichi; Shiroki, Ryoichi; Hoshinaga, Kiyotaka; Hayashi, Nobuhiro; Sugioka, Atsushi; Kurosawa, Yoshikazu

    2008-01-01

    Although several murine mAbs that have been humanized became useful therapeutic agents against a few malignancies, therapeutic Abs are not yet available for the majority of the human cancers because of our lack of knowledge of which antigens (Ags) can become useful targets. In the present study we established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may become therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of tumor cells. They were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by MS. We isolated 2,114 mAbs with unique sequences and identified 21 distinct Ags highly expressed on several carcinomas. Of those 2,114 mAbs 356 bound specifically to one of the 21 Ags. After preparing complete IgG1 Abs the in vitro assay for Ab-dependent cell-mediated cytotoxicity (ADCC) and the in vivo assay in cancer-bearing athymic mice were performed to examine antitumor activity. The mAbs converted to IgG1 revealed effective ADCC as well as antitumor activity in vivo. Because half of the 21 Ags showed distinct tumor-specific expression pattern and the mAbs isolated showed various characteristics with strong affinity to the Ag, it is likely that some of the Ags detected will become useful targets for the corresponding carcinoma therapy and that several mAbs will become therapeutic agents. PMID:18474866

  16. Human Research Program Human Health Countermeasures Element Extravehicular Activity (EVA) Risk Standing Review Panel (SRP)

    NASA Technical Reports Server (NTRS)

    Norfleet, William; Harris, Bernard

    2009-01-01

    The Extravehicular Activity (EVA) Risk Standing Review Panel (SRP) was favorably impressed by the operational risk management approach taken by the Human Research Program (HRP) Integrated Research Plan (IRP) to address the stated life sciences issues. The life sciences community at the Johnson Space Center (JSC) seems to be focused on operational risk management. This approach is more likely to provide risk managers with the information they need at the time they need it. Concerning the information provided to the SRP by the EVA Physiology, Systems, and Performance Project (EPSP), it is obvious that a great deal of productive activity is under way. Evaluation of this information was hampered by the fact that it often was not organized in a fashion that reflects the "Gaps and Tasks" approach of the overall Human Health Countermeasures (HHC) effort, and that a substantial proportion of the briefing concerned subjects that, while interesting, are not part of the HHC Element (e.g., the pressurized rover presentation). Additionally, no information was provided on several of the tasks or how they related to work underway or already accomplished. This situation left the SRP having to guess at the efforts and relationship to other elements, and made it hard to easily map the EVA Project efforts currently underway, and the data collected thus far, to the gaps and tasks in the IRP. It seems that integration of the EPSP project into the HHC Element could be improved. Along these lines, we were concerned that our SRP was split off from the other participating SRPs at an early stage in the overall agenda for the meeting. In reality, the concerns of EPSP and other projects share much common ground. For example, the commonality of the concerns of the EVA and exercise physiology groups is obvious, both in terms of what reduced exercise capacity can do to EVA capability, and how the exercise performed during an EVA could contribute to an overall exercise countermeasure prescription.

  17. Assessing the Risk of Antibiotic Resistance Transmission from the Environment to Humans: Non-Direct Proportionality between Abundance and Risk.

    PubMed

    Manaia, Célia M

    2017-03-01

    The past decade has witnessed a burst of study regarding antibiotic resistance in the environment, mainly in areas under anthropogenic influence. Therefore, impacts of the contaminant resistome, that is, those related to human activities, are now recognized. However, a key issue refers to the risk of transmission of resistance to humans, for which a quantitative model is urgently needed. This opinion paper makes an overview of some risk-determinant variables and raises questions regarding research needs. A major conclusion is that the risks of transmission of antibiotic resistance from the environment to humans must be managed under the precautionary principle, because it may be too late to act if we wait until we have concrete risk values.

  18. Negotiating new literacies in science: An examination of at-risk and average-achieving ninth-grade readers' online reading comprehension strategies

    NASA Astrophysics Data System (ADS)

    Sevensma, Kara

    In today's digital world the Internet is becoming an increasingly predominant resource for science information, rapidly eclipsing the traditional science textbook in content area classrooms (Lawless & Schrader, 2008). The shift challenges researchers, educators, administrators, and policy makers to reconsider what it means to read and comprehend online science information. The research on digital literacy is still in its infancy and little is known about the strategies and processes students use when reading science content on the Internet. Even less is known about how at-risk readers comprehend digital science content. Therefore, this study addresses three research questions: (1) What strategies and processes do at-risk and average-achieving readers use as they locate information and generate meaning from science websites? (2) What navigational profiles emerge as at-risk and average-achieving readers construct traversals (unique online paths of information) they locate information and generate meaning from science websites? (3) What individual characteristics influenced students' strategies as they locate information and generate meaning from science websites? Participants were six ninth-grade students in general education biology classrooms. Three were average-achieving readers and three were at-risk readers based on assessments of reading comprehension in traditional print-based texts. The students engaged in a three-day research project about the rainforest biome, locating information online, taking notes, and constructing an information brochure about the rainforest for peers. Data measures prior to and during the research included an Internet use survey, verbal protocols, screen captures of online activity, oral reading fluency assessments, and prior knowledge and topic engagement surveys. Quantitative descriptive and univariate analyses as well as qualitative abductive coding were employed over multiple phases to analyze the data. First, the results suggest

  19. The Effects of the Paraphrasing Strategy on the Reading Comprehension of Middle School Students at Risk for Failure in Reading

    ERIC Educational Resources Information Center

    Hagaman, Jessica L.; Reid, Robert

    2008-01-01

    Reading is an important component of academic success and a skill required for many adult responsibilities. Many strategies exist that claim to increase reading comprehension. However, in contrast to foundational reading skills (e.g., vocabulary, fluency, decoding), there is relatively little research that has been done on reading comprehension…

  20. A Comprehensive, Multi-Scale Dynamical Model of ErbB Receptor Signal Transduction in Human Mammary Epithelial Cells

    PubMed Central

    Helikar, Tomáš; Kochi, Naomi; Kowal, Bryan; Dimri, Manjari; Naramura, Mayumi; Raja, Srikumar M.; Band, Vimla; Band, Hamid; Rogers, Jim A.

    2013-01-01

    The non-receptor tyrosine kinase Src and receptor tyrosine kinase epidermal growth factor receptor (EGFR/ErbB1) have been established as collaborators in cellular signaling and their combined dysregulation plays key roles in human cancers, including breast cancer. In part due to the complexity of the biochemical network associated with the regulation of these proteins as well as their cellular functions, the role of Src in EGFR regulation remains unclear. Herein we present a new comprehensive, multi-scale dynamical model of ErbB receptor signal transduction in human mammary epithelial cells. This model, constructed manually from published biochemical literature, consists of 245 nodes representing proteins and their post-translational modifications sites, and over 1,000 biochemical interactions. Using computer simulations of the model, we find it is able to reproduce a number of cellular phenomena. Furthermore, the model predicts that overexpression of Src results in increased endocytosis of EGFR in the absence/low amount of the epidermal growth factor (EGF). Our subsequent laboratory experiments also suggest increased internalization of EGFR upon Src overexpression under EGF-deprived conditions, further supporting this model-generated hypothesis. PMID:23637902

  1. Are we ready to consider transgenerational epigenetic effects in human health risk assessment?

    PubMed

    Alyea, Rebecca A; Gollapudi, B Bhaskar; Rasoulpour, Reza J

    2014-04-01

    Recently, there has been a growing concern that chemically or nutritionally mediated epigenetic changes might lead to adverse health outcomes. The natural question is whether the existing chemical safety assessment paradigm is or is not protective of epigenetic-mediated effects, and if there is a need to incorporate new endpoints to specifically address epigenetics. Of particular interest are transgenerational epigenetic effects, which can be passed on through multiple generations. To investigate these questions, a comparison was performed between OECD guideline rat toxicology studies versus several rat transgenerational epigenetic studies. This analysis focused on vinclozolin owing to the availability of a comprehensive suite of dose-response data (NOAEL, reference dose, and human exposure estimates) for both conventional and epigenetic endpoints. This analysis revealed that vinclozolin transgenerational effects were demonstrated at a dose level (100 mg/kg/day) that was: (1) ∼40-fold higher than the overall lowest-observed-adverse-effect level (LOAEL) from rat guideline studies, (2) ∼80-fold higher than the lowest NOAEL from rat guideline studies, (3) ∼80,000-fold higher than the reference dose for the molecule, and (4) ∼1.2-million fold above human exposure estimates. Through this analysis, we conclude that additional research across a spectrum of doses is necessary to elucidate the interplay between epigenetics and apical endpoints before considering epigenetics in human health risk assessment. Therefore, we recommend focusing future research toward (1) examining for potential causal relationships between epigenetic alterations and adverse apical endpoints, and (2) understanding the dose-response relationship of these causal epigenetic alterations when compared with those of the apical endpoints.

  2. Comprehensive expression analysis suggests functional overlapping of human FOX transcription factors in cancer.

    PubMed

    Zhang, Ya-Li; Sun, Feng-Ting; Zhang, Ze; Chen, Xiao-Xu; Liu, Ai-Xiang; Pan, Jing-Jing; Peng, Fei; Zhou, Shuai; Sun, Li-Jun

    2014-01-01

    Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.

  3. Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression.

    PubMed

    Torrente, Aurora; Lukk, Margus; Xue, Vincent; Parkinson, Helen; Rung, Johan; Brazma, Alvis

    2016-01-01

    Rapid accumulation and availability of gene expression datasets in public repositories have enabled large-scale meta-analyses of combined data. The richness of cross-experiment data has provided new biological insights, including identification of new cancer genes. In this study, we compiled a human gene expression dataset from ∼40,000 publicly available Affymetrix HG-U133Plus2 arrays. After strict quality control and data normalisation the data was quantified in an expression matrix of ∼20,000 genes and ∼28,000 samples. To enable different ways of sample grouping, existing annotations where subjected to systematic ontology assisted categorisation and manual curation. Groups like normal tissues, neoplasmic tissues, cell lines, homoeotic cells and incompletely differentiated cells were created. Unsupervised analysis of the data confirmed global structure of expression consistent with earlier analysis but with more details revealed due to increased resolution. A suitable mixed-effects linear model was used to further investigate gene expression in solid tissue tumours, and to compare these with the respective healthy solid tissues. The analysis identified 1,285 genes with systematic expression change in cancer. The list is significantly enriched with known cancer genes from large, public, peer-reviewed databases, whereas the remaining ones are proposed as new cancer gene candidates. The compiled dataset is publicly available in the ArrayExpress Archive. It contains the most diverse collection of biological samples, making it the largest systematically annotated gene expression dataset of its kind in the public domain.

  4. Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs

    PubMed Central

    Zhou, Chenlin; Yang, Xiaoqin; Sun, Yiyang; Yu, Hongyao; Zhang, Yong; Jin, Ying

    2016-01-01

    SOX2 is a key regulator of multiple types of stem cells, especially embryonic stem cells (ESCs) and neural progenitor cells (NPCs). Understanding the mechanism underlying the function of SOX2 is of great importance for realizing the full potential of ESCs and NPCs. Here, through genome-wide comparative studies, we show that SOX2 executes its distinct functions in human ESCs (hESCs) and hESC-derived NPCs (hNPCs) through cell type- and stage-dependent transcription programs. Importantly, SOX2 suppresses non-neural lineages in hESCs and regulates neurogenesis from hNPCs by inhibiting canonical Wnt signaling. In hESCs, SOX2 achieves such inhibition by direct transcriptional regulation of important Wnt signaling modulators, WLS and SFRP2. Moreover, SOX2 ensures pluripotent epigenetic landscapes via interacting with histone variant H2A.Z and recruiting polycomb repressor complex 2 to poise developmental genes in hESCs. Together, our results advance our understanding of the mechanism by which cell type-specific transcription factors control lineage-specific gene expression programs and specify cell fate. PMID:26809499

  5. Comprehensive proteomic analysis of the human milk proteome: contribution of protein fractionation.

    PubMed

    Mangé, A; Bellet, V; Tuaillon, E; Van de Perre, P; Solassol, J

    2008-12-15

    In-depth analysis of the milk proteome by mass spectrometry is challenged by the presence of few high-abundance proteins that interfere with the detection of lower-abundance proteins. Here, we evaluated the proteomic analysis of milk samples following a strong anion exchange fractionation procedure using denaturating conditions ensuring the disruption of protein-protein interactions. Crude whey or skim milk and their different resulting fractions were analyzed by protein chip array mass spectrometry. Using protein chip array mass spectrometry, several high-abundance proteins were localized in distinct fractions increasing the total number of unique peptides and proteins detected. This total number increased by about 20-30% by combining different chromatographic surface arrays used for capture. Reproducible results were obtained in human skim milk and whey; however this approach was not successful with milk fat globule membrane and required refinement. Hence, milk profiling by anion exchange fractionation combined to protein chip array mass spectrometry represents a promising tool to detect unknown low-abundance milk proteins that may ultimately prove useful as biomarkers of diseases transmitted by breastfeeding.

  6. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE® Bone Graft)

    PubMed Central

    Peckham, Steven M.; Badura, Jeffrey M.

    2007-01-01

    The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS) carrier has been shown to induce bone formation in a number of preclinical and clinical investigations. In 2002, rhBMP-2/ACS at a 1.5-mg/cc concentration (INFUSE® Bone Graft, Medtronic Spinal and Biologics, Memphis, TN) was FDA-approved as an autograft replacement for certain interbody spinal fusion procedures. In 2004, INFUSE® Bone Graft was approved for open tibial fractures with an intermedullary (IM) nail fixation. Most recently, in March 2007, INFUSE® Bone Graft was approved as an alternative to autogenous bone grafts for sinus augmentations, and for localised alveolar ridge augmentations for defects associated with extraction sockets. The culmination of extensive preclinical and clinical research and three FDA approvals makes rhBMP-2 one of the most studied, published and significant advances in orthopaedics. This review article summarises a number of clinical findings of rhBMP-2/ACS, including the FDA-approved investigational device exemption (IDE) studies used in gaining the aforementioned approvals. PMID:17639384

  7. Effects of comprehensive cardiac rehabilitation on functional capacity and cardiovascular risk factors in Brazilians assisted by public health care: protocol for a randomized controlled trial

    PubMed Central

    Chaves, Gabriela S. S.; Ghisi, Gabriela L. M.; Grace, Sherry L.; Oh, Paul; Ribeiro, Antonio L.; Britto, Raquel R.

    2016-01-01

    ABSTRACT Background Cardiovascular Disease (CVD) is the leading burden of disease worldwide. Moreover, CVD-related death rates are considered an epidemic in low- and middle-income countries (LMICs). Research shows that cardiac rehabilitation (CR) participation reduces death and improves disability and quality of life. Given the growing epidemic of CVD in LMICs and the insufficient evidence about CR programs in these countries, a Randomized Control Trial (RCT) in Latin America is warranted. Objective To investigate the effects of comprehensive CR on functional capacity and cardiovascular risk factors. Method The design is a single-blinded RCT with three parallel arms: comprehensive CR (exercise + education) versus exercise-based CR versus wait-list control (no CR). The primary outcome will be measured by the Incremental Shuttle Walk Test. Secondary outcomes are risk factors (blood pressure, dyslipidemia, dysglycemia, body mass index and waist circumference); tertiary outcomes are heart health behaviors (exercise, medication adherence, diet, and smoking), knowledge, and depressive symptoms. The CR program is six months in duration. Participants randomized to exercise-based CR will receive 24 weeks of exercise classes. The comprehensive CR group will also receive 24 educational sessions, including a workbook. Every outcome will be assessed at baseline and 6-months later, and mortality will be ascertained at six months and one year. Conclusion This will be the first RCT to establish the effects of CR in Latin America. If positive, results will be used to promote broader implementation of comprehensive CR and patient access in the region and to inform a larger-scale trial powered for mortality. PMID:27849287

  8. MEASURING RISKS IN HUMANS: THE PROMISE AND PRACTICE OF EPIDEMIOLOGY

    EPA Science Inventory


    Epidemiology has been considered the fundamental science of public health policy. The use of epidemiologic data in environmental health policy has been limited particularly in the environmental regulatory arena. Epidemiologic risk assessment (ERA) is different from risk ass...

  9. Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression

    PubMed Central

    Lukk, Margus; Xue, Vincent; Parkinson, Helen; Rung, Johan; Brazma, Alvis

    2016-01-01

    Rapid accumulation and availability of gene expression datasets in public repositories have enabled large-scale meta-analyses of combined data. The richness of cross-experiment data has provided new biological insights, including identification of new cancer genes. In this study, we compiled a human gene expression dataset from ∼40,000 publicly available Affymetrix HG-U133Plus2 arrays. After strict quality control and data normalisation the data was quantified in an expression matrix of ∼20,000 genes and ∼28,000 samples. To enable different ways of sample grouping, existing annotations where subjected to systematic ontology assisted categorisation and manual curation. Groups like normal tissues, neoplasmic tissues, cell lines, homoeotic cells and incompletely differentiated cells were created. Unsupervised analysis of the data confirmed global structure of expression consistent with earlier analysis but with more details revealed due to increased resolution. A suitable mixed-effects linear model was used to further investigate gene expression in solid tissue tumours, and to compare these with the respective healthy solid tissues. The analysis identified 1,285 genes with systematic expression change in cancer. The list is significantly enriched with known cancer genes from large, public, peer-reviewed databases, whereas the remaining ones are proposed as new cancer gene candidates. The compiled dataset is publicly available in the ArrayExpress Archive. It contains the most diverse collection of biological samples, making it the largest systematically annotated gene expression dataset of its kind in the public domain. PMID:27322383

  10. Conceptual Model of Comprehensive Research Metrics for Improved Human Health and Environment

    PubMed Central

    Engel-Cox, Jill A.; Van Houten, Bennett; Phelps, Jerry; Rose, Shyanika W.

    2008-01-01

    Objective Federal, state, and private research agencies and organizations have faced increasing administrative and public demand for performance measurement. Historically, performance measurement predominantly consisted of near-term outputs measured through bibliometrics. The recent focus is on accountability for investment based on long-term outcomes. Developing measurable outcome-based metrics for research programs has been particularly challenging, because of difficulty linking research results to spatially and temporally distant outcomes. Our objective in this review is to build a logic model and associated metrics through which to measure the contribution of environmental health research programs to improvements in human health, the environment, and the economy. Data sources We used expert input and literature research on research impact assessment. Data extraction With these sources, we developed a logic model that defines the components and linkages between extramural environmental health research grant programs and the outputs and outcomes related to health and social welfare, environmental quality and sustainability, economics, and quality of life. Data synthesis The logic model focuses on the environmental health research portfolio of the National Institute of Environmental Health Sciences (NIEHS) Division of Extramural Research and Training. The model delineates pathways for contributions by five types of institutional partners in the research process: NIEHS, other government (federal, state, and local) agencies, grantee institutions, business and industry, and community partners. Conclusions The model is being applied to specific NIEHS research applications and the broader research community. We briefly discuss two examples and discuss the strengths and limits of outcome-based evaluation of research programs. PMID:18470312

  11. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    PubMed

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation.

  12. Predictive Mapping of Human Risk for West Nile Virus (WNV) Based on Environmental and Socioeconomic Factors

    PubMed Central

    Rochlin, Ilia; Turbow, David; Gomez, Frank; Ninivaggi, Dominick V.; Campbell, Scott R.

    2011-01-01

    A West Nile virus (WNV) human risk map was developed for Suffolk County, New York utilizing a case-control approach to explore the association between the risk of vector-borne WNV and habitat, landscape, virus activity, and socioeconomic variables derived from publically available datasets. Results of logistic regression modeling for the time period between 2000 and 2004 revealed that higher proportion of population with college education, increased habitat fragmentation, and proximity to WNV positive mosquito pools were strongly associated with WNV human risk. Similar to previous investigations from north-central US, this study identified middle class suburban neighborhoods as the areas with the highest WNV human risk. These results contrast with similar studies from the southern and western US, where the highest WNV risk was associated with low income areas. This discrepancy may be due to regional differences in vector ecology, urban environment, or human behavior. Geographic Information Systems (GIS) analytical tools were used to integrate the risk factors in the 2000–2004 logistic regression model generating WNV human risk map. In 2005–2010, 41 out of 46 (89%) of WNV human cases occurred either inside of (30 cases) or in close proximity (11 cases) to the WNV high risk areas predicted by the 2000–2004 model. The novel approach employed by this study may be implemented by other municipal, local, or state public health agencies to improve geographic risk estimates for vector-borne diseases based on a small number of acute human cases. PMID:21853103

  13. Predictive mapping of human risk for West Nile virus (WNV) based on environmental and socioeconomic factors.

    PubMed

    Rochlin, Ilia; Turbow, David; Gomez, Frank; Ninivaggi, Dominick V; Campbell, Scott R

    2011-01-01

    A West Nile virus (WNV) human risk map was developed for Suffolk County, New York utilizing a case-control approach to explore the association between the risk of vector-borne WNV and habitat, landscape, virus activity, and socioeconomic variables derived from publically available datasets. Results of logistic regression modeling for the time period between 2000 and 2004 revealed that higher proportion of population with college education, increased habitat fragmentation, and proximity to WNV positive mosquito pools were strongly associated with WNV human risk. Similar to previous investigations from north-central US, this study identified middle class suburban neighborhoods as the areas with the highest WNV human risk. These results contrast with similar studies from the southern and western US, where the highest WNV risk was associated with low income areas. This discrepancy may be due to regional differences in vector ecology, urban environment, or human behavior. Geographic Information Systems (GIS) analytical tools were used to integrate the risk factors in the 2000-2004 logistic regression model generating WNV human risk map. In 2005-2010, 41 out of 46 (89%) of WNV human cases occurred either inside of (30 cases) or in close proximity (11 cases) to the WNV high risk areas predicted by the 2000-2004 model. The novel approach employed by this study may be implemented by other municipal, local, or state public health agencies to improve geographic risk estimates for vector-borne diseases based on a small number of acute human cases.

  14. A Comprehensive Proteomic View of Responses of A549 Type II Alveolar Epithelial Cells to Human Respiratory Syncytial Virus Infection*

    PubMed Central

    Dave, Keyur A.; Norris, Emma L.; Bukreyev, Alexander A.; Headlam, Madeleine J.; Buchholz, Ursula J.; Singh, Toshna; Collins, Peter L.; Gorman, Jeffrey J.

    2014-01-01

    Human respiratory syncytial virus is a major respiratory pathogen for which there are no suitable antivirals or vaccines. A better understanding of the host cell response to this virus may redress this problem. The present report concerns analysis of multiple independent biological replicates of control and 24 h infected lysates of A549 cells by two different proteomic workflows. One workflow involved fractionation of lysates by in-solution protein IEF and individual fractions were digested using trypsin prior to capillary HPLC-LTQ-OrbitrapXL-MS/MS. A second workflow involved digestion of whole cell lysates and analysis by nanoUltraHPLC-LTQ-OrbitrapElite-MS/MS. Both workflows resulted in the quantification of viral proteins exclusively in lysates of infected cells in the relative abundances anticipated from previous studies. Unprecedented numbers (3247 - 5010) of host cell protein groups were also quantified and the infection-specific regulation of a large number (191) of these protein groups was evident based on a stringent false discovery rate cut-off (<1%). Bioinformatic analyses revealed that most of the regulated proteins were potentially regulated by type I, II, and III interferon, TNF-α and noncanonical NF-κB2 mediated antiviral response pathways. Regulation of specific protein groups by infection was validated by quantitative Western blotting and the cytokine-/key regulator-specific nature of their regulation was confirmed by comparable analyses of cytokine treated A549 cells. Overall, it is evident that the workflows described herein have produced the most comprehensive proteomic characterization of host cell responses to human respiratory syncytial virus published to date. These workflows will form the basis for analysis of the impacts of specific genes of human respiratory syncytial virus responses of A549 and other cell lines using a gene-deleted version of the virus. They should also prove valuable for the analysis of the impact of other infectious

  15. A comprehensive proteomic view of responses of A549 type II alveolar epithelial cells to human respiratory syncytial virus infection.

    PubMed

    Dave, Keyur A; Norris, Emma L; Bukreyev, Alexander A; Headlam, Madeleine J; Buchholz, Ursula J; Singh, Toshna; Collins, Peter L; Gorman, Jeffrey J

    2014-12-01

    Human respiratory syncytial virus is a major respiratory pathogen for which there are no suitable antivirals or vaccines. A better understanding of the host cell response to this virus may redress this problem. The present report concerns analysis of multiple independent biological replicates of control and 24 h infected lysates of A549 cells by two different proteomic workflows. One workflow involved fractionation of lysates by in-solution protein IEF and individual fractions were digested using trypsin prior to capillary HPLC-LTQ-OrbitrapXL-MS/MS. A second workflow involved digestion of whole cell lysates and analysis by nanoUltraHPLC-LTQ-OrbitrapElite-MS/MS. Both workflows resulted in the quantification of viral proteins exclusively in lysates of infected cells in the relative abundances anticipated from previous studies. Unprecedented numbers (3247 - 5010) of host cell protein groups were also quantified and the infection-specific regulation of a large number (191) of these protein groups was evident based on a stringent false discovery rate cut-off (<1%). Bioinformatic analyses revealed that most of the regulated proteins were potentially regulated by type I, II, and III interferon, TNF-α and noncanonical NF-κB2 mediated antiviral response pathways. Regulation of specific protein groups by infection was validated by quantitative Western blotting and the cytokine-/key regulator-specific nature of their regulation was confirmed by comparable analyses of cytokine treated A549 cells. Overall, it is evident that the workflows described herein have produced the most comprehensive proteomic characterization of host cell responses to human respiratory syncytial virus published to date. These workflows will form the basis for analysis of the impacts of specific genes of human respiratory syncytial virus responses of A549 and other cell lines using a gene-deleted version of the virus. They should also prove valuable for the analysis of the impact of other infectious

  16. The effect of a comprehensive lifestyle intervention on cardiovascular risk factors in pharmacologically treated patients with stable cardiovascular disease compared to usual care: a randomised controlled trial

    PubMed Central

    2012-01-01

    Background The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established. The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD) compared with usual care. Methods A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71) or control group (n = 75) using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication. Results The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference). In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor. Conclusions Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive lifestyle intervention had a

  17. On the evolution of hoarding, risk-taking, and wealth distribution in nonhuman and human populations

    PubMed Central

    Bergstrom, Theodore C.

    2014-01-01

    This paper applies the theory of the evolution of risk-taking in the presence of idiosyncratic and environmental risks to the example of food hoarding by animals and explores implications of the resulting theory for human attitudes toward risk. PMID:25024179

  18. A Stochastic Approach To Human Health Risk Assessment Due To Groundwater Contamination

    NASA Astrophysics Data System (ADS)

    de Barros, F. P.; Rubin, Y.

    2006-12-01

    We present a probabilistic framework to addressing adverse human health effects due to groundwater contamination. One of the main challenges in health risk assessment is in relating it to subsurface data acquisition and to improvement in our understanding of human physiological responses to contamination. In this paper we propose to investigate this problem through an approach that integrates flow, transport and human health risk models with hydrogeological characterization. A human health risk cumulative distribution function is analytically developed to account for both uncertainty and variability in hydrogeological as well as human physiological parameters. With our proposed approach, we investigate under which conditions the reduction of uncertainties from flow physics, human physiology and exposure related parameters might contribute to a better understanding of human health risk assessment. Results indicate that the human health risk cumulative distribution function is sensitive to physiological parameters at low risk values associated with longer travel times. The results show that the worth of hydrogeological characterization in human health risk is dependent on the residence time of the contaminant plume in the aquifer and on the exposure duration of the population to certain chemicals.

  19. Risk, Protection, and Achievement Disparities among African American Males: Cross-Generation Theory, Research, and Comprehensive Intervention

    ERIC Educational Resources Information Center

    Rowley, Larry L.; Bowman, Phillip J.

    2009-01-01

    In this post-industrial global society, parental and student role strains may exacerbate social-ecological risks and academic difficulties of African American male students. Therefore, school-based interventions must ensure rigorous preparation, promote successful navigation of social-ecological risks, and mobilize cultural-ecological strengths to…

  20. 78 FR 61365 - Assessment of the Risk of Human Salmonellosis Associated With the Consumption of Tree Nuts...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... HUMAN SERVICES Food and Drug Administration Assessment of the Risk of Human Salmonellosis Associated... entitled ``Assessment of the Risk of Human Salmonellosis Associated With the Consumption of Tree Nuts... of the risk of human salmonellosis associated with the consumption of tree nuts. We are taking...

  1. Estimating risk at a Superfund site using passive sampling devices as biological surrogates in human health risk models.

    PubMed

    Allan, Sarah E; Sower, Gregory J; Anderson, Kim A

    2011-10-01

    Passive sampling devices (PSDs) sequester the freely dissolved fraction of lipophilic contaminants, mimicking passive chemical uptake and accumulation by biomembranes and lipid tissues. Public Health Assessments that inform the public about health risks from exposure to contaminants through consumption of resident fish are generally based on tissue data, which can be difficult to obtain and requires destructive sampling. The purpose of this study is to apply PSD data in a Public Health Assessment to demonstrate that PSDs can be used as a biological surrogate to evaluate potential human health risks and elucidate spatio-temporal variations in risk. PSDs were used to measure polycyclic aromatic hydrocarbons (PAHs) in the Willamette River; upriver, downriver and within the Portland Harbor Superfund megasite for 3 years during wet and dry seasons. Based on an existing Public Health Assessment for this area, concentrations of PAHs in PSDs were substituted for fish tissue concentrations. PSD measured PAH concentrations captured the magnitude, range and variability of PAH concentrations reported for fish/shellfish from Portland Harbor. Using PSD results in place of fish data revealed an unacceptable risk level for cancer in all seasons but no unacceptable risk for non-cancer endpoints. Estimated cancer risk varied by several orders of magnitude based on season and location. Sites near coal tar contamination demonstrated the highest risk, particularly during the dry season and remediation activities. Incorporating PSD data into Public Health Assessments provides specific spatial and temporal contaminant exposure information that can assist public health professionals in evaluating human health risks.

  2. Why do residential recycled water schemes fail? A comprehensive review of risk factors and impact on objectives.

    PubMed

    West, Camilla; Kenway, Steven; Hassall, Maureen; Yuan, Zhiguo

    2016-10-01

    In Australia, recycled water schemes have been implemented in residential developments to contribute to sustainable urban development, improve water supply security and reduce pollutant discharges to the environment. A proportion of these schemes, however, have been decommissioned well before the end of their design life which raises questions about the adequacy of the risk assessment and management practices adopted for recycled water schemes. Through a detailed literature review, an investigation of 21 residential recycled water schemes and in-depth interviews with nine scheme stakeholders, we identified 34 risk factors arising from six sources which have the potential to impact the long-term viability of residential recycled water schemes. Of the 34 risk factors identified, 17 were reported to have occurred during the development and implementation of the 21 schemes investigated. The overall risk rating of the 17 factors was qualitatively defined on the basis of the likelihood of occurrence and the impact of the risk factors on the scheme objectives. The outcomes of the assessment indicate that the critical risks to the long-term viability of residential recycled water schemes are 1. unanticipated operational costs, 2. legal and contractual arrangements, 3. regulatory requirements and approval process and 4. customer complaints and expectations not met. To date, public health risks associated with the provision of recycled water have been of primary concern, though the outcomes of this study indicate that the impact to public health has been low. Evidently there is a need for improved assessment and management practices which address the range of critical risk factors, in addition to the routine consideration of public health risks.

  3. The Comprehensive Child Development Centers Act. Report from the Committee on Labor and Human Resources (To Accompany S. 1542). 100th Congress, 1st Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    This report of the Committee on Labor and Human Resources recommends that the Senate pass the Comprehensive Child Development Centers Act of 1987, S. 1542. The bill amends the Head Start Act to provide for the establishment of several child development centers designed to encourage supportive services for infants and young children from low income…

  4. Moving from viral suppression to comprehensive patient-centered care: the high prevalence of comorbid conditions and health risk factors in HIV-1-infected patients in Australia.

    PubMed

    Broom, Jennifer; Sowden, David; Williams, Merran; Taing, Kuong; Morwood, Karen; McGill, Karen

    2012-01-01

    HIV clinicians today need to move from focusing on viral suppression to a chronic disease model in which comorbid conditions and risk factors are comprehensively identified and addressed to reduce rates of serious non-AIDS-related morbidity and mortality. This study aimed to determine the prevalence of comorbid conditions in an Australian HIV-positive population. Of 180 patients included, there was a median CD4 count of 0.520 cells/mm(3). The majority (88%) of patients were currently receiving highly active antiretroviral therapy (HAART). There were high rates of failure to attend clinical appointments (30%), current smoking (42%), hypertension (16%), and dyslipidemia (17%). Significant rates of dipstick-positive proteinuria (16%) and elevated blood glucose (15%) were recorded. Risk factors were commonly not addressed by the treating clinician. There is an urgent need to systematize detection and management of high-prevalence comorbid conditions to prevent premature mortality associated with serious non-AIDS events.

  5. Assessment of regional human health risks from lead contamination in Yunnan province, southwestern China.

    PubMed

    Lu, Lu; Cheng, Hongguang; Liu, Xuelian; Xie, Jing; Li, Qian; Zhou, Tan

    2015-01-01

    Identification and management the 'critical risk areas' where hotspot lead exposures are a potential risk to human health, become a major focus of public health efforts in China. But the knowledge of health risk assessment of lead pollution at regional and national scales is still limited in China. In this paper, under the guidance of 'sources-pathways-receptors' framework, regional human health risk assessment model for lead contamination was developed to calculate the population health risk in Yunnan province. And the cluster and AHP (analytic hierarchy process) analysis was taken to classify and calculate regional health risk and the decomposition of the regional health risk in the greatest health risk region, respectively. The results showed that Yunnan province can be divided into three areas. The highest health risk levels, located in northeastern Yunnan, including Kunming, Qujing, Zhaotong region. In those regions, lead is present at high levels in air, food, water and soil, and high population density which pose a high potential population risk to the public. The current study also reveals that most regional health risk was derived from the child receptors (age above 3 years) 4.3 times than the child receptors (age under 3 years), and ingestion of lead-contaminated rice was found to be the most significant contributor to the health risk (accounting for more than 49% health risk of total). This study can provide a framework for regional risk assessment in China and highlighted some indicators and uncertainties.

  6. Comprehensive and quantitative proteomic analyses of zebrafish plasma reveals conserved protein profiles between genders and between zebrafish and human.

    PubMed

    Li, Caixia; Tan, Xing Fei; Lim, Teck Kwang; Lin, Qingsong; Gong, Zhiyuan

    2016-04-13

    Omic approaches have been increasingly used in the zebrafish model for holistic understanding of molecular events and mechanisms of tissue functions. However, plasma is rarely used for omic profiling because of the technical challenges in collecting sufficient blood. In this study, we employed two mass spectrometric (MS) approaches for a comprehensive characterization of zebrafish plasma proteome, i.e. conventional shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) for an overview study and quantitative SWATH (Sequential Window Acquisition of all THeoretical fragment-ion spectra) for comparison between genders. 959 proteins were identified in the shotgun profiling with estimated concentrations spanning almost five orders of magnitudes. Other than the presence of a few highly abundant female egg yolk precursor proteins (vitellogenins), the proteomic profiles of male and female plasmas were very similar in both number and abundance and there were basically no other highly gender-biased proteins. The types of plasma proteins based on IPA (Ingenuity Pathway Analysis) classification and tissue sources of production were also very similar. Furthermore, the zebrafish plasma proteome shares significant similarities with human plasma proteome, in particular in top abundant proteins including apolipoproteins and complements. Thus, the current study provided a valuable dataset for future evaluation of plasma proteins in zebrafish.

  7. Comprehensive Sequence Analysis of the Human IL23A Gene Defines New Variation Content and High Rate of Evolutionary Conservation

    PubMed Central

    Tindall, Elizabeth A.; Hayes, Vanessa M.

    2010-01-01

    A newly described heterodimeric cytokine, interleukin-23 (IL-23) is emerging as a key player in both the innate and the adaptive T helper (Th)17 driven immune response as well as an initiator of several autoimmune diseases. The rate-limiting element of IL-23 production is believed to be driven by expression of the unique p19 subunit encoded by IL23A. We set out to perform comprehensive DNA sequencing of this previously under-studied gene in 96 individuals from two evolutionary distinct human population groups, Southern African Bantu and European. We observed a total of 33 different DNA variants within these two groups, 22 (67%) of which are currently not reported in any available database. We further demonstrate both inter-population and intra-species sequence conservation within the coding and known regulatory regions of IL23A, supporting a critical physiological role for IL-23. We conclude that IL23A may have undergone positive selection pressure directed towards conservation, suggesting that functional genetic variants within IL23A will have a significant impact on the host immune response. PMID:20154336

  8. A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice

    PubMed Central

    Maupin, Kevin A.; Droscha, Casey J.; Williams, Bart O.

    2013-01-01

    The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001–2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 (LRP5), was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma (OPPG). OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 (G171V) develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone. PMID:26273492

  9. Nanoparticle pollution and associated increasing potential risks on environment and human health: a case study of China.

    PubMed

    Gao, Yang; Yang, Tiantian; Jin, Jin

    2015-12-01

    The aims of this study are (1) to discuss the mechanism of nanoparticle lifecycle and estimate the impacts of its associated pollution on environment and human health; and (2) to provide recommendation to policy makers on how to leverage nanopollution and human health along with the rapid development of economics in China. Manufactured nanoparticles (MNPs) could either directly or indirectly impair human health and the environment. Exposures to MNP include many ways, such as via inhalation, ingestion, direct contact, or the use of consumer products over the lifecycle of the product. In China, the number of people exposed to MNP has been increasing year by year. To better provide medical care to people exposed to MNP, the Chinese government has established many disease control and prevention centers over China. However, the existing facilities and resources for controlling MNP are still not enough considering the number of people impacted by MNP and the number of ordinary workers in the MNP related industry applying for their occupational identification through the Center for Disease Control and Prevention. China should assess the apparent risk environment and human health being exposed to MNP and develop action plans to reduce the possibility of direct contacts between human beings and the emerging nanomaterials. In addition, we suggest more comprehensive studies on the MNP behavior and the development of quantitative approaches to measure MNP transport, and persistence should be carried out.

  10. Human Health Risk Implications of Multiple Sources of Faecal Indicator Bacteria in a Recreational Waterbody

    EPA Science Inventory

    We evaluate the influence of multiple sources of faecal indicator bacteria in recreational water bodies on potential human health risk by considering waters impacted by human and animal sources, human and non-pathogenic sources, and animal and non-pathogenic sources. We illustrat...

  11. NASA's human system risk management approach and its applicability to commercial spaceflight.

    PubMed

    Law, Jennifer; Mathers, Charles H; Fondy, Susan R E; Vanderploeg, James M; Kerstman, Eric L

    2013-01-01

    As planning continues for commercial spaceflight, attention is turned to NASA to assess whether its human system risk management approach can be applied to mitigate the risks associated with commercial suborbital and orbital flights. NASA uses a variety of methods to assess the risks to the human system based on their likelihood and consequences. In this article, we review these methods and categorize the risks in the system as "definite," "possible," or "least" concern for commercial spaceflight. As with career astronauts, these risks will be primarily mitigated by screening and environmental control. Despite its focus on long-duration exploration missions, NASA's human system risk management approach can serve as a preliminary knowledge base to help medical planners prepare for commercial spaceflights.

  12. Risk factors and preventive strategies for post-operative pancreatic fistula after pancreatic surgery: a comprehensive review

    PubMed Central

    Søreide, Kjetil; Labori, Knut Jørgen

    2016-01-01

    Abstract Background: Pancreas surgery has developed into a fairly safe procedure in terms of mortality, but is still hampered by considerable morbidity. Among the most frequent and dreaded complications are the development of a post-operative pancreatic fistula (POPF). The prediction and prevention of POPF remains an area of debate with several questions yet to be firmly addressed with solid answers. Methods: A systematic review of systematic reviews/meta-analyses and randomized trials in the English literature (PubMed/MEDLINE, Cochrane library, EMBASE) covering January 2005 to December 2015 on risk factors and preventive strategies for POPF. Results: A total of 49 systematic reviews and meta-analyses over the past decade discussed patient, surgeon, pancreatic disease and intraoperative related factors of POPF. Non-modifiable factors (age, BMI, comorbidity) and pathology (histotype, gland texture, duct size) that indicates surgery are associated with POPF risk. Consideration of anastomotic technique and use of somatostatin-analogs may slightly modify the risk of fistula. Sealant products appear to have no effect. Perioperative bleeding and transfusion enhance risk, but is modifiable by focus on technique and training. Drains may not prevent fistulae, but may help in early detection. Early drain-amylase may aid in detection. Predictive scores lack uniform validation, but may have a role in patient information if reliable pre-operative risk factors can be obtained. Conclusions: Development of POPF occurs through several demonstrated risk factors. Anastomotic technique and use of somatostatin-analogs may slightly decrease risk. Drains may aid in early detection of leaks, but do not prevent POPF. PMID:27216233

  13. Critical review of methods for risk ranking of food related hazards, based on risks for human health.

    PubMed

    van der Fels-Klerx, H J; van Asselt, E D; Raley, M; Poulsen, M; Korsgaard, H; Bredsdorff, L; Nauta, M; D'Agostino, M; Coles, D; Marvin, H J P; Frewer, L J

    2016-02-08

    This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered - based on their characteristics - into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years, multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided.

  14. Simulating the Risk of Investment in Human Capital

    ERIC Educational Resources Information Center

    Hartog, Joop; Van Ophem, Hans; Bajdechi, Simona Maria

    2007-01-01

    The risk of investment in schooling has largely been ignored. We mimic the investment decision facing a student and simulate risky earnings profiles in alternative options, with parameters taken from the very limited evidence. The distribution of rates of return appears positively skewed. Our best estimate of "ex ante" risk in university education…

  15. Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial

    PubMed Central

    Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai

    2016-01-01

    abstract Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6–36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile. PMID:26837471

  16. Human Adenovirus 36 Infection Increased the Risk of Obesity

    PubMed Central

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-01-01

    Abstract Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses. We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed. Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P < 0.001) with a high heterogeneity (I2 = 80.1%; P < 0.001) estimated by the random effect model. Subgroup analysis demonstrated that the pooled OR of HAdV-36 infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P < 0.001) in the adults and children, respectively. Compared to the HAdV-36 negative subjects, the SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: −0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I2 = 86.5%; P < 0.001). The BMI z-score in the children with HAdV-36 infection was higher than those without HAdV-36 infection (SMD = 0

  17. Low Back Pain in Athletes Is Associated with General and Sport Specific Risk Factors: A Comprehensive Review of Longitudinal Studies

    PubMed Central

    Moradi, Vahideh; Memari, Amir-Hossein; ShayestehFar, Monir; Kordi, Ramin

    2015-01-01

    We aimed to examine systematically the available evidence on risk factors of low back pain (LBP) in athletes. We performed search without language restriction in PubMed, Ovid, Google Scholar, Scopus, and CINAHL. Longitudinal studies that examined possible risk factors of LBP in athletes were included in this systematic review. Based on methodological quality of studies, a best-evidence synthesis was conducted. Seven longitudinal studies were included, four of which had high methodological quality. Results showed that previous LBP, decreased lumbar flexion, and decreased lumbar extension are positively associated with LBP. There was moderate evidence for hip flexor tightness and high body weight as a risk factor. We found insufficient evidence for association between forward bending, previous injury, and amount of training per week, active years, age, and sex with LBP. In conclusion this study would provide a list of risk factors for LBP in athletes, though it showed a strong evidence for only a few including decrease lumbar flexion or extension, previous LBP, and high body weight. This review indicated a high heterogeneity of study characteristics including assessed risk factors and statistical techniques might limit the quality of evidence. PMID:26783465

  18. A model for assessing the risk of human trafficking on a local level

    NASA Astrophysics Data System (ADS)

    Colegrove, Amanda

    Human trafficking is a human rights violation that is difficult to quantify. Models for estimating the number of victims of trafficking presented by previous researchers depend on inconsistent, poor quality data. As an intermediate step to help current efforts by nonprofits to combat human trafficking, this project presents a model that is not dependent on quantitative data specific to human trafficking, but rather profiles the risk of human trafficking at the local level through causative factors. Businesses, indicated by the literature, were weighted based on the presence of characteristics that increase the likelihood of trafficking in persons. The mean risk was calculated by census tract to reveal the multiplicity of risk levels in both rural and urban settings. Results indicate that labor trafficking may be a more diffuse problem in Missouri than sex trafficking. Additionally, spatial patterns of risk remained largely the same regardless of adjustments made to the model.

  19. Acceptability of risk from radiation: Application to human space flight

    SciTech Connect

    1997-04-30

    This one of NASA`s sponsored activities of the NCRP. In 1983, NASA asked NCRP to examine radiation risks in space and to make recommendations about career radiation limits for astronauts (with cancer considered as the principal risk). In conjunction with that effort, NCRP was asked to convene this symposium; objective is to examine the technical, strategic, and philosophical issues pertaining to acceptable risk and radiation in space. Nine papers are included together with panel discussions and a summary. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  20. Human Research Program Human Health Countermeasures Element Nutrition Risk Standing Review Panel

    NASA Technical Reports Server (NTRS)

    Bistrian, Bruce

    2009-01-01

    The Nutrition Risk Standing Review Panel (SRP) reviewed and discussed the specific gaps and tasks for the Human Health Countermeasures (HHC) Element related to nutrition identified in the Human Research Program (HRP) Integrated Research Plan. There was general consensus that the described gaps and proposed tasks were critical to future NASA mission success. The SRP acknowledged the high scientific quality of the work currently being undertaken by the Nutritional Biochemistry group under the direction of Dr. Scott Smith. In review of the entire HRP, four new gaps were identified that complement the Element's existing research activities. Given the limitations of ground-based analogs for many of the unique physiological and metabolic alterations in space, future studies are needed to quantify nutritional factors that change during actual space flight. In addition, future tasks should seek to better evaluate the time course of physiological and metabolic alterations during flight to better predict alterations during longer duration missions. Finally, given the recent data suggesting a potential role for increased inflammatory responses during space flight, the role of inflammation needs to be explored in detail, including the development of potential countermeasures and new ground based analogs, if this possibility is confirmed.

  1. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis.

    PubMed

    Caini, Saverio; Boniol, Mathieu; Tosti, Giulio; Magi, Serena; Medri, Matelda; Stanganelli, Ignazio; Palli, Domenico; Assedi, Melania; Marmol, Veronique Del; Gandini, Sara

    2014-10-01

    Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.

  2. A comprehensive analysis of breast cancer news coverage in leading media outlets focusing on environmental risks and prevention.

    PubMed

    Atkin, Charles K; Smith, Sandi W; McFeters, Courtnay; Ferguson, Vanessa

    2008-01-01

    Breast cancer has a high profile in the news media, which are a major source of information for cancer patients and the general public. To determine the nature of breast cancer news coverage available to audiences, particularly on the topics of environmental risks and prevention, this content analysis measured a broad array of dimensions in 231 stories appearing in nine leading newspapers, newsmagazines, and television networks in 2003 and 2004. One fourth of all stories reported on various risks such as hormone replacement therapy (HRT) use. Very few items specifically addressed risks related to controllable lifestyle practices such as prepubertal obesity or chemical contaminants in the environment. About one third of the stories included prevention content, primarily focusing narrowly on use of pharmaceutical products. Little information described risk reduction via other individual preventive behaviors (e.g., diet, exercise, and smoking), parental protective measures, or collective actions to combat contamination sites. The more traditional categories of prevalence, detection, and treatment were featured in one third, one quarter, and two fifths of the news items, respectively. There were twice as many stories featuring personal narratives as statistical figures, and two thirds of all the news items cited expert medical professionals, researchers, or organizations. Implications of these findings and directions for future research are addressed.

  3. "My Baby & Me": Effects of an Early, Comprehensive Parenting Intervention on At-Risk Mothers and Their Children

    ERIC Educational Resources Information Center

    Guttentag, Cathy L.; Landry, Susan H.; Williams, Jeffrey M.; Baggett, Kathleen M.; Noria, Christine W.; Borkowski, John G.; Swank, Paul R.; Farris, Jaelyn R.; Crawford, April; Lanzi, Robin G.; Carta, Judith J.; Warren, Steven F.; Ramey, Sharon L.

    2014-01-01

    This study examined the efficacy of a multimodule parenting intervention, "My Baby & Me," that began prenatally and continued until children reached 2.5 years of age. The intervention targeted specific parenting skills designed to alter trajectories of maternal and child development. Of 361 high-risk mothers (193 adolescents, 168…

  4. About the Human Health Risk Assessment Research (HHRA) Program

    EPA Pesticide Factsheets

    The HHRA Research Program plays a unique role in serving the needs of the Agency, as well as the broader risk assessment/management community, by identifying, evaluating, synthesizing and integrating scientific information on chemical mixtures.

  5. A Comprehensive Approach to Risk Reduction for Asian and Pacific Islander American Women With HIV/AIDS.

    PubMed

    Sabato, Todd M

    2014-07-01

    As HIV incidence rises globally, Asian and Pacific Islander communities are increasingly affected. While often overlooked, Asian and Pacific Islander American women have shown the greatest percentage increase in HIV diagnosis rates. The development of a multilevel and multistrategy approach to HIV/AIDS education, prevention, and treatment among Asian and Pacific Islander females requires health care providers to identify personal and cultural barriers to prevention and treatment and implement culturally sensitive and specific measures. The purpose of this article is to illuminate barriers to HIV-related prevention, treatment, and care among Asian and Pacific Islander American females and provide practical application-based suggestions for providers, which may enhance Asian and Pacific Islander female inclusion in comprehensive HIV prevention.

  6. Use of mechanistic data in assessing human risks from exposure to particles.

    PubMed Central

    McClellan, R O

    1997-01-01

    The ultimate goal of toxicologic investigations of both natural and man-made fibrous and nonfibrous particles is to provide essential input for the assessment of potential human risks from exposure to these materials. The development of risk assessment procedures for airborne particles has evolved over the years. The earliest assessments for naturally occurring materials used direct human observations and incorporated safety factors to arrive at allowable human exposures. More recently, there has been a need to assess the potential risk associated with production and use of certain man-made materials for which human data are not available or are inadequate. For these materials, it has been necessary to assess human risks using data obtained from studies conducted in laboratory animals and with cells or tissues. During the last several decades, it has been suggested that data on the mechanisms by which particles cause disease could be used to reduce the uncertainty in estimates of human risks of particle exposures. This article provides comments on the use of mechanistic data in the risk assessment process and suggestions for increasing the successful development and use of mechanistic data in risk assessments conducted in the future. PMID:9400751

  7. Lobomycosis: Risk of Zoonotic Transmission from Dolphins to Humans

    PubMed Central

    Schaefer, Adam M.; Bossart, Gregory D.

    2013-01-01

    Abstract Lobomycosis, a fungal disease of the skin and subcutaneous tissues caused by Lacazia loboi, is sometimes referred to as a zoonotic disease because it affects only specific delphinidae and humans; however, the evidence that it can be transferred directly to humans from dolphins is weak. Dolphins have also been postulated to be responsible for an apparent geographic expansion of the disease in humans. Morphological and molecular differences between the human and dolphin organisms, differences in geographic distribution of the diseases between dolphins and humans, the existence of only a single documented case of presumed zoonotic transmission, and anecdotal evidence of lack of transmission to humans following accidental inoculation of tissue from infected dolphins do not support the hypothesis that dolphins infected with L. loboi represent a zoonotic hazard for humans. In addition, the lack of human cases in communities adjacent to coastal estuaries with a high prevalence of lobomycosis in dolphins, such as the Indian River Lagoon in Florida (IRL), suggests that direct or indirect transmission of L. loboi from dolphins to humans occurs rarely, if at all. Nonetheless, attention to personal hygiene and general principals of infection control are always appropriate when handling tissues from an animal with a presumptive diagnosis of a mycotic or fungal disease. PMID:23919604

  8. Lobomycosis: risk of zoonotic transmission from dolphins to humans.

    PubMed

    Reif, John S; Schaefer, Adam M; Bossart, Gregory D

    2013-10-01

    Lobomycosis, a fungal disease of the skin and subcutaneous tissues caused by Lacazia loboi, is sometimes referred to as a zoonotic disease because it affects only specific delphinidae and humans; however, the evidence that it can be transferred directly to humans from dolphins is weak. Dolphins have also been postulated to be responsible for an apparent geographic expansion of the disease in humans. Morphological and molecular differences between the human and dolphin organisms, differences in geographic distribution of the diseases between dolphins and humans, the existence of only a single documented case of presumed zoonotic transmission, and anecdotal evidence of lack of transmission to humans following accidental inoculation of tissue from infected dolphins do not support the hypothesis that dolphins infected with L. loboi represent a zoonotic hazard for humans. In addition, the lack of human cases in communities adjacent to coastal estuaries with a high prevalence of lobomycosis in dolphins, such as the Indian River Lagoon in Florida (IRL), suggests that direct or indirect transmission of L. loboi from dolphins to humans occurs rarely, if at all. Nonetheless, attention to personal hygiene and general principals of infection control are always appropriate when handling tissues from an animal with a presumptive diagnosis of a mycotic or fungal disease.

  9. Combining risk assessment and epidemiological risk factors to elucidate the sources of human E. coli O157 infection.

    PubMed

    Rotariu, O; Ogden, I D; MacRitchie, L; Forbes, K J; Williams, A P; Cross, P; Hunter, C J; Teunis, P F M; Strachan, N J C

    2012-08-01

    E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose-response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.

  10. Human health risk assessment related to contaminated land: state of the art.

    PubMed

    Swartjes, F A

    2015-08-01

    Exposure of humans to contaminants from contaminated land may result in many types of health damage ranging from relatively innocent symptoms such as skin eruption or nausea, on up to cancer or even death. Human health protection is generally considered as a major protection target. State-of-the-art possibilities and limitations of human health risk assessment tools are described in this paper. Human health risk assessment includes two different activities, i.e. the exposure assessment and the hazard assessment. The combination of these is called the risk characterization, which results in an appraisal of the contaminated land. Exposure assessment covers a smart combination of calculations, using exposure models, and measurements in contact media and body liquids and tissue (biomonitoring). Regarding the time frame represented by exposure estimates, biomonitoring generally relates to exposure history, measurements in contact media to actual exposures, while exposure calculations enable a focus on exposure in future situations. The hazard assessment, which is different for contaminants with or without a threshold for effects, results in a critical exposure value. Good human health risk assessment practice accounts for tiered approaches and multiple lines of evidence. Specific attention is given here to phenomena such as the time factor in human health risk assessment, suitability for the local situation, background exposure, combined exposure and harmonization of human health risk assessment tools.

  11. Preparation, Characterization, and Clinical Implications of Human Decellularized Adipose Tissue Extracellular Matrix (hDAM): A Comprehensive Review

    PubMed Central

    Banyard, Derek A.; Borad, Vedant; Amezcua, Eduardo; Wirth, Garrett A.; Evans, Gregory R.D.; Widgerow, Alan D.

    2016-01-01

    Fat grafting is commonly employed by plastic and reconstructive surgeons to address contour abnormalities and soft-tissue defects; however, because retention rates and thus volume filling effects are unpredictable, there is a search for new and innovative approaches. Initial studies on the use of human decellularized adipose tissue extracellular matrix (hDAM) show promise for its use not only in tissue engineering, but also in fat grafting. In this review, we examine and analyze the literature for the preparation, characterization, and use of hDAM and its derivatives in tissue engineering and plastic surgery applications. All studies reviewed involve physical, chemical, and/or biological treatment stages for the preparation of hDAM; however a distinction should be made between detergent and nondetergent-based processing, the latter of which appears to preserve the native integrity of the hDAM while most-efficiently achieving complete decellularization. Methods of hDAM characterization vary among groups and included simple and immunohistochemical staining, biochemical assays, 3-dimensional (3D) imaging, and mechano-stress testing, all of which are necessary to achieve a comprehensive description of this novel tissue. Finally, we examine the various preclinical models utilized to optimize hDAM performance, which primarily include the addition of adipose-derived stem cells or cross-linking agents. Overall, hDAM appears to be a promising adjunct in fat-grafting applications or even possibly as a stand-alone soft-tissue filler with off-the-shelf potential for commercial applications. PMID:26333991

  12. Waste area Grouping 2 Phase I task data report: Human health risk assessment

    SciTech Connect

    Purucker, S.T.; Douthat, D.M.

    1996-06-01

    This report is one of five reports issued in 1996 that provide follow- up information to the Phase 1 Remedial Investigation (RI) Report for Waste Area Grouping (WAG) 2 at Oak Ridge National Laboratory (ORNL). The five reports address areas of concern that could cause potential human health risk and ecological risk within WAG2 at ORNL. The purpose of this report is to present a summary of the human health risk assessment results based on the data collected for the WAG 2 Phase 1 RI. Estimates of risk are provided based on measured concentrations in the surface water, floodplain soil, and sediment of White Oak Creek, Melton Branch, and their tributaries. The human health risk assessment methodology used in this risk assessment is based on Risk Assessment Guidance for Superfund (RAGS). First, the data for the different media are elevated to determine usability for risk assessment. Second, through the process of selecting chemicals of potential concern (COPCs), contaminants to be considered in the risk assessment are identified for each assessment of exposure potential is performed, and exposure pathways are identified. Subsequently, exposure is estimated quantitatively, and the toxicity of each of the COPCs is determined. The results of these analyses are combined and summarized in a risk characterization.

  13. Enhancing Interdisciplinary Human System Risk Research Through Modeling and Network Approaches

    NASA Technical Reports Server (NTRS)

    Mindock, Jennifer; Lumpkins, Sarah; Shelhamer, Mark

    2015-01-01

    NASA's Human Research Program (HRP) supports research to reduce human health and performance risks inherent in future human space exploration missions. Understanding risk outcomes and contributing factors in an integrated manner allows HRP research to support development of efficient and effective mitigations from cross-disciplinary perspectives, and to enable resilient human and engineered systems for spaceflight. The purpose of this work is to support scientific collaborations and research portfolio management by utilizing modeling for analysis and visualization of current and potential future interdisciplinary efforts.

  14. Human Risk of Infection with Borrelia burgdorferi, the Lyme Disease Agent, in Eastern United States

    PubMed Central

    Diuk-Wasser, Maria A.; Hoen, Anne Gatewood; Cislo, Paul; Brinkerhoff, Robert; Hamer, Sarah A.; Rowland, Michelle; Cortinas, Roberto; Vourc'h, Gwenaël; Melton, Forrest; Hickling, Graham J.; Tsao, Jean I.; Bunikis, Jonas; Barbour, Alan G.; Kitron, Uriel; Piesman, Joseph; Fish, Durland

    2012-01-01

    The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection. PMID:22302869

  15. Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis

    PubMed Central

    Myte, Robin; Gylling, Björn; Häggström, Jenny; Schneede, Jörn; Magne Ueland, Per; Hallmans, Göran; Johansson, Ingegerd; Palmqvist, Richard; Van Guelpen, Bethany

    2017-01-01

    The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease. PMID:28233834

  16. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques

    PubMed Central

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-01-01

    Objective: Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. Data Sources: We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”. Study Selection: The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. Results: This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Conclusion: Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis. PMID:28303857

  17. The EPA's Human Exposure Research Program for Assessing Cumulative Risk in Communities

    EPA Science Inventory

    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...

  18. 75 FR 51815 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... (NTP); Center for the Evaluation of Risks to Human Reproduction (CERHR); Evaluation of the Health... reproduction and/or development and provide opinion on whether these substances are hazardous for...

  19. Human Health Risk Assessment Strategic Research Action Plan 2012-2016

    EPA Pesticide Factsheets

    This document outlines the strategic plan for EPA’s Human Health Risk Assessment research efforts, and how they support and are integrated into the overall research portfolio of the Agency’s Office of Research and Development.

  20. Cytogenetic monitoring of human populations at risk in Egypt: role of cytogenetic data in cancer risk assessment.

    PubMed Central

    Anwar, W A

    1991-01-01

    Somatic mutation plays a critical role in carcinogenesis. Numerous environmental agents can increase the probability that somatic mutation will occur. The use of genotoxicity testing is essential for assessing potential human toxicity so that hazards can be prevented. Cytogenetic monitoring of human populations exposed to chemicals has proved to be a useful tool for detecting the chemical mutagenic effects. Cytogenetic analyses of human chromosomes in peripheral lymphocytes allows direct detection of mutation in somatic cells. Different methods can be used for chromosomal analysis (conventional chromosomal analysis, sister chromatid exchange, micronucleus frequency detection). Micronucleus frequency can be detected either in peripheral blood lymphocytes or in exfoliated cells. Different examples of human population studies are presented. Several problems that are found in biomonitoring studies are discussed. These studies should help us learn about individual exposure assessment and biologically relevant doses, leading to quantitative assessment of human cancer risks. PMID:1820285

  1. EPA underestimates, oversimplifies, miscommunicates, and mismanages cancer risks by ignoring human susceptibility.

    PubMed

    Finkel, Adam M

    2014-10-01

    If exposed to an identical concentration of a carcinogen, every human being would face a different level of risk, determined by his or her genetic, environmental, medical, and other uniquely individual characteristics. Various lines of evidence indicate that this susceptibility variable is distributed rather broadly in the human population, with perhaps a factor of 25- to 50-fold between the center of this distribution and either of its tails, but cancer risk assessment at the EPA and elsewhere has always treated every (adult) human as identically susceptible. The National Academy of Sciences "Silver Book" concluded that EPA and the other agencies should fundamentally correct their mis-computation of carcinogenic risk in two ways: (1) adjust individual risk estimates upward to provide information about the upper tail; and (2) adjust population risk estimates upward (by about sevenfold) to correct an underestimation due to a mathematical property of the interindividual distribution of human susceptibility, in which the susceptibility averaged over the entire (right-skewed) population exceeds the median value for the typical human. In this issue of Risk Analysis, Kenneth Bogen disputes the second adjustment and endorses the first, though he also relegates the problem of underestimated individual risks to the realm of "equity concerns" that he says should have little if any bearing on risk management policy. In this article, I show why the basis for the population risk adjustment that the NAS recommended is correct-that current population cancer risk estimates, whether they are derived from animal bioassays or from human epidemiologic studies, likely provide estimates of the median with respect to human variation, which in turn must be an underestimate of the mean. If cancer risk estimates have larger "conservative" biases embedded in them, a premise I have disputed in many previous writings, such a defect would not excuse ignoring this additional bias in the

  2. Human Papillomavirus Vaccine as an Anticancer Vaccine: Collaborative Efforts to Promote Human Papillomavirus Vaccine in the National Comprehensive Cancer Control Program.

    PubMed

    Townsend, Julie S; Steele, C Brooke; Hayes, Nikki; Bhatt, Achal; Moore, Angela R

    2017-03-01

    Widespread use of the human papillomavirus (HPV) vaccine has the potential to reduce incidence from HPV-associated cancers. However, vaccine uptake among adolescents remains well below the Healthy People 2020 targets. The Centers for Disease Control and Prevention (CDC) National Comprehensive Cancer Control Program (NCCCP) awardees are well positioned to work with immunization programs to increase vaccine uptake. The CDC chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 to 2016 as part of program reporting requirements. A content analysis was conducted on the query results to categorize interventions according to strategies outlined in The Guide to Community Preventive Services and the 2014 President's Cancer Panel report. Sixty-two percent of NCCCP awardees had planned or implemented at least one activity since 2013 to address low HPV vaccination coverage in their jurisdictions. Most NCCCP awardees (86%) reported community education activities, while 65% reported activities associated with provider education. Systems-based strategies such as client reminders or provider assessment and feedback were each reported by less than 25% of NCCCP awardees. Many NCCCP awardees report planning or implementing activities to address low HPV vaccination coverage, often in conjunction with state immunization programs. NCCCP awardees can play a role in increasing HPV vaccination coverage through their cancer prevention and control expertise and access to partners in the healthcare community.

  3. Assessments of direct human exposure: the approach of EU risk assessments compared to scenario-based risk assessment.

    PubMed

    Wormuth, Matthias; Demou, Evangelia; Scheringer, Martin; Hungerbühler, Konrad

    2007-08-01

    The awareness of potential risks emerging from the use of chemicals in all parts of daily life has increased the need for risk assessments that are able to cover a high number of exposure situations and thereby ensure the safety of workers and consumers. In the European Union (EU), the practice of risk assessments for chemicals is laid down in a Technical Guidance Document; it is designed to consider environmental and human occupational and residential exposure. Almost 70 EU risk assessment reports (RARs) have been finalized for high-production-volume chemicals during the last decade. In the present study, we analyze the assessment of occupational and consumer exposure to trichloroethylene and phthalates presented in six EU RARs. Exposure scenarios in these six RARs were compared to scenarios used in applications of the scenario-based risk assessment approach to the same set of chemicals. We find that scenarios used in the selected EU RARs to represent typical exposure situations in occupational or private use of chemicals and products do not necessarily represent worst-case conditions. This can be due to the use of outdated information on technical equipment and conditions in workplaces or omission of pathways that can cause consumer exposure. Considering the need for exposure and risk assessments under the new chemicals legislation of the EU, we suggest that a transparent process of collecting data on exposure situations and of generating representative exposure scenarios is implemented to improve the accuracy of risk assessments. Also, the data sets used to assess human exposure should be harmonized, summarized in a transparent fashion, and made accessible for all risk assessors and the public.

  4. Impact of microbial count distributions on human health risk estimates.

    PubMed

    Duarte, A S R; Nauta, M J

    2015-02-16

    Quantitative microbiological risk assessment (QMRA) is influenced by the choice of the probability distribution used to describe pathogen concentrations, as this may eventually have a large effect on the distribution of doses at exposure. When fitting a probability distribution to microbial enumeration data, several factors may have an impact on the accuracy of that fit. Analysis of the best statistical fits of different distributions alone does not provide a clear indication of the impact in terms of risk estimates. Thus, in this study we focus on the impact of fitting microbial distributions on risk estimates, at two different concentration scenarios and at a range of prevalence levels. By using five different parametric distributions, we investigate whether different characteristics of a good fit are crucial for an accurate risk estimate. Among the factors studied are the importance of accounting for the Poisson randomness in counts, the difference between treating "true" zeroes as such or as censored below a limit of quantification (LOQ) and the importance of making the correct assumption about the underlying distribution of concentrations. By running a simulation experiment with zero-inflated Poisson-lognormal distributed data and an existing QMRA model from retail to consumer level, it was possible to assess the difference between expected risk and the risk estimated with using a lognormal, a zero-inflated lognormal, a Poisson-gamma, a zero-inflated Poisson-gamma and a zero-inflated Poisson-lognormal distribution. We show that the impact of the choice of different probability distributions to describe concentrations at retail on risk estimates is dependent both on concentration and prevalence levels. We also show that the use of an LOQ should be done consciously, especially when zero-inflation is not used. In general, zero-inflation does not necessarily improve the absolute risk estimation, but performance of zero-inflated distributions in QMRA tends to be

  5. NPP financial and regulatory risks-Importance of a balanced and comprehensive nuclear law for a newcomer country considering nuclear power programme

    NASA Astrophysics Data System (ADS)

    Manan, J. A. N. Abd; Mostafa, N. A.; Salim, M. F.

    2015-04-01

    The nature of Nuclear Power Plant (NPP) projects are: long duration (10-15 years for new build), high capital investment, reasonable risks and highly regulated industries to meet national & international requirement on Safety, Security, Safeguards (3S) and Liabilities. It requires long term planning and commitment from siting to final disposal of waste/spent fuel. Potential financial and regulatory risks are common in massive NPP projects and will be magnified in the case of using unproven technology. If the risks are not properly managed, it can lead to high project and operation costs, and, fail to fulfil its objectives to provide compatible electricity prices and. energy security. To ensure successful, the government and investors need to ensure that the NPP project is bankable with low cost of project and funding, have fair treatment and proper risk mitigation, and able to complete on time with no cost overrun. One of the requirements as prerequisite for the development of NPP as stipulated by the International Atomic Energy Agency (IAEA) is the establishment of a Legal and Regulatory Framework. The main objective of nuclear law is to ensure that the activities and projects carried-out in the country are legal and compliant to national and international requirements. The law should also be able to provide fair treatment of risks on its activities that is acceptable to investors. The challenge for a newcomer country is to develop a balanced and comprehensive national nuclear law that meet these objectives while taking into consideration various stakeholders' interest without compromising on safety, security, safeguard, liability requirements and other international obligations. This paper highlights the nature of NPP projects, its potential and associated financial and regulatory risks, and its major concerns and challenges. It proposes possible risks treatment and mitigation through the formulation of a balanced and comprehensive legislation by clear

  6. NPP financial and regulatory risks-Importance of a balanced and comprehensive nuclear law for a newcomer country considering nuclear power programme

    SciTech Connect

    Manan, J. A. N. Abd Mostafa, N. A.; Salim, M. F.

    2015-04-29

    The nature of Nuclear Power Plant (NPP) projects are: long duration (10-15 years for new build), high capital investment, reasonable risks and highly regulated industries to meet national and international requirement on Safety, Security, Safeguards (3S) and Liabilities. It requires long term planning and commitment from siting to final disposal of waste/spent fuel. Potential financial and regulatory risks are common in massive NPP projects and will be magnified in the case of using unproven technology. If the risks are not properly managed, it can lead to high project and operation costs, and, fail to fulfil its objectives to provide compatible electricity prices and. energy security. To ensure successful, the government and investors need to ensure that the NPP project is bankable with low cost of project and funding, have fair treatment and proper risk mitigation, and able to complete on time with no cost overrun. One of the requirements as prerequisite for the development of NPP as stipulated by the International Atomic Energy Agency (IAEA) is the establishment of a Legal and Regulatory Framework. The main objective of nuclear law is to ensure that the activities and projects carried-out in the country are legal and compliant to national and international requirements. The law should also be able to provide fair treatment of risks on its activities that is acceptable to investors. The challenge for a newcomer country is to develop a balanced and comprehensive national nuclear law that meet these objectives while taking into consideration various stakeholders’ interest without compromising on safety, security, safeguard, liability requirements and other international obligations. This paper highlights the nature of NPP projects, its potential and associated financial and regulatory risks, and its major concerns and challenges. It proposes possible risks treatment and mitigation through the formulation of a balanced and comprehensive legislation by clear

  7. Gastrointestinal and ectoparasites from urban stray dogs in Fortaleza (Brazil): high infection risk for humans?

    PubMed

    Klimpel, Sven; Heukelbach, Jörg; Pothmann, David; Rückert, Sonja

    2010-08-01

    Dogs are important definite or reservoir hosts for zoonotic parasites. However, only few studies on the prevalence of intestinal parasites in urban areas in Brazil are available. We performed a comprehensive study on parasites of stray dogs in a Brazilian metropolitan area. We included 46 stray dogs caught in the urban areas of Fortaleza (northeast Brazil). After euthanization, dogs were autopsied. Ectoparasites were collected, and the intestinal content of dogs were examined for the presence of parasites. Faecal samples were collected and analysed using merthiolate iodine formaldehyde concentration method. A total of nine different parasite species were found, including five endoparasite (one protozoan, one cestode and three nematode species) and four ectoparasite species (two flea, one louse and one tick species). In the intestinal content, 3,162 specimens of four helminth species were found: Ancylostoma caninum (prevalence, 95.7%), Dipylidium caninum (45.7%), Toxocara canis (8.7%) and Trichuris vulpis (4.3%). A total of 394 ectoparasite specimens were identified, including Rhipicephalus sanguineus (prevalence, 100.0%), Heterodoxus spiniger (67.4%), Ctenocephalides canis (39.1%) and Ctenocephalides felis (17.4%). In the faeces, intestinal parasites were detected in 38 stray dogs (82.6%), including oocysts of Giardia sp. (2.2%) and eggs of the nematode A. caninum (82.6%). Neither eggs nor larval stages of D. caninum, T. canis or T. vulpis were detected in dog faeces. Sensitivity of faecal examination for A. caninum was 86.4% (95% confidence interval, 72.0-94.3) but zero percentage for the other intestinal helminth species. Our data show that stray dogs in northeast Brazil carry a multitude of zoonotic ecto- and endoparasites, posing a considerable risk for humans. With the exception of A. caninum, sensitivity of faecal examination was negligible.

  8. Mentoring Programs to Affect Delinquency and Associated Outcomes of Youth At-Risk: A Comprehensive Meta-Analytic Reviewi

    PubMed Central

    Tolan, Patrick H.; Henry, David B.; Schoeny, Michael S.; Lovegrove, Peter; Nichols, Emily

    2013-01-01

    Objectives To conduct a meta-analytic review of selective and indicated mentoring interventions for effects for youth at risk on delinquency and key associated outcomes (aggression, drug use, academic functioning). We also undertook the first systematic evaluation of intervention implementation features and organization and tested for effects of theorized key processes of mentor program effects. Methods Campbell Collaboration review inclusion criteria and procedures were used to search and evaluate the literature. Criteria included a sample defined as at-risk for delinquency due to individual behavior such as aggression or conduct problems or environmental characteristics such as residence in high-crime community. Studies were required to be random assignment or strong quasi-experimental design. Of 163 identified studies published 1970 - 2011, 46 met criteria for inclusion. Results Mean effects sizes were significant and positive for each outcome category (ranging form d =.11 for Academic Achievement to d = .29 for Aggression). Heterogeneity in effect sizes was noted for all four outcomes. Stronger effects resulted when mentor motivation was professional development but not by other implementation features. Significant improvements in effects were found when advocacy and emotional support mentoring processes were emphasized. Conclusions This popular approach has significant impact on delinquency and associated outcomes for youth at-risk for delinquency. While evidencing some features may relate to effects, the body of literature is remarkably lacking in details about specific program features and procedures. This persistent state of limited reporting seriously impedes understanding about how mentoring is beneficial and ability to maximize its utility. PMID:25386111

  9. The risks of epidural and transforaminal steroid injections in the Spine: Commentary and a comprehensive review of the literature

    PubMed Central

    Epstein, Nancy E.

    2013-01-01

    Background: Multiple type of spinal injections, whether epidural/translaminar or transforaminal, facet injections, are offered to patients with/without surgical spinal lesions by pain management specialists (radiologists, physiatrists, and anesthesiologists). Although not approved by the Food and Drug Administration (FDA), injections are being performed with an increased frequency (160%), are typically short-acting and ineffective over the longer-term, while exposing patients to major risks/complications. Methods: For many patients with spinal pain alone and no surgical lesions, the “success” of epidural injections may simply reflect the self-limited course of the disease. Alternatively, although those with surgical pathology may experience transient or no pain relief, undergoing these injections (typically administered in a series of three) unnecessarily exposes them to the inherent risks, while also delaying surgery and potentially exposing them to more severe/permanent neurological deficits. Results: Multiple recent reports cite contaminated epidural steroid injections resulting in meningitis, stroke, paralysis, and death. The Center for Disease Control (CDC) specifically identified 25 deaths (many due to Aspergillosis), 337 patients sickened, and 14,000 exposed to contaminated steroids. Nevertheless, many other patients develop other complications that go unreported/underreported: Other life-threatening infections, spinal fluid leaks (0.4-6%), positional headaches (28%), adhesive arachnoiditis (6-16%), hydrocephalus, air embolism, urinary retention, allergic reactions, intravascular injections (7.9-11.6%), stroke, blindness, neurological deficits/paralysis, hematomas, seizures, and death. Conclusions: Although the benefits for epidural steroid injections may include transient pain relief for those with/without surgical disease, the multitude of risks attributed to these injections outweighs the benefits. PMID:23646278

  10. Astronaut Biography Project for Countermeasures of Human Behavior and Performance Risks in Long Duration Space Flights

    NASA Technical Reports Server (NTRS)

    Banks, Akeem

    2012-01-01

    This final report will summarize research that relates to human behavioral health and performance of astronauts and flight controllers. Literature reviews, data archival analyses, and ground-based analog studies that center around the risk of human space flight are being used to help mitigate human behavior and performance risks from long duration space flights. A qualitative analysis of an astronaut autobiography was completed. An analysis was also conducted on exercise countermeasure publications to show the positive affects of exercise on the risks targeted in this study. The three main risks targeted in this study are risks of behavioral and psychiatric disorders, risks of performance errors due to poor team performance, cohesion, and composition, and risks of performance errors due to sleep deprivation, circadian rhythm. These three risks focus on psychological and physiological aspects of astronauts who venture out into space on long duration space missions. The purpose of this research is to target these risks in order to help quantify, identify, and mature countermeasures and technologies required in preventing or mitigating adverse outcomes from exposure to the spaceflight environment

  11. The cyanobacteria toxins, microcystins – emerging risks to human health

    EPA Science Inventory

    Dialysis patients appear to be at increased risk for exposure to cyanobacteria toxins; episodes of microcystin (MCYST) exposure via dialysate during 1996 and 2001 have been previously reported. During 2001, as many as 44 renal insufficiency patients were exposed to contaminated d...

  12. Perception of Human-Derived Risk Influences Choice at Top of the Food Chain

    PubMed Central

    Cristescu, Bogdan; Stenhouse, Gordon B.; Boyce, Mark S.

    2013-01-01

    On human-used landscapes, animal behavior is a trade-off between maximizing fitness and minimizing human-derived risk. Understanding risk perception in wildlife can allow mitigation of anthropogenic risk, with benefits to long-term animal fitness. Areas where animals choose to rest should minimize risk from predators, which for large carnivores typically equate to humans. We hypothesize that high human activity leads to selection for habitat security, whereas low activity enables trading security for forage. We investigated selection of resting (bedding) sites by GPS radiocollared adult grizzly bears (n = 10) in a low density population on a multiple-use landscape in Canada. We compared security and foods at resting and random locations while accounting for land use, season, and time of day. On reclaimed mines with low human access, bears selected high horizontal cover far from trails, but did not avoid open (herbaceous) areas, resting primarily at night. In protected areas bears also bedded at night, in areas with berry shrubs and Hedysarum spp., with horizontal cover selected in the summer, during high human access. On public lands with substantial human recreation, bears bedded at day, selected resting sites with high horizontal cover in the summer and habitat edges, with bedding associated with herbaceous foods. These spatial and temporal patterns of selection suggest that bears perceive human-related risk differentially in relation to human activity level, season and time of day, and employ a security-food trade-off strategy. Although grizzly bears are presently not hunted in Alberta, their perceived risks associated with humans influence resting-site selection. PMID:24367549

  13. Perception of human-derived risk influences choice at top of the food chain.

    PubMed

    Cristescu, Bogdan; Stenhouse, Gordon B; Boyce, Mark S

    2013-01-01

    On human-used landscapes, animal behavior is a trade-off between maximizing fitness and minimizing human-derived risk. Understanding risk perception in wildlife can allow mitigation of anthropogenic risk, with benefits to long-term animal fitness. Areas where animals choose to rest should minimize risk from predators, which for large carnivores typically equate to humans. We hypothesize that high human activity leads to selection for habitat security, whereas low activity enables trading security for forage. We investigated selection of resting (bedding) sites by GPS radiocollared adult grizzly bears (n = 10) in a low density population on a multiple-use landscape in Canada. We compared security and foods at resting and random locations while accounting for land use, season, and time of day. On reclaimed mines with low human access, bears selected high horizontal cover far from trails, but did not avoid open (herbaceous) areas, resting primarily at night. In protected areas bears also bedded at night, in areas with berry shrubs and Hedysarum spp., with horizontal cover selected in the summer, during high human access. On public lands with substantial human recreation, bears bedded at day, selected resting sites with high horizontal cover in the summer and habitat edges, with bedding associated with herbaceous foods. These spatial and temporal patterns of selection suggest that bears perceive human-related risk differentially in relation to human activity level, season and time of day, and employ a security-food trade-off strategy. Although grizzly bears are presently not hunted in Alberta, their perceived risks associated with humans influence resting-site selection.

  14. An Updated Comprehensive Risk Analysis for Radioisotopes Identified of High Risk to National Security in the Event of a Radiological Dispersion Device Scenario

    NASA Astrophysics Data System (ADS)

    Robinson, Alexandra R.

    An updated global survey of radioisotope production and distribution was completed and subjected to a revised "down-selection methodology" to determine those radioisotopes that should be classified as potential national security risks based on availability and key physical characteristics that could be exploited in a hypothetical radiological dispersion device. The potential at-risk radioisotopes then were used in a modeling software suite known as Turbo FRMAC, developed by Sandia National Laboratories, to characterize plausible contamination maps known as Protective Action Guideline Zone Maps. This software also was used to calculate the whole body dose equivalent for exposed individuals based on various dispersion parameters and scenarios. Derived Response Levels then were determined for each radioisotope using: 1) target doses to members of the public provided by the U.S. EPA, and 2) occupational dose limits provided by the U.S. Nuclear Regulatory Commission. The limiting Derived Response Level for each radioisotope also was determined.

  15. A global human health risk assessment for Decamethylcyclopentasiloxane (D5).

    PubMed

    Franzen, Allison; Van Landingham, Cynthia; Greene, Tracy; Plotzke, Kathy; Gentry, Robinan

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a low-molecular-weight cyclic siloxane used primarily as an intermediate in the production of several widely-used industrial and consumer products and intentionally added to consumer products, personal products and some dry cleaning solvents. The global use requires consideration of consumer use information and risk assessment requirements from various sources and authoritative bodies. A global "harmonized" risk assessment was conducted to meet requirements for substance-specific risk assessments conducted by regulatory agencies such as USEPA's Integrated Risk Information System (IRIS), Health Canada and various independent scientific committees of the European Commission, as well as provide guidance for chemical safety assessments under REACH in Europe, and other relevant authoritative bodies. This risk assessment incorporates global exposure information combined with a Monte Carlo analysis to determine the most significant routes of exposure, utilization of a multi-species, multi-route physiologically based pharmacokinetic (PBPK) model to estimate internal dose metrics, benchmark modeling to determine a point of departure (POD), and a margin of safety (MOS) evaluation to compare the estimates of intake with the POD. Because of the specific pharmacokinetic behaviors of D5 including high lipophilicity, high volatility with low blood-to-air partition coefficients and extensive metabolic clearance that regulate tissue dose after exposure, the use of a PBPK model was essential to provide a comparison of a dose metric that reflects these processes. The characterization of the potential for adverse effects after exposure to D5 using a MOS approach based on an internal dose metric removes the subjective application of uncertainty factors that may be applied across various regulatory agencies and allows examination of the differences between internal dose metrics associated with exposure and those associated with adverse effects.

  16. Human KZNF Gene Catalog - A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors

    DOE Data Explorer

    Huntley, S; Baggott, D. M.; Hamilton, A. T.; Tran-Gyamfi, M.; Yang, S.; Kim, J.; Gordon, L.; Branscomb, E.; Stubbs, L.

    Kruppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets. [This abstract was copied from: S Huntley, DM Baggott, AT Hamilton, M Tran-Gyamfi, S Yang, J Kim, L Gordon, E Branscomb, and L Stubbs. 2006. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors, Genome Research 16(5):669 - 677] The website provides the

  17. Effect of comprehensive cardiovascular disease risk management on longitudinal changes in carotid artery intima-media thickness in a community-based prevention clinic

    PubMed Central

    Cheng, Henry G.; Patel, Birju S.; Martin, Seth S.; Blaha, Michael; Doneen, Amy; Bale, Brad

    2016-01-01

    Introduction The aim of the study was to examine changes in carotid intima-media thickness (CIMT) and carotid plaque morphology in patients receiving multifactorial cardiovascular disease (CVD) risk factor management in a community-based prevention clinic. Quantitative changes in CIMT and qualitative changes in carotid plaque morphology may be measured non-invasively by ultrasound. Material and methods This is a retrospective study on a cohort of 324 patients who received multifactorial cardiovascular risk reduction treatment at a community prevention clinic. All patients received lipid-lowering medications (statin, niacin, and/or ezetimibe) and lifestyle modification. All patients underwent at least one follow-up CIMT measurement after starting their regimen. Annual biomarker, CIMT, and plaque measurements were analyzed for associations with CVD risk reduction treatment. Results Median time to last CIMT was 3.0 years. Compared to baseline, follow-up analysis of all treatment groups at 2 years showed a 52.7% decrease in max CIMT, a 3.0% decrease in mean CIMT, and an 87.0% decrease in the difference between max and mean CIMT (p < 0.001). Plaque composition changes occurred, including a decrease in lipid-rich plaques of 78.4% within the first 2 years (p < 0.001). After the first 2 years, CIMT and lipid-rich plaques continued to decline at reduced rates. Conclusion In a cohort of patients receiving comprehensive CVD risk reduction therapy, delipidation of subclinical carotid plaque and reductions in CIMT predominantly occurred within 2 years, and correlated with changes in traditional biomarkers. These observations, generated from existing clinical data, provide unique insight into the longitudinal on-treatment changes in carotid plaque. PMID:27478452

  18. BIOTOXIN-INDUCED NEUROTOXICITY: AN EMERGING RISK FOR HUMAN HEALTH AND ECOLOGY.

    EPA Science Inventory

    The increasing incidence of human illness associated with exposure to biotoxins from harmful algal blooms (HABs) in aquatic environments, and fungi and bacteria on land, may indicate an emerging human-health risk. HABs are reported to be increasing worldwide in frequency, duratio...

  19. Biomarkers of benzene exposure and their interpretation for human health risk assessment

    EPA Science Inventory

    Human biomarkers of exposure such as parent or metabolite concentrations in blood or urine are often reported without any context to the sources of exposure or the implications for human risk. The Biomonitoring Technical Committee of the International Life Sciences Institute/Huma...

  20. 75 FR 2545 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction (CERHR); Availability of the Final Expert Panel Report on...

  1. Human health risks in megacities due to air pollution

    NASA Astrophysics Data System (ADS)

    Gurjar, B. R.; Jain, A.; Sharma, A.; Agarwal, A.; Gupta, P.; Nagpure, A. S.; Lelieveld, J.

    2010-11-01

    This study evaluates the health risks in megacities in terms of mortality and morbidity due to air pollution. A new spreadsheet model, Risk of Mortality/Morbidity due to Air Pollution (Ri-MAP), is used to estimate the excess numbers of deaths and illnesses. By adopting the World Health Organization (WHO) guideline concentrations for the air pollutants SO 2, NO 2 and total suspended particles (TSP), concentration-response relationships and a population attributable-risk proportion concept are employed. Results suggest that some megacities like Los Angeles, New York, Osaka Kobe, Sao Paulo and Tokyo have very low excess cases in total mortality from these pollutants. In contrast, the approximate numbers of cases is highest in Karachi (15,000/yr) characterized by a very high concentration of total TSP (˜670 μg m -3). Dhaka (7000/yr), Beijing (5500/yr), Karachi (5200/yr), Cairo (5000/yr) and Delhi (3500/yr) rank highest with cardiovascular mortality. The morbidity (hospital admissions) due to Chronic Obstructive Pulmonary Disease (COPD) follows the tendency of cardiovascular mortality. Dhaka and Karachi lead the rankings, having about 2100/yr excess cases, while Osaka-Kobe (˜20/yr) and Sao Paulo (˜50/yr) are at the low end of all megacities considered. Since air pollution is increasing in many megacities, and our database of measured pollutants is limited to the period up to 2000 and does not include all relevant components (e.g. O 3), these numbers should be interpreted as lower limits. South Asian megacities most urgently need improvement of air quality to prevent excess mortality and morbidity due to exceptionally high levels of air pollution. The risk estimates obtained from Ri-MAP present a realistic baseline evaluation for the consequences of ambient air pollution in comparison to simple air quality indices, and can be expanded and improved in parallel with the development of air pollution monitoring networks.

  2. Framework for integrating human and animal data in chemical risk assessment.

    PubMed

    Lavelle, Karlene S; Robert Schnatter, A; Travis, Kim Z; Swaen, Gerard M H; Pallapies, Dirk; Money, Chris; Priem, Peter; Vrijhof, Henk

    2012-03-01

    Although regulatory agencies formally encourage the integration of all available data in chemical risk assessment, consistent implementation of this practice has been constrained by the lack of a clear, systematic method for doing so. In this paper, we describe a methodology for evaluating, classifying and integrating human and animal data into the risk assessment process that incorporates: (1) a balanced appraisal of human and animal data, (2) relevance to different stages of the risk assessment process, and (3) accommodation for different data quality requirements. The proposed framework offers a flexible, step-wise approach for determining which set of available data best support the chemical risk assessment that involves the rating and relative ranking of human and animal data quality. The evaluation of human data incorporates seven data quality elements, nature and specificity of the lead effect; evaluation of animal data incorporates data quality and relevance to humans. Results of simulations with selected chemicals previously evaluated in a formal risk assessment generally agreed with existing regulatory guidance. Application of the proposed framework across a wider range of chemical agents will improve transparency of the risk assessment process and validity of results, while informing continuous refinements to this evolving methodology.

  3. Comprehensive Environmental Assessment Applied to ...

    EPA Pesticide Factsheets

    In September 2013, EPA announced the availability of the final report, Comprehensive Environmental Assessment Applied to Multiwalled Carbon Nanotube Flame-Retardant Coatings in Upholstery Textiles: A Case Study Presenting Priority Research Gaps for Future Risk Assessments. This final report presents a case study of multiwalled carbon nanotubes (MWCNTs); it focuses on the specific example of MWCNTs as used in flame-retardant coatings applied to upholstery textiles. This case study is organized around the comprehensive environmental assessment (CEA) framework, which structures available information pertaining to the product life cycle, environmental transport and fate, exposure-dose in receptors (i.e., humans, ecological populations, and the environment), and potential impacts in these receptors. A group of experts representing multiple disciplines and multiple sector perspectives used an earlier draft of the case study in conjunction with a structured workshop process to identify and prioritize research gaps that, if pursued, could inform future MWCNT assessment efforts. The final report is not a health, risk, or exposure assessment and as such does not draw conclusions about potential risks, or present an exhaustive review of the literature. Rather, it presents the MWCNT research priorities that experts identified in this application of CEA in order to aid research planning throughout the scientific community. The outcomes of these research efforts may subsequ

  4. Human Perceptions Mirror Realities of Carnivore Attack Risk for Livestock: Implications for Mitigating Human-Carnivore Conflict

    PubMed Central

    Miller, Jennifer R. B.; Jhala, Yadvendradev V.; Schmitz, Oswald J.

    2016-01-01

    Human-carnivore conflict is challenging to quantify because it is shaped by both the realities and people’s perceptions of carnivore threats. Whether perceptions align with realities can have implications for conflict mitigation: misalignments can lead to heightened and indiscriminant persecution of carnivores whereas alignments can offer deeper insights into human-carnivore interactions. We applied a landscape-scale spatial analysis of livestock killed by tigers and leopards in India to model and map observed attack risk, and surveyed owners of livestock killed by tigers and leopards for their rankings of threats across habitats to map perceived attack risk. Observed tiger risk to livestock was greatest near dense forests and at moderate distances from human activity while leopard risk was greatest near open vegetation. People accurately perceived spatial differences between tiger and leopard hunting patterns, expected greater threat in areas with high values of observed risk for both carnivores. Owners’ perception of threats largely did not depend on environmental conditions surrounding their village (spatial location, dominant land-use or observed carnivore risk). Surveys revealed that owners who previously lost livestock to carnivores used more livestock protection methods than those who had no prior losses, and that owners who had recently lost livestock for the first time expressed greater interest in changing their protection methods than those who experienced prior losses. Our findings suggest that in systems where realities and perceptions of carnivore risk align, conservation programs and policies can optimize conservation outcomes by (1) improving the effectiveness of livestock protection methods and (2) working with owners who have recently lost livestock and are most willing to invest effort in adapting protection strategies to mitigate human-carnivore conflict. PMID:27617831

  5. Anticipating risk for human subjects participating in clinical research: application of Failure Mode and Effects Analysis.

    PubMed

    Cody, Robert J

    2006-03-01

    Failure Mode and Effects Analysis (FMEA) is a method applied in various industries to anticipate and mitigate risk. This methodology can be more systematically applied to the protection of human subjects in research. The purpose of FMEA is simple: prevent problems before they occur. By applying FMEA process analysis to the elements of a specific research protocol, the failure severity, occurrence, and detection rates can be estimated for calculation of a "risk priority number" (RPN). Methods can then be identified to reduce the RPN to levels where the risk/benefit ratio favors human subject benefit, to a greater magnitude than existed in the pre-analysis risk profile. At the very least, the approach provides a checklist of issues that can be individualized for specific research protocols or human subject populations.

  6. Prevalence of and Associated Risk Factors for High Risk Human Papillomavirus among Sexually Active Women, Swaziland

    PubMed Central

    Dlamini, Xolisile; Almonte, Maribel; Herrero, Rolando; Jolly, Pauline E.; Tsoka-Gwegweni, Joyce M.; Weiderpass, Elisabete; Broutet, Nathalie; Sartorius, Benn

    2017-01-01

    Background High risk human papillomavirus (hr-HPV) infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs) such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland. Methods A total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays. Results The overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8–49.5). Of hr-HPV infected women, 12.4% (95%CI: 8.6–17.5) were HPV16-positive, 13.8% (95%CI:12.0–15.8) were positive for HPV18/45, 26.7% (95%CI: 24.2–29.3) for HPV31/33/35/52/58, 7.6% (95%CI: 7.6–11.9) for HPV51/59 and 11.0%, (95%CI: 7.9–15.3) for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7–46.2). HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043–7.8, p<0.001). Overall hr-HPV/HIV co-infection was 24.4% (95%CI: 20.3–29.1) which was significantly higher among younger age groups (p<0.001). Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus -negative women (27.7% and 12.7% respectively, p<0.001). The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6–7.1, OR = 4.6, 95%CI: 2.8–7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3–13.4, p<0.021 respectively). Conclusion The prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention

  7. Comprehensive assessment of the association between DNA repair gene XRCC3 rs861539 C/T polymorphism and lung cancer risk.

    PubMed

    Ding, Gang; Xu, Weiguo; Hua, Hongwei; Huang, Qian; Liang, Hongxiang; Ni, Yufeng; Ding, Zhaoheng

    2013-10-01

    A few case-control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case-control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89-1.13), P = 0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81-1.41), P = 0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84-1.07), P = 0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86-1.39), P = 0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.

  8. LastQuake: a comprehensive strategy for rapid engagement of earthquake eyewitnesses, massive crowdsourcing and risk reduction

    NASA Astrophysics Data System (ADS)

    Bossu, R.; Roussel, F.; Mazet-Roux, G.; Steed, R.; Frobert, L.

    2015-12-01

    LastQuake is a smartphone app, browser add-on and the most sophisticated Twitter robot (quakebot) for earthquakes currently in operation. It fulfills eyewitnesses' needs by offering information on felt earthquakes and their effects within tens of seconds of their occurrence. Associated with an active presence on Facebook, Pinterest and on websites, this proves a very efficient engagement strategy. For example, the app was installed thousands of times after the Ghorka earthquake in Nepal. Language barriers have been erased by using visual communication; for example, felt reports are collected through a set of cartoons representing different shaking levels. Within 3 weeks of the magnitude 7.8 Ghorka earthquakes, 7,000 felt reports with thousands of comments were collected related to the mainshock and tens of its aftershocks as well as 100 informative geo-located pics. The QuakeBot was essential in allowing us to be identified so well and interact with those affected. LastQuake is also a risk reduction tool since it provides rapid information. Rapid information is similar to prevention since when it does not exist, disasters can happen. When no information is available after a felt earthquake, the public block emergency lines by trying to find out the cause of the shaking, crowds form potentially leading to unpredictable crowd movement, rumors spread. In its next release LastQuake will also provide people with guidance immediately after a shaking through a number of pop-up cartoons illustrating "do/don't do" items (go to open places, do not phone emergency services except if people are injured…). LastQuake's app design is simple and intuitive and has a global audience. It benefited from a crowdfunding campaign (and the support of the Fondation MAIF) and more improvements have been planned after an online feedback campaign organized in early June with the Ghorka earthquake eyewitnesses. LastQuake is also a seismic risk reduction tools thanks to its very rapid

  9. "My Baby & Me": effects of an early, comprehensive parenting intervention on at-risk mothers and their children.

    PubMed

    Guttentag, Cathy L; Landry, Susan H; Williams, Jeffrey M; Baggett, Kathleen M; Noria, Christine W; Borkowski, John G; Swank, Paul R; Farris, Jaelyn R; Crawford, April; Lanzi, Robin G; Carta, Judith J; Warren, Steven F; Ramey, Sharon L

    2014-05-01

    This study examined the efficacy of a multimodule parenting intervention, "My Baby & Me," that began prenatally and continued until children reached 2.5 years of age. The intervention targeted specific parenting skills designed to alter trajectories of maternal and child development. Of 361 high-risk mothers (193 adolescents, 168 adults) enrolled across 4 states, half were randomly assigned to the high-intensity (HI) home visitation coaching program (55 sessions), and half to a low-intensity (LI) condition that included monthly phone calls from a coach, printed informational materials, and community resource referrals. Videotaped observations of mother-child play were coded at 5 time points for multiple maternal and child behaviors and skills. Compared to mothers in the LI group, mothers in the HI group showed higher levels of contingent responsiveness, higher quality verbal stimulation, and more verbal scaffolding by 30 months, with higher levels of warmth and greater decreases in physical intrusiveness and negativity when their children were 24 months. By 30 months, children in the HI group showed more rapid increases and higher levels of engagement with the environment, expressive language skills, and social engagement, as well as more complex toy play and fewer problem behaviors than those in the LI group. Gains in maternal responsive behaviors mediated the effects of the intervention on child outcomes. Results were comparable for adolescent and adult mothers. A strong theoretical framework, consistent focus on maternal responsiveness, high dosage, and trusting relationships with coaches are thought to explain the positive outcomes.

  10. Toxic phytochemicals and their potential risks for human cancer

    PubMed Central

    Bode, Ann M.; Dong, Zigang

    2014-01-01

    Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided. PMID:25348854

  11. Human immunoglobulin G levels of viruses and associated glioma risk.

    PubMed

    Sjöström, Sara; Hjalmars, Ulf; Juto, Per; Wadell, Göran; Hallmans, Göran; Tjönneland, Anne; Halkjaer, Jytte; Manjer, Jonas; Almquist, Martin; Melin, Beatrice S

    2011-09-01

    Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.

  12. Human health risk characterization of petroleum coke calcining facility emissions.

    PubMed

    Singh, Davinderjit; Johnson, Giffe T; Harbison, Raymond D

    2015-12-01

    Calcining processes including handling and storage of raw petroleum coke may result in Particulate Matter (PM) and gaseous emissions. Concerns have been raised over the potential association between particulate and aerosol pollution and adverse respiratory health effects including decrements in lung function. This risk characterization evaluated the exposure concentrations of ambient air pollutants including PM1