Science.gov

Sample records for comprehensive human risk

  1. 12 CFR 217.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Comprehensive risk. 217.209 Section 217.209... ADEQUACY OF BOARD-REGULATED INSTITUTIONS Risk-Weighted Assets-Market Risk § 217.209 Comprehensive risk. (a... the method in this section to measure comprehensive risk, that is, all price risk, for one or...

  2. 12 CFR 324.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Comprehensive risk. 324.209 Section 324.209... CAPITAL ADEQUACY OF FDIC-SUPERVISED INSTITUTIONS Risk-Weighted Assets-Market Risk § 324.209 Comprehensive risk. (a) General requirement. (1) Subject to the prior approval of the FDIC, an...

  3. 12 CFR 3.209 - Comprehensive risk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Comprehensive risk. 3.209 Section 3.209 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY CAPITAL ADEQUACY STANDARDS Risk-Weighted Assets-Market Risk § 3.209 Comprehensive risk. (a) General requirement. (1) Subject to the...

  4. 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.

  5. 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.

  6. Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.

    PubMed

    Clements, Mike; Millar, Val; Williams, Angela S; Kalinka, Sian

    2015-11-01

    More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form of functional assays to predict the potential for drug-induced ECG abnormalities in vivo. Cardiotoxicity can also be structural in nature, so a full and efficient assessment of cardiac liabilities for new chemical entities should account for both these phenomena. As well as providing a more appropriate nonclinical model for in vitro cardiotoxicity testing, human stem cell-derived cardiomyocytes offer an integrated system to study drug impact on cardiomyocyte structure as well as function. Employing human embryonic stem cell-derived cardiacmyocytes (hESC-CMs) on 3 assay platforms with complementary insights into cardiac biology (multielectrode array assay, electrophysiology; impedance assay, cell movement/beating; and high content analysis assay, subcellular structure) we profiled a panel of 13 drugs with well characterized cardiac liabilities (Amiodarone, Aspirin, Astemizole, Axitinib, AZT, Bepridil, Doxorubicin, E-4031, Mexiletine, Rosiglitazone, Sunitinib, Sibutramine, and Verapamil). Our data show good correlations with previous studies and reported clinical observations. Using multiparameter phenotypic profiling techniques we demonstrate the dynamic relationship that exists between functional and structural toxicity, and the benefits of this more holistic approach to risk assessment. We conclude by showing for the first time how the advent of transparent MEA plate technology enables functional and structural cardiotoxic responses to be recorded from the same cell population. This approach more directly links changes in morphology of the hESC-CMs with recorded electrophysiology signatures, offering even greater insight into the wide range of potential drug impacts on cardiac physiology, with a throughput that is more amenable to early drug discovery. PMID:26259608

  7. 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

  8. 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

  9. 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

  10. 76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability... availability of EPA's preliminary human health risk assessment for the registration review of chlorpyrifos and... comprehensive preliminary human health risk assessment for all chlorpyrifos uses. After reviewing...

  11. 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

  12. 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.

  13. 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. PMID:26212387

  14. 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

  15. 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.

  16. 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

  17. Risks and complications of coronary angiography: a comprehensive review.

    PubMed

    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

  18. Comprehensive schoolteachers at risk of early exit from work.

    PubMed

    Mykletun, R J; Mykletun, A

    1999-01-01

    Risk of early exit from work for teachers was operationalized as high burnout scores, working part-time due to heavy burden and illness or working part-time while also receiving partial disability pension. Data were collected by mailed questionnaires in a cross-sectional study to a random sample of Norwegian comprehensive schoolteachers, response rate = 86% (N = 1860 valid cases). High age increased the risk of early exit from work, but for cynicism the age effect disappeared when sense of competence and stress were introduced in the regression model. Age had no effect for low professional efficacy. Sense of competence effected burnout, but actual competence level and the gap between actual competence and teaching obligations did not. Stress effected all measures of risk of early exit, especially exhaustion. Change as stress factor increased the exhaustion scores, and were also relevant to risk of having a part-time position, and/or partial disability pension. PMID:10553518

  19. 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

  20. Comprehensive variation discovery in single human genomes

    PubMed Central

    Weisenfeld, Neil I.; Yin, Shuangye; Sharpe, Ted; Lau, Bayo; Hegarty, Ryan; Holmes, Laurie; Sogoloff, Brian; Tabbaa, Diana; Williams, Louise; Russ, Carsten; Nusbaum, Chad; Lander, Eric S.; MacCallum, Iain; Jaffe, David B.

    2014-01-01

    Complete knowledge of the genetic variation in individual human genomes is a crucial foundation for understanding the etiology of disease. Genetic variation is typically characterized by sequencing individual genomes and comparing reads to a reference. Existing methods do an excellent job of detecting variants in approximately 90% of the human genome, however calling variants in the remaining 10% of the genome (largely low-complexity sequence and segmental duplications) is challenging. To improve variant calling, we developed a new algorithm, DISCOVAR, and examined its performance on improved, low-cost sequence data. Using a newly created reference set of variants from finished sequence of 103 randomly chosen Fosmids, we find that some standard variant call sets miss up to 25% of variants. We show that the combination of new methods and improved data increases sensitivity several-fold, with the greatest impact in challenging regions of the human genome. PMID:25326702

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  3. 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…

  4. A Comprehensive Approach to the Humanities.

    ERIC Educational Resources Information Center

    Milner, Joseph O.; Milner, Lucy M.

    1986-01-01

    Describes the humanities curriculum at the North Carolina Governor's School which focuses on two courses of study: (1) one of ten academic disciplines (art, choral music, dance, drama , English, foreign language, instrumental music, math, natural science, social science), and (2) foundations in epistemology. (SRT)

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

    EPA Science Inventory

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

  6. 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.

  7. Comprehensive Proteomic Analysis of Human Erythropoiesis.

    PubMed

    Gautier, Emilie-Fleur; Ducamp, Sarah; Leduc, Marjorie; Salnot, Virginie; Guillonneau, François; Dussiot, Michael; Hale, John; Giarratana, Marie-Catherine; Raimbault, Anna; Douay, Luc; Lacombe, Catherine; Mohandas, Narla; Verdier, Frédérique; Zermati, Yael; Mayeux, Patrick

    2016-08-01

    Mass spectrometry-based proteomics now enables the absolute quantification of thousands of proteins in individual cell types. We used this technology to analyze the dynamic proteome changes occurring during human erythropoiesis. We quantified the absolute expression of 6,130 proteins during erythroid differentiation from late burst-forming units-erythroid (BFU-Es) to orthochromatic erythroblasts. A modest correlation between mRNA and protein expression was observed. We identified several proteins with unexpected expression patterns in erythroid cells, highlighting a breakpoint in the erythroid differentiation process at the basophilic stage. We also quantified the distribution of proteins between reticulocytes and pyrenocytes after enucleation. These analyses identified proteins that are actively sorted either with the reticulocyte or the pyrenocyte. Our study provides the absolute quantification of protein expression during a complex cellular differentiation process in humans, and it establishes a framework for future studies of disordered erythropoiesis. PMID:27452463

  8. 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.

  9. 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.

  10. 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

  11. 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. PMID:24293267

  12. 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…

  13. A Comprehensive Map of the Human Urinary Proteome

    PubMed Central

    Marimuthu, Arivusudar; O’Meally, Robert N.; Chaerkady, Raghothama; Subbannayya, Yashwanth; Nanjappa, Vishalakshi; Kumar, Praveen; Kelkar, Dhanashree S.; Pinto, Sneha M.; Sharma, Rakesh; Renuse, Santosh; Goel, Renu; Christopher, Rita; Delanghe, Bernard; Cole, Robert N.; Harsha, H.C.; Pandey, Akhilesh

    2014-01-01

    The study of the human urinary proteome has the potential to offer significant insights into normal physiology as well as disease pathology. The information obtained from such studies could be applied to the diagnosis of various diseases. The high sensitivity, resolution, and mass accuracy of the latest generation of mass spectrometers provides an opportunity to accurately catalog the proteins present in human urine, including those present at low levels. To this end, we carried out a comprehensive analysis of human urinary proteome from healthy individuals using high-resolution Fourier transform mass spectrometry. Importantly, we used the Orbitrap for detecting ions in both MS (resolution 60 000) and MS/MS (resolution 15 000) modes. To increase the depth of our analysis, we characterized both unfractionated as well as lectin-enriched proteins in our experiments. In all, we identified 1823 proteins with less than 1% false discovery rate, of which 671 proteins have not previously been reported as constituents of human urine. This data set should serve as a comprehensive reference list for future studies aimed at identification and characterization of urinary biomarkers for various diseases. PMID:21500864

  14. 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. PMID:27493014

  15. Human factors and risk assessment

    SciTech Connect

    Al-Minhali, A.

    1996-11-01

    A case study was presented in the 1994 Abu Dhabi International Exhibition and Conference (ADIPEC, 94) which discussed the importance of investigating human factors in the design of a high integrity protection system (HIPS) to be installed on an offshore high pressure gas platform, (SPE reference ADSPE 80). This paper will follow up on the design changes, installation and operation of the HIPS with emphasis on practical implications as a result of improper integration of human factors in the system reliability and risk assessment studies.

  16. A comprehensive catalogue and classification of human thermal climate indices

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    The very large number of human thermal climate indices that have been proposed over the past 100 years or so is a manifestation of the perceived importance within the scientific community of the thermal environment and the desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, the relative sophistication of the underlying body-atmosphere heat exchange theory and the particular design for application. They also vary considerably in type and quality, as well as in several other aspects. Reviews appear in the literature, but they cover a limited number of indices. A project that produces a comprehensive documentation, classification and overall evaluation of the full range of existing human thermal climate indices has never been attempted. This paper deals with documentation and classification. A subsequent report will focus on evaluation. Here a comprehensive register of 162 thermal indices is assembled and a sorting scheme devised that groups them according to eight primary classification classes. It is the first stage in a project to organise and evaluate the full range of all human thermal climate indices. The work, when completed, will make it easier for users to reflect on the merits of all available thermal indices. It will be simpler to locate and compare indices and decide which is most appropriate for a particular application or investigation.

  17. 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

  18. Comprehensive identification and analysis of human accelerated regulatory DNA.

    PubMed

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

    2015-09-01

    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. PMID:26448391

  20. Comprehensive genetic counseling for families at risk for HNPCC: impact on distress and perceptions.

    PubMed

    Keller, M; Jost, R; Haunstetter, C Mastromarino; Kienle, P; Knaebel, H P; Gebert, J; Sutter, C; Knebel-Doeberitz, M v; Cremer, F; Mazitschek, U

    2002-01-01

    The aim of the study was to explore distress and health beliefs before and after comprehensive interdisciplinary counseling in families at risk for hereditary non-polyposis colorectal cancer (HNPCC). Results reported here were derived from a consecutive sample of 65 counselees [31 patients with colorectal cancer (CRC) and 34 unaffected at-risk persons] who participated in interdisciplinary counseling provided by human geneticists, surgeons, and psycho-oncologists before genetic testing. Data were collected from self-administered questionnaires before, as well as 4-6 weeks after, counseling. Distress and perceptions specific to HNPCC were assessed at both timepoints using standardized as well as author-derived instruments. Distress declined after counseling, as did worries related to HNPCC. An increase was found in personal belief in control of cancer risk, for instance, in the perceived efficacy of early detection of CRC. We also observed a trend toward greater anticipated ability to cope with a positive gene test after counseling. Changes after counseling were generally more pronounced for persons at risk, as compared to patients with cancer. The decrease in distress was partly attributable to an increase in personal self-confidence. One-third of the sample reported enhanced communication specific to hereditary disease within the family after counseling. A substantial minority, however, said they experienced increased worry and physical symptoms after counseling. Overall, counselees demonstrated less stress and perceived cancer threat as well as enhanced beliefs regarding personal control over cancer, suggesting an overall beneficial impact of comprehensive counseling. Further research is needed to identify those individuals most at risk for increased fear and worry related to HNPCC so that they may be most appropriately counseled. PMID:12537653

  1. 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

  2. Comprehension.

    ERIC Educational Resources Information Center

    Bollenbach, Carolyn

    1986-01-01

    Teaching comprehension skills requires teaching to intuition with activities such as presenting puzzling situations to introduce a topic, using art to elicit latent feelings, using imagery and improvisations to enhance visualization, and using music and dance to encourage nonverbal expressions. (DB)

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

    PubMed

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

    2009-09-01

    Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network. PMID:19516255

  4. 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. PMID:19000078

  5. 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…

  6. 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

  7. 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

  8. 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.

  9. Comprehensive risk assessment of heavy metals in lake sediment from public parks in Shanghai.

    PubMed

    Yang, Jing; Chen, Ling; Liu, Li-Zao; Shi, Wei-Ling; Meng, Xiang-Zhou

    2014-04-01

    Rapid urbanization has caused potential pollution of heavy metal in Shanghai. A comprehensive pollution study of heavy metals (Cd, Cu, Pb, and Zn) in 35 lake surface sediments from city parks in the four different urbanized areas of Shanghai was conducted. Intensive human activities caused moderate enrichment of the four metals in highly urbanized areas, especially Cd with the significant enrichment in the central urban core area. However, the levels of the four metals in all the sediments were lower than the corresponding consensus-based Probable Effect Concentration, indicating adverse effects not to occur frequently. The integrated pollution assessments of multiple heavy metals also suggested low ecological risk and 15-29 percent probability of toxicity in most of sediments. The metal speciation analysis showed that Cd, Cu, Pb, and Zn were dominated by the non-residual fractions and thus they have high mobility and bioavailability, indicating significant anthropogenic sources. According to the Risk Assessment Code, Cd had the highest bioavailable fraction and represented high or very high risk, followed by Zn with medium or high risks in most of samples, while no or low risk was found for Cu and Pb at most sites because they were dominated by reducible and residual fractions. Correlation analysis showed that chemical fractions of heavy metals were prone to transform among each other if environmental conditions changed. Therefore, in view of anthropogenic inputs and speciation distribution, heavy metals with very high bioavailability at very low total levels and those with low bioavailability at very high total levels should not be ignored. PMID:24530728

  10. 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…

  11. Bridging Student Health Risks and Academic Achievement through Comprehensive School Health Programs.

    ERIC Educational Resources Information Center

    Symons, Cynthia Wolford; Cinelli, Bethann; James, Tammy C.; Groff, Patti

    1997-01-01

    Research confirms a direct link between student health risk behavior and education outcomes, education behaviors, and student attitudes. This article discusses barriers to comprehensive school health programming; summarizes relevant information concerning several health-risk behaviors (intentional injuries, diet, physical activity, sexual-risk…

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

    PubMed

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

    2009-08-01

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

  13. Comprehensive risk assessment for early neurologic complications after liver transplantation

    PubMed Central

    Wu, Si-Yuan; Chen, Teng-Wei; Feng, An-Chieh; Fan, Hsiu-Lung; Hsieh, Chung-Bao; Chung, Kuo-Piao

    2016-01-01

    AIM: To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon. METHODS: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis. RESULTS: In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients’ age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m2, Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174. CONCLUSION: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation. PMID:27350733

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

    PubMed

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

    2013-11-22

    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

  15. 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

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

    PubMed

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

    2013-12-30

    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

  17. 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

  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. 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

  20. 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. PMID:26817782

  1. 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…

  2. Comprehensive safeguards evaluation methods and societal risk analysis

    SciTech Connect

    Richardson, J.M.

    1982-03-01

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

  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. PMID:24444518

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

    NASA Astrophysics Data System (ADS)

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

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

  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. 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.

  7. 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

  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. [Comprehensive Risk Assessment of Soil Heavy Metals Based on Monte Carlo Simulation and Case Study].

    PubMed

    Yang, Yang; Dai, Dan; Cai, Yi-min; Chen, Wei-ping; Hou, Yu; Yang, Feng

    2015-11-01

    Based on the stochastic. theory, the Monte Carlo simulation was introduced in ecological risk assessment and health risk assessment. Together with the multi-statistical technique, the proposed models were used for risk analysis in the Bin-Chang Coal Chemical industry park. The results showed that high levels of Cd, Co, and Cr were found in the area with long time mining. The comprehensive single index and comprehensive risk index showed that the ecological risk of soil metals fell into the poor level, with probabilities of 53.2% and 55.6%, respectively. The health risk caused by hand to mouth ingestion was significantly greater than that by dermal exposure, and Cr was of prime concern for pollution control. Children were taking a major health risk. Their non-cancer risks were maintained at a high level, and 5.0-fold higher than adults under hand to mouth ingestion, and 8.2-fold higher than adults under dermal exposure. The cancer risk for children under these two exposure ways were both above the safety standard suggested by USEPA. PMID:26911013

  10. Effectiveness of Corrective Reading on Reading Comprehension and Fluency in At-Risk Students

    ERIC Educational Resources Information Center

    Weaver, Barbara Jean Alexander

    2012-01-01

    One of the greatest predictors and characteristics of a high school dropout has been poor reading skills. Students with low achievement levels in reading by the end of third grade are at greater risk of becoming a dropout. The study sought to determine whether the Corrective Reading Program impacted reading comprehension and fluency skills of…

  11. Comprehensive Early Intervention Program for High-Risk Infants, Toddlers and Their Families: Research Implications.

    ERIC Educational Resources Information Center

    Fahs, Mary Ellen; And Others

    The Center for Comprehensive Health Practice in the East Harlem area of New York City operates an early intervention program called the Infant School to promote the healthy development of high-risk children from birth to 2 years of age, including those of mothers who had been users of cocaine and/or crack. The Infant School curriculum is designed…

  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. 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…

  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. 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.

  16. Dynamic Visual Support for Story Comprehension and Mental Model Building by Young, At-Risk Children.

    ERIC Educational Resources Information Center

    Sharp, Diane L. M.; And Others

    1995-01-01

    Compares results of story telling to kindergarten students using text only, helpful video, and minimal video. Results indicate that multimedia technologies are valuable tools for supporting the development of story comprehension, mental model building, and literacy in young children who are at-risk for school failure. Sample stories used in…

  17. Promoting At-Risk Preschool Children's Comprehension through Research-Based Strategy Instruction

    ERIC Educational Resources Information Center

    DeBruin-Parecki, Andrea; Squibb, Kathryn

    2011-01-01

    Young children living in poor urban neighborhoods are often at risk for reading difficulties, in part because developing listening comprehension strategies and vocabulary knowledge may not be a priority in their prekindergarten classrooms, whose curriculums typically focus heavily on phonological awareness and alphabet knowledge. Prereading…

  18. 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…

  19. 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.

  20. 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...

  1. Information for People Treated with Human Growth Hormone (Comprehensive Report)

    MedlinePlus

    ... I help with the follow-up study? How did Creutzfeldt-Jakob disease (CJD) occur in people treated ... help to clarify individual level of risk. [ Top ] Did the hormone I took cause CJD? We have ...

  2. 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. PMID:26311042

  3. Endocrine disrupters: a human risk?

    PubMed

    Waring, R H; Harris, R M

    2005-12-01

    Endocrine disrupters (EDs) alter normal hormonal regulation and may be naturally occurring or environmental contaminants. Classically, EDs act genomically, with agonistic or antagonistic effects on steroid receptors and may alter reproductive function and/or cause feminisation by binding to oestrogen or androgen receptors; their binding to the thyroid receptor may dysregulate the neuroendocrine system. Recently, it has been shown that EDs can also act by non-genomic mechanisms, altering steroid synthesis (inhibition of cytochrome P450 isoforms) or steroid metabolism. The alkylphenol and phthalate plasticisers inhibit the inactivation of oestrogens by sulphation (via SULT 1A1 and 1E1 isoforms) and so cause a rise in levels of the free active endogenous oestrogens. A range of ED effects have been shown in mammals, fish, birds, reptiles, amphibia and aquatic invertebrates but it is not yet clear whether these processes also occur in human beings. It is evident that EDs, as well as altering reproduction, can cause changes in neurosteroid levels and so have the potential to affect immune function, behaviour and memory. This may be of long-term concern since traces of EDs such as plasticisers, brominated fire retardants, sunscreen agents and cosmetic ingredients are widely distributed in the environment and in human biofluids. PMID:16271281

  4. Moving Forward in Human Cancer Risk Assessment

    PubMed Central

    Paules, Richard S.; Aubrecht, Jiri; Corvi, Raffaella; Garthoff, Bernward; Kleinjans, Jos C.

    2011-01-01

    Background The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks. Objectives We provide a response to a growing appeal for a paradigm change in human cancer risk assessment. Methods To facilitate development of a road map for this needed paradigm change in carcinogenicity testing, a workshop titled “Genomics in Cancer Risk Assessment” brought together toxicologists from academia and industry and government regulators and risk assessors from the United States and the European Union. Participants discussed the state-of-the-art in developing alternative testing strategies for carcinogenicity, with emphasis on potential contributions from omics technologies. Results and Conclusions The goal of human risk assessment is to decide whether a given exposure to an agent is acceptable to human health and to provide risk management measures based on evaluating and predicting the effects of exposures on human health. Although exciting progress is being made using genomics approaches, a new paradigm that uses these methods and human material when possible would provide mechanistic insights that may inform new predictive approaches (e.g., in vitro assays) and facilitate the development of genomics-derived biomarkers. Regulators appear to be willing to accept such approaches where use is clearly defined, evidence is strong, and approaches are qualified for regulatory use. PMID:21147607

  5. 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.…

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

    PubMed Central

    Zhang, Yan; Zhong, Ming

    2013-01-01

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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Relative effectiveness of comprehensive community programming for drug abuse prevention with high-risk and low-risk adolescents.

    PubMed

    Johnson, C A; Pentz, M A; Weber, M D; Dwyer, J H; Baer, N; MacKinnon, D P; Hansen, W B; Flay, B R

    1990-08-01

    This article reviews major risk factors for cigarette smoking, alcohol, and other drug abuse and promising community-based approaches to primary prevention. In a longitudinal experimental study, 8 representative Kansas City communities were assigned randomly to program (school, parent, mass media, and community organization) and control (mass media and community organization only) conditions. Programs were delivered at either 6th or 7th grade, and panels were followed through Grade 9 or 10. The primary findings were (a) significant reductions at 3 years in tobacco and marijuana use and (b) equivalent reductions for youth at different levels of risk. This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk. PMID:2212182

  12. 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.

  13. HUMAN EXPOSURE MODELING FOR CUMULATIVE RISK

    EPA Science Inventory

    US EPA's Office of Research and Development (ORD) has identified cumulative risk assessment as a priority research area. This is because humans and other organisms are exposed to a multitude of chemicals, physical agents, and other stressors through multiple pathways, routes, an...

  14. Comprehensive nucleosome mapping of the human genome in cancer progression

    PubMed Central

    Druliner, Brooke R.; Vera, Daniel; Johnson, Ruth; Ruan, Xiaoyang; Apone, Lynn M.; Dimalanta, Eileen T.; Stewart, Fiona J.; Boardman, Lisa; Dennis, Jonathan H.

    2016-01-01

    Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation. PMID:26735342

  15. 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. PMID:26428667

  16. 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

  17. 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. PMID:18772890

  18. Comprehension of human communicative signs in pet dogs (Canis familiaris).

    PubMed

    Soproni, K; Miklósi, A; Topál, J; Csányi, V

    2001-06-01

    On the basis of a study by D. J. Povinelli, D. T. Bierschwale, and C. G. Cech (1999), the performance of family dogs (Canis familiaris) was examined in a 2-way food choice task in which 4 types of directional cues were given by the experimenter: pointing and gazing, head-nodding ("at target"), head turning above the correct container ("above target"), and glancing only ("eyes only"). The results showed that the performance of the dogs resembled more closely that of the children in D. J. Povinelli et al.'s study, in contrast to the chimpanzees' performance in the same study. It seems that dogs, like children, interpret the test situation as being a form of communication. The hypothesis is that this similarity is attributable to the social experience and acquired social routines in dogs because they spend more time in close contact with humans than apes do, and as a result dogs are probably more experienced in the recognition of human gestures. PMID:11459158

  19. 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. PMID:26330482

  20. 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

  1. 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

  2. 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.

  3. Comprehensive Risk-Based Diagnostically Driven Treatment Planning: Developing Sequentially Generated Treatment.

    PubMed

    Kois, Dean E; Kois, John C

    2015-07-01

    The clinical example presented in this article demonstrates a risk-based, diagnostically driven treatment planning approach by focusing on 4 key categories: periodontal, biomechanical, functional, dentofacial. In addition, our unique approach allowed the comprehensive clinical management of a patient with complex restorative needs. A full-mouth rehabilitation was completed sequentially without sacrificing the amount of dentistry necessary to restore health, comfort, function, and esthetics. The result exceeded the patient's expectation and was made financially possible by extending treatment over numerous years. PMID:26140967

  4. 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.

  5. 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).

  6. 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

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

    PubMed

    Oakman, Jodi; Macdonald, Wendy; Wells, Yvonne

    2014-11-01

    This study of selected jobs in the health care sector explored a range of physical and psychosocial factors to identify those that most strongly predicted work-related musculoskeletal disorders (WMSD) risk. A self-report survey was used to collect data on physical and psychosocial risk factors from employees in three health care organisations in Victoria, Australia. Multivariate analyses demonstrated the importance of both psychosocial and physical hazards in predicting WMSD risk and provides evidence for risk management of WMSDs to incorporate a more comprehensive and integrated approach. Use of a risk management toolkit is recommended to address WMSD risk in the workplace. PMID:24998863

  8. 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.

  9. 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. PMID:12577903

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

    SciTech Connect

    Duncan, Ian

    2014-08-31

    , 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.

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

    PubMed

    Yamashita, Shunichi

    2014-06-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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)

  16. 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

  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 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.

  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. The Correlation between the Three Reading Fluency Subskills and Reading Comprehension in At-Risk Adolescent Readers

    ERIC Educational Resources Information Center

    Courbron, Craig

    2012-01-01

    The purpose of this study was to determine which of the three reading fluency subskills were most strongly correlated with reading comprehension in adolescent at-risk readers. The participants were 82 adolescent males (ages 13-19) who had been committed to a juvenile detention facility. Archival data from a two-year period was collected from a…

  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. 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. PMID:27176764

  3. Risk and the evolution of human exchange

    PubMed Central

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

    2012-01-01

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

  4. Risk and the evolution of human exchange.

    PubMed

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

    2012-08-01

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

  5. 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…

  6. 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...

  7. 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…

  8. 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...

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. A risk methodology to evaluate sensitvity of plant risk to human errors

    SciTech Connect

    Samanta, P.; Wong, S.; Higgins, J.; Haber, S.; Luckas, W.

    1988-01-01

    This paper presents an evaluation of sensitivity of plant risk parameters, namely the core melt frequency and the accident sequence frequencies, to the human errors involved in various aspects of nuclear power plant operations. Results are provided using the Oconee-3 Probabilistic Risk Assessment model as an example application of the risk methodology described herein. Sensitivity analyses in probabilistic risk assessment (PRA) involve three areas: (1) a determination of the set of input parameters; in this case, various categories of human errors signifying aspects of plant operation, (2) the range over which the input parameters vary, and (3) an assessment of the sensitivity of the plant risk parameters to the input parameters which, in this case, consist of all postulated human errors, or categories of human errors. The methodology presents a categorization scheme where human errors are categorized in terms of types of activity, location, personnel involved, etc., to relate the significance of sensitivity of risk parameters to specific aspects of human performance in the nuclear plant. Ranges of variability for human errors have been developed considering the various known causes of uncertainty in human error probability estimates in PRAs. The sensitivity of the risk parameters are assessed using the event/fault tree methodology of the PRA. The results of the risk-based sensitivity evaluation using the Oconee-3 PRA as an example show the quantitative impact on the plant risk level due to variations in human error probabilities. The relative effects of various human error categories and human error sorts within the categories are also presented to identify and characterize significant human errors for effective risk management in nuclear power plant operational activities. 8 refs., 10 figs., 4 tabs.

  18. 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. PMID:26448058

  19. MULTIMEDIA HUMAN EXPOSURE AND RISK ASSESSMENT MODELING

    EPA Science Inventory

    Exposures and health risk comparisons from different sites may be used for allocating limited resources available for remedial action. It is important that comparisons between different sites use similar levels of site-specific data and/or screening level data. Risk assessment c...

  20. 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.

  1. 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.

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

    PubMed Central

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

    2004-01-01

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

  3. 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.

  4. 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 ...

  5. 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. PMID:27046140

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

    PubMed Central

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

    2013-01-01

    Introduction Current risk assessment concepts in ST-elevation myocardial infarction (STEMI) are suboptimal for guiding clinical management. Aim To elaborate a composite risk management concept for STEMI, enhancing clinical decision making. Material and methods 1995 unselected, registry patients with STEMI treated with primary percutaneous coronary intervention (pPCI) (mean age 60.1 years, 72.1% men) were included in the study. The independent risk markers were grouped by means of factor analysis, and the appropriate hazards were identified. Results In-hospital death was the primary outcome, observed in 95 (4.7%) patients. Independent predictors of mortality included age, leukocytosis, hyperglycemia, tachycardia, low blood pressure, impaired renal function, Killip > 1, anemia, and history of coronary disease. The factor analysis identified two significant clusters of risk markers: 1. age-anemia- impaired renal function, interpreted as the patient-related hazard; and 2. tachycardia-Killip > 1-hyperglycemia-leukocytosis, interpreted as the event-related (hemodynamic) hazard. The hazard levels (from low to high) were defined based on the number of respective risk markers. Patient-related hazard determined outcomes most significantly within the low hemodynamic hazard group. Conclusions The dissection of the global risk into the combination of patient- and event-related (hemodynamic) hazards allows comprehensive assessment and management of several, often contradictory sources of risk in STEMI. The cohort of high-risk STEMI patients despite hemodynamically trivial infarction face the most suboptimal outcomes under the current invasive management strategy. PMID:24570721

  7. 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...

  8. 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.

  9. HUMAN HEALTH RISK EVALUATION OF WEATHERED TOXAPHENE

    EPA Science Inventory

    Coastal/estuarine sediments are repositories for persistent organic pollutants (POPs). Sediment-associated POPs such as the chlorinated pesticide toxaphene accumulate in aquatic wildlife with the potential for transferred to higher organisms (fish, marine mammals, birds, humans) ...

  10. 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

  11. A Comprehensive, High-Resolution Genomic Transcript Map of Human Skeletal Muscle

    PubMed Central

    Bortoluzzi, Stefania; Rampoldi, Luca; Simionati, Barbara; Zimbello, Rosanna; Barbon, Alessandro; d’Alessi, Fabio; Tiso, Natascia; Pallavicini, Alberto; Toppo, Stefano; Cannata, Nicola; Valle, Giorgio; Lanfranchi, Gerolamo; Danieli, Gian Antonio

    1998-01-01

    We present the Human Muscle Gene Map (HMGM), the first comprehensive and updated high-resolution expression map of human skeletal muscle. The 1078 entries of the map were obtained by merging data retrieved from UniGene with the RH mapping information on 46 novel muscle transcripts, which showed no similarity to any known sequence. In the map, distances are expressed in megabase pairs. About one-quarter of the map entries represents putative novel genes. Genes known to be specifically expressed in muscle account for <4% of the total. The genomic distribution of the map entries confirmed the previous finding that muscle genes are selectively concentrated in chromosomes 17, 19, and X. Five chromosomal regions are suspected to have a significant excess of muscle genes. Present data support the hypothesis that the biochemical and functional properties of differentiated muscle cells may result from the transcription of a very limited number of muscle-specific genes along with the activity of a large number of genes, shared with other tissues, but showing different levels of expression in muscle. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. F23198–F23242.] PMID:9724327

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

    PubMed Central

    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/. PMID:25505144

  13. 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. PMID:24803509

  14. Comprehensive Reconstruction and Visualization of Non-Coding Regulatory Networks in Human

    PubMed Central

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

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape. PMID:25540777

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

    PubMed

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

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape. PMID:25540777

  16. 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.

  17. 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

  18. Recruitment Methods and Show Rates to a Prostate Cancer Early Detection Program for High-Risk Men: A Comprehensive Analysis

    PubMed Central

    Giri, Veda N.; Coups, Elliot J.; Ruth, Karen; Goplerud, Julia; Raysor, Susan; Kim, Taylor Y.; Bagden, Loretta; Mastalski, Kathleen; Zakrzewski, Debra; Leimkuhler, Suzanne; Watkins-Bruner, Deborah

    2009-01-01

    Purpose Men with a family history (FH) of prostate cancer (PCA) and African American (AA) men are at higher risk for PCA. Recruitment and retention of these high-risk men into early detection programs has been challenging. We report a comprehensive analysis on recruitment methods, show rates, and participant factors from the Prostate Cancer Risk Assessment Program (PRAP), which is a prospective, longitudinal PCA screening study. Materials and Methods Men 35–69 years are eligible if they have a FH of PCA, are AA, or have a BRCA1/2 mutation. Recruitment methods were analyzed with respect to participant demographics and show to the first PRAP appointment using standard statistical methods Results Out of 707 men recruited, 64.9% showed to the initial PRAP appointment. More individuals were recruited via radio than from referral or other methods (χ2 = 298.13, p < .0001). Men recruited via radio were more likely to be AA (p<0.001), less educated (p=0.003), not married or partnered (p=0.007), and have no FH of PCA (p<0.001). Men recruited via referrals had higher incomes (p=0.007). Men recruited via referral were more likely to attend their initial PRAP visit than those recruited by radio or other methods (χ2 = 27.08, p < .0001). Conclusions This comprehensive analysis finds that radio leads to higher recruitment of AA men with lower socioeconomic status. However, these are the high-risk men that have lower show rates for PCA screening. Targeted motivational measures need to be studied to improve show rates for PCA risk assessment for these high-risk men. PMID:19758657

  19. Improving Reading Comprehension of At-Risk High-School Students: The ART of Reading Program

    ERIC Educational Resources Information Center

    McCallum, R. Steve; Krohn, Katherine R.; Skinner, Christopher H.; Hilton-Prillhart, Angela; Hopkins, Michael; Waller, Steven; Polite, Fritz

    2011-01-01

    Participants (115 low-socioeconomic-status [SES], inner-city, high-school students) were exposed to three reading conditions: (1) a control condition in which students silently read brief selected passages; (2) an experimental condition in which students were prompted to perform a three-part (Ask, Read, and Tell [ART]) comprehension enhancement…

  20. 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…

  1. 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...

  2. 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.

  3. Environmental Epigenetics: Potential Application in Human Health Risk Assessment

    EPA Science Inventory

    Although previous studies have shown a significant involvement of epigenetic dysregulation in human diseases, the applicability of epigenetic data in the current human health risk assessment paradigm is unclear. The goals of this study are to compare the relative sensitivities of...

  4. 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

  5. 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

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

    PubMed

    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 mm(2) with single scan and 7 × 8 mm(2) for multiple scans), while the second is of the high lateral resolution (5 μm) and a narrow field of view (1.5 × 1.2 mm(2) 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. PMID:22029360

  7. 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.

  8. 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…

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

    NASA Technical Reports Server (NTRS)

    Hamlin, Teri L.

    2010-01-01

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

  10. Studying Risk Factors Associated with Human Leptospirosis

    PubMed Central

    Kamath, Ramachandra; Swain, Subhashisa; Pattanshetty, Sanjay; Nair, N Sreekumaran

    2014-01-01

    Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression) was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA) to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0), presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02) and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73) and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67) were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still considered as

  11. 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

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

    PubMed

    Viney, William; Callard, Felicity; Woods, Angela

    2015-06-01

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

  13. Adapting a Comprehensive Approach to African American Women's Sexual Risk Taking.

    ERIC Educational Resources Information Center

    Wyatt, Gail E.; Tucker, M. Belinda; Romero, Gloria J.; Carmona, Jennifer Vargas; Newcomb, Michael D.; Wayment, Heidi A.; Loeb, Tamra Burns; Solis, Beatriz M.; Mitchell-Kernan, Claudia

    1997-01-01

    Examined factors predicting the context of HIV-related sexual behaviors in African American women. Surveys investigated demographics; sexual history, behavior, attitudes, risk, and communication; drug use; contraception; and risk reduction efforts since Magic Johnson's HIV disclosure. Demographics, sexual communication, and past sexual experiences…

  14. 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.

  15. 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

  16. Genetic Variants Associated with Breast Cancer Risk: Comprehensive Field Synopsis, Meta-Analysis, and Epidemiologic Evidence

    PubMed Central

    Zhang, Ben; Beeghly-Fadiel, Alicia; Long, Jirong; Zheng, Wei

    2011-01-01

    SUMMARY Background Over 1,000 reports have been published during the past two decades on associations between genetic variants in candidate genes and breast cancer risk. Results have been generally inconsistent. We conducted literature searches and meta-analyses to provide a field synopsis of the current understanding of the genetic architecture of breast cancer risk. Methods Systematic literature searches for candidate gene association studies of breast cancer risk were conducted in two stages using PubMed on or before February 28, 2010. A total of 24,500 publications were identified, of which, 1,059 were deemed eligible for inclusion. Meta-analyses were conducted for 279 genetic variants in 128 candidate genes or chromosomal loci that had a minimum of three data sources available. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast cancer risk. Findings Fifty-one variants in 40 genes showed statistically significant associations with breast cancer risk. Cumulative epidemiologic evidence for an association with breast cancer risk was graded as strong for 10 variants in six genes (ATM, CASP8, CHEK2, CTLA4, NBN, and TP53), moderate for four variants in four genes (ATM, CYP19A1, TERT, and XRCC3), and weak for 37 additional variants. Additionally, in meta-analyses that included a minimum of 10,000 cases and 10,000 controls, convincing evidence of no association with breast cancer risk was identified for 45 variants in 37 genes. Interpretation While most genetic variants evaluated in previous candidate gene studies showed no association with breast cancer risk in meta-analyses, 14 variants in 9 genes were found to have moderate to strong evidence for an association with breast cancer risk. Further evaluation of these variants is warranted. PMID:21514219

  17. [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. PMID:27232494

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

    PubMed Central

    Okada, Kazue; Kimura, Taichi; Piao, Jinhua; Tanaka, Shinya; Shinohara, Yasuro

    2015-01-01

    Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response. PMID:26132161

  19. Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

    PubMed

    Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

    2016-04-26

    The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles. PMID:27050271

  20. Comprehensive Longitudinal Study Challenges the Existence of Neonatal Imitation in Humans.

    PubMed

    Oostenbroek, Janine; Suddendorf, Thomas; Nielsen, Mark; Redshaw, Jonathan; Kennedy-Costantini, Siobhan; Davis, Jacqueline; Clark, Sally; Slaughter, Virginia

    2016-05-23

    Human children copy others' actions with high fidelity, supporting early cultural learning and assisting in the development and maintenance of behavioral traditions [1]. Imitation has long been assumed to occur from birth [2-4], with influential theories (e.g., [5-7]) placing an innate imitation module at the foundation of social cognition (potentially underpinned by a mirror neuron system [8, 9]). Yet, the very phenomenon of neonatal imitation has remained controversial. Empirical support is mixed and interpretations are varied [10-16], potentially because previous investigations have relied heavily on cross-sectional designs with relatively small samples and with limited controls [17, 18]. Here, we report surprising results from the most comprehensive longitudinal study of neonatal imitation to date. We presented infants (n = 106) with nine social and two non-social models and scored their responses at 1, 3, 6, and 9 weeks of age. Longitudinal analyses indicated that the infants did not imitate any of the models, as they were just as likely to produce the gestures in response to control models as they were to matching models. Previous positive findings were replicated in limited cross-sections of the data, but the overall analyses confirmed these findings to be mere artifacts of restricted comparison conditions. Our results undermine the idea of an innate imitation module and suggest that earlier studies reporting neonatal imitation were methodologically limited. PMID:27161497

  1. A Comprehensive Computational Study of the Interaction between Human Serum Albumin and Fullerenes.

    PubMed

    Leonis, Georgios; Avramopoulos, Aggelos; Papavasileiou, Konstantinos D; Reis, Heribert; Steinbrecher, Thomas; Papadopoulos, Manthos G

    2015-12-01

    Human serum albumin (HSA) is the most abundant blood plasma protein, which transports fatty acids, hormones, and drugs. We consider nanoparticle-HSA interactions by investigating the binding of HSA with three fullerene analogs. Long MD simulations, quantum mechanical (fragment molecular orbital, energy decomposition analysis, atoms-in-molecules), and free energy methods elucidated the binding mechanism in these complexes. Such a systematic study is valuable due to the lack of comprehensive theoretical approaches to date. The main elements of the mechanism include the following: binding to IIA site results in allosteric modulation of the IIIA and heme binding sites with an increase in α-helical structure of IIIA. Fullerenes displayed high binding affinities for HSA; therefore, HSA can be used as a fullerene carrier, facilitating any toxic function the fullerene may exert. Complex formation is driven by hydrogen bonding, van der Waals, nonpolar, charge transfer, and dispersion energy contributions. Proper functionalization of C60 has enhanced its binding to HSA by more than an order of magnitude. This feature may be important for biological applications (e.g., photodynamic therapy of cancer). Satisfactory agreement with relevant experimental and theoretical data has been obtained. PMID:26523956

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

    PubMed

    Frenk, Julio; Gómez-Dantés, Octavio

    2015-01-01

    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. PMID:26766859

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

    PubMed Central

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

    2013-01-01

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

  4. 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

  5. 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. PMID:27144161

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

    PubMed Central

    2013-01-01

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

  7. 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. PMID:25070413

  8. 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

  9. A comprehensive examination of breast cancer risk loci in African American women.

    PubMed

    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

    2014-10-15

    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

  10. 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

  11. DYT1 dystonia increases risk taking in humans.

    PubMed

    Arkadir, David; Radulescu, Angela; Raymond, Deborah; Lubarr, Naomi; Bressman, Susan B; Mazzoni, Pietro; Niv, Yael

    2016-01-01

    It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans. PMID:27249418

  12. Risk of bleeding associated with interventional musculoskeletal radiology procedures. A comprehensive review of the literature.

    PubMed

    Foremny, Gregory B; Pretell-Mazzini, Juan; Jose, Jean; Subhawong, Ty K

    2015-05-01

    This review compiles the current literature on the bleeding risks in common musculoskeletal interventional procedures and attempts to provide guidance for practicing radiologists in making decisions regarding the periprocedural management of patients on antithrombotic therapy. The practitioner must weigh the risk of bleeding if therapy is continued against the possibility a thromboembolic occurring if anticoagulation therapy is withheld or reversed. Unfortunately, there is little empirical data to guide evidence-based decisions for many musculoskeletal interventions. However, a review of the literature shows that for low-risk procedures, such as arthrograms/arthrocenteses or muscle/tendon sheath injections, bleeding risks are sufficiently small that anticoagulants and antiplatelet therapies need not be withheld. Additionally, relatively higher-risk procedures, such as needle biopsies of bone and soft tissue, may be safely performed without holding antithrombotic therapy, provided pre-procedural INR is within therapeutic range. Thus, while a patient's particular clinical circumstances should dictate optimal individualized management, anticoagulation alone is not a general contraindication to most interventional musculoskeletal radiology procedures. PMID:25433718

  13. Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: a comprehensive epidemiological assessment from India.

    PubMed

    Mamidala, Madhu Poornima; Polinedi, Anupama; P T V, Praveen Kumar; Rajesh, N; Vallamkonda, Omsai Ramesh; Udani, Vrajesh; Singhal, Nidhi; Rajesh, Vidya

    2013-09-01

    Incidence of Autism Spectrum Disorder (ASD) is increasing across the globe and no data is available from India regarding the risk factors of ASD. In this regard a questionnaire based epidemiological assessment was carried out on prenatal, perinatal and neonatal risk factors of ASD across 8 cities in India. A retrospective cohort of 942 children was enrolled for the study. 471 children with ASD, under age of 10, were analyzed for pre-, peri-, and neonatal factors and were compared with the observations from equal number of controls. The quality control of the questionnaire and data collection was done thoroughly and the observations were computed statistically. A total of 25 factors were evaluated by unadjusted and adjusted analysis in this study. Among the prenatal factors considered, advanced maternal age, fetal distress and gestational respiratory infections were found to be associated with ASD and had an odds ratio of 1.8. Evaluation of perinatal and neonatal risk factors showed labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia to be associated with ASD with an odds ratio greater than 1.5. This important study, first of its kind in Indian population gives a firsthand account of the relation of pre-, peri- and neonatal risk factors on ASD from an ethnically and socially diverse country like India, the impact of which was unknown earlier. This advocates additional focused investigations on physiological and genetic changes contributed by these risk factor inducing environments. PMID:23816633

  14. 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.

  15. Effect of dietary Fatty acids on human lipoprotein metabolism: a comprehensive update.

    PubMed

    Ooi, Esther M M; Watts, Gerald F; Ng, Theodore W K; Barrett, P Hugh R

    2015-06-01

    Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids. PMID:26043038

  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 milk biomonitoring data: interpretation and risk assessment issues.

    PubMed

    LaKind, Judy S; Brent, Robert L; Dourson, Michael L; Kacew, Sam; Koren, Gideon; Sonawane, Babasaheb; Tarzian, Anita J; Uhl, Kathleen

    2005-10-22

    Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person's body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant's exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a "dose" from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of "risk assessment" as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental

  18. A comprehensive review of the Kumbh Mela: identifying risks for spread of infectious diseases.

    PubMed

    Sridhar, S; Gautret, P; Brouqui, P

    2015-02-01

    The Kumbh Mela in India is the largest mass gathering in the world which witnessed close to 100 million visitors in 2013. An event of this magnitude presents challenges. Increased population density, reduced hygienic conditions and exposure to environmental pollutants pave the way for easy transmission of pathogens. Due to the possibility of epidemics, the primary focus should be on identifying the potential risk factors and implementing appropriate preventive measures. The context of religion and psychology of the pilgrims is also closely associated with the evolution of the risk factors and so forms an important part of the discussion. We provide a brief background to the Kumbh Mela with a description of the existing and potential risk factors that require our attention. PMID:25682278

  19. The risk factors for human cysticercosis in Mbulu District, Tanzania.

    PubMed

    Mwang'onde, Beda J; Nkwengulila, Gamba; Chacha, Mwita

    2014-01-01

    The objective of this study was to explore the reasons for the persistence of human cysticercosis (HCC) transmission in Mbulu District, northern Tanzania. The study was carried out in 25 villages, whereby five major risks were identified. The risks were indiscriminate defaecation and improper use of toilets; a free-range system of keeping pigs; indiscriminate or unregulated slaughtering and inadequate meat hygiene and inspection; consumption of undercooked and porcine cysticerci infected pork; and social structure and roles. All of the identified risks were backed up by the immanent lifestyles of the community involved. These findings are important for the development of intervention strategies in the study area. PMID:25005750

  20. 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

  1. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine

    PubMed Central

    Subbiah, Vivek; Wagner, Michael J.; McGuire, Mary F.; Sarwari, Nawid M.; Devarajan, Eswaran; Lewis, Valerae O.; Westin, Shanon; Kato, Shumei; Brown, Robert E.; Anderson, Pete

    2015-01-01

    Background Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Patients and Methods Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. Results In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2–16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Conclusions Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized

  2. 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.

  3. Cardiovascular disease and risk factors in law enforcement personnel: a comprehensive review.

    PubMed

    Zimmerman, Franklin H

    2012-01-01

    Law enforcement is a high-stress occupation that is prone to increasing the prevalence and incidence of cardiovascular disease. Epidemiological studies suggest that police officers and related public safety personnel have an increased risk of cardiovascular morbidity and mortality. Currently employed police personnel have a high prevalence of traditional risk factors, including hypertension, hyperlipidemia, metabolic syndrome, cigarette smoking, and a sedentary lifestyle. Obesity may be more common in police officers compared with civilians, whereas diabetes is present less frequently. Law enforcement personnel are also exposed to occupation-specific risk factors that include sudden physical exertion, acute and chronic psychological stress, shift work, and noise. Workplace programs to promote the health and fitness of police officers are commonly lacking, but can be an effective means for reducing cardiovascular risk. Physicians should be familiar with the essential job tasks required for police officers to determine whether the individual is fit for duty. Governmental agencies have established strategic goals to reduce cardiovascular complications and improve the health and wellness of public safety personnel. PMID:22314143

  4. A comprehensive risk assessment framework for offsite transportation of inflammable hazardous waste.

    PubMed

    Das, Arup; Gupta, A K; Mazumder, T N

    2012-08-15

    A framework for risk assessment due to offsite transportation of hazardous wastes is designed based on the type of event that can be triggered from an accident of a hazardous waste carrier. The objective of this study is to design a framework for computing the risk to population associated with offsite transportation of inflammable and volatile wastes. The framework is based on traditional definition of risk and is designed for conditions where accident databases are not available. The probability based variable in risk assessment framework is substituted by a composite accident index proposed in this study. The framework computes the impacts due to a volatile cloud explosion based on TNO Multi-energy model. The methodology also estimates the vulnerable population in terms of disability adjusted life years (DALY) which takes into consideration the demographic profile of the population and the degree of injury on mortality and morbidity sustained. The methodology is illustrated using a case study of a pharmaceutical industry in the Kolkata metropolitan area. PMID:22633884

  5. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

    PubMed

    Shiotani, Akiko; Manabe, Noriaki; Kamada, Tomoari; Fujimura, Yoshinori; Sakakibara, Takashi; Haruma, Ken

    2012-04-01

    The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA. PMID:22486865

  6. 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…

  7. The Effects of a Computer Assisted Reading Program on the Oral Reading Fluency and Comprehension of At-Risk, Urban First Grade Students

    ERIC Educational Resources Information Center

    Gibson, Lenwood, Jr.

    2009-01-01

    The current investigation studied the effects of a computer software program of the oral reading fluency and comprehension of eight, first grade students. These students were identified as being either "at-risk" or "some-risk" for reading failure on the DIBELS oral reading fluency winter benchmark assessment. A multiple probe…

  8. 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…

  9. 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

  10. Statistical aspects and risks of human-caused earthquakes

    NASA Astrophysics Data System (ADS)

    Klose, C. D.

    2013-12-01

    The seismological community invests ample human capital and financial resources to research and predict risks associated with earthquakes. Industries such as the insurance and re-insurance sector are equally interested in using probabilistic risk models developed by the scientific community to transfer risks. These models are used to predict expected losses due to naturally occurring earthquakes. But what about the risks associated with human-caused earthquakes? Such risk models are largely absent from both industry and academic discourse. In countries around the world, informed citizens are becoming increasingly aware and concerned that this economic bias is not sustainable for long-term economic growth, environmental and human security. Ultimately, citizens look to their government officials to hold industry accountable. In the Netherlands, for example, the hydrocarbon industry is held accountable for causing earthquakes near Groningen. In Switzerland, geothermal power plants were shut down or suspended because they caused earthquakes in canton Basel and St. Gallen. The public and the private non-extractive industry needs access to information about earthquake risks in connection with sub/urban geoengineeing activities, including natural gas production through fracking, geothermal energy production, carbon sequestration, mining and water irrigation. This presentation illuminates statistical aspects of human-caused earthquakes with respect to different geologic environments. Statistical findings are based on the first catalog of human-caused earthquakes (in Klose 2013). Findings are discussed which include the odds to die during a medium-size earthquake that is set off by geomechanical pollution. Any kind of geoengineering activity causes this type of pollution and increases the likelihood of triggering nearby faults to rupture.

  11. 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.

  12. THE POLITICS OF RISK AND EU GOVERNANCE OF HUMAN MATERIAL

    PubMed Central

    Farrel, Anne-Maree

    2012-01-01

    This paper examines the politics of EU risk governance in relation to human material. It is argued that the political context has informed the way in which risks in relation to various types of human material have come to be defined as policy problems at EU level. In turn, this has influenced the design and/or persistence of institutional arrangements to manage such problems. It is further argued that this political context has resulted in a significant level of disconnection in risk governance in the area. This has happened in two ways. First, there has been a growing level of disconnection between institutional and stakeholder demands for a more expansive approach to risk governance in the area and the narrowly-circumscribed competence under Article 152(4)(a) EC, which permits the adoption of risk regulation regimes that set minimum standards of quality and safety in relation to blood, tissue/cells and organs. Second, it has led to the development of institutional arrangements that promote a bifurcated approach to risk governance, specifically in relation to blood and tissues/cells. Although a hybrid of traditional and new governance mechanisms have been employed to address this problem of disconnection, this has nevertheless added a further layer to already complex institutional arrangements for risk governance in the area. It is suggested that a more integrated approach to EU risk governance in relation to human material is needed. Implementing such an approach would contribute to greater clarity, transparency and accountability in decision-making processes, and this could enhance public trust in what is a politically-sensitive area of governance at EU level. PMID:23326180

  13. Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

    PubMed Central

    Wolff, Antonio C.; Blackford, Amanda L.; Visvanathan, Kala; Rugo, Hope S.; Moy, Beverly; Goldstein, Lori J.; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S.; Theriault, Richard L.; Hughes, Melissa E.; Weeks, Jane C.; Karp, Judith E.

    2015-01-01

    Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. PMID

  14. Human exposure, hazard and risk of alternative plasticizers to phthalate esters.

    PubMed

    Bui, Thuy T; Giovanoulis, Georgios; Cousins, Anna Palm; Magnér, Jörgen; Cousins, Ian T; de Wit, Cynthia A

    2016-01-15

    Alternative plasticizers to phthalate esters have been used for over a decade, but data regarding emissions, human exposure and health effects are limited. Here we review 20 alternative plasticizers in current use and their human exposure, hazard and risk. Physicochemical properties are collated for these diverse alternatives and log KOW values range over 15 orders of magnitude and log KAW and log KOA values over about 9 orders of magnitude. Most substances are hydrophobic with low volatility and are produced in high volumes for use in multiple applications. There is an increasing trend in the total use of alternative plasticizers in Sweden compared to common phthalate esters in the last 10 years, especially for DINCH. Evaluative indoor fate modeling reveals that most alternatives are distributed to vertical surfaces (e.g. walls or ceilings). Only TXIB and GTA are predicted to be predominantly distributed to indoor air. Human exposure data are lacking and clear evidence for human exposure only exists for DEHT and DINCH, which show increasing trends in body burdens. Human intake rates are collected and compared with limit values with resulting risk ratios below 1 except for infant's exposure to ESBO. PBT properties of the alternatives indicate mostly no reasons for concern, except that TEHPA is estimated to be persistent and TCP toxic. A caveat is that non-standard toxicological endpoint results are not available and, similar to phthalate esters, the alternatives are likely "pseudo-persistent". Key data gaps for more comprehensive risk assessment are identified and include: analytical methods to measure metabolites in biological fluids and tissues, toxicological information regarding non-standard endpoints such as endocrine disruption and a further refined exposure assessment in order to consider high risk groups such as infants, toddlers and children. PMID:26410720

  15. Human risk factors associated with pilots in runway excursions.

    PubMed

    Chang, Yu-Hern; Yang, Hui-Hua; Hsiao, Yu-Jung

    2016-09-01

    A breakdown analysis of civil aviation accidents worldwide indicates that the occurrence of runway excursions represents the largest portion among all aviation occurrence categories. This study examines the human risk factors associated with pilots in runway excursions, by applying a SHELLO model to categorize the human risk factors and to evaluate the importance based on the opinions of 145 airline pilots. This study integrates aviation management level expert opinions on relative weighting and improvement-achievability in order to develop four kinds of priority risk management strategies for airline pilots to reduce runway excursions. The empirical study based on experts' evaluation suggests that the most important dimension is the liveware/pilot's core ability. From the perspective of front-line pilots, the most important risk factors are the environment, wet/containment runways, and weather issues like rain/thunderstorms. Finally, this study develops practical strategies for helping management authorities to improve major operational and managerial weaknesses so as to reduce the human risks related to runway excursions. PMID:27344128

  16. Sensitivity of risk parameters to human errors for a PWR

    SciTech Connect

    Samanta, P.; Hall, R. E.; Kerr, W.

    1980-01-01

    Sensitivities of the risk parameters, emergency safety system unavailabilities, accident sequence probabilities, release category probabilities and core melt probability were investigated for changes in the human error rates within the general methodological framework of the Reactor Safety Study for a Pressurized Water Reactor (PWR). Impact of individual human errors were assessed both in terms of their structural importance to core melt and reliability importance on core melt probability. The Human Error Sensitivity Assessment of a PWR (HESAP) computer code was written for the purpose of this study.

  17. 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

  18. Credit scores, cardiovascular disease risk, and human capital

    PubMed Central

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E.

    2014-01-01

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

  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

    2014-12-01

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

  20. Children's exposure to harmful elements in toys and low-cost jewelry: characterizing risks and developing a comprehensive approach.

    PubMed

    Guney, Mert; Zagury, Gerald J

    2014-04-30

    Contamination problem in jewelry and toys and children's exposure possibility have been previously demonstrated. For this study, risk from oral exposure has been characterized for highly contaminated metallic toys and jewelry ((MJ), n=16) considering three scenarios. Total and bioaccessible concentrations of Cd, Cu, Ni, and Pb were high in selected MJ. First scenario (ingestion of parts or pieces) caused unacceptable risk for eight items for Cd, Ni, and/or Pb (hazard index (HI)>1, up to 75, 5.8, and 43, respectively). HI for ingestion of scraped-off material scenario was always <1. Finally, saliva mobilization scenario caused HI>1 in three samples (two for Cd, one for Ni). Risk characterization identified different potentially hazardous items compared to United States, Canadian, and European Union approaches. A comprehensive approach was also developed to deal with complexity and drawbacks caused by various toy/jewelry definitions, test methods, exposure scenarios, and elements considered in different regulatory approaches. It includes bioaccessible limits for eight priority elements (As, Cd, Cr, Cu, Hg, Ni, Pb, and Sb). Research is recommended on metals bioaccessibility determination in toys/jewelry, in vitro bioaccessibility test development, estimation of material ingestion rates and frequency, presence of hexavalent Cr and organic Sn, and assessment of prolonged exposure to MJ. PMID:24641994

  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. Flood hazard, vulnerability, and risk assessment for human life

    NASA Astrophysics Data System (ADS)

    Pan, T.; Chang, T.; Lai, J.; Hsieh, M.; Tan, Y.; Lin, Y.

    2011-12-01

    Flood risk assessment is an important issue for the countries suffering tropical cyclones and monsoon. Taiwan is located in the hot zone of typhoon tracks in the Western Pacific. There are three to five typhoons landing Taiwan every year. Typhoons and heavy rainfalls often cause inundation disaster rising with the increase of population and the development of social economy. The purpose of this study is to carry out the flood hazard, vulnerability and risk in term of human life. Based on the concept that flood risk is composed by flood hazard and vulnerability, a inundation simulation is performed to evaluate the factors of flood hazard for human life according to base flood (100-year return period). The flood depth, velocity and rising ratio are the three factors of flood hazards. Furthermore, the factors of flood vulnerability are identified in terms of human life that are classified into two main factors, residents and environment. The sub factors related to residents are the density of population and the density of vulnerable people including elders, youngers and disabled persons. The sub factors related to environment include the the number of building floors, the locations of buildings, the and distance to rescue center. The analytic hierarchy process (AHP) is adopted to determine the weights of these factors. The risk matrix is applied to show the risk from low to high based on the evaluation of flood hazards and vulnerabilities. The Tseng-Wen River watershed is selected as the case study because a serious flood was induced by Typhoon Morakot in 2009, which produced a record-breaking rainfall of 2.361mm in 48 hours in the last 50 years. The results of assessing the flood hazard, vulnerability and risk in term of human life could improve the emergency operation for flood disaster to prepare enough relief goods and materials during typhoon landing.

  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. Development of human epithelial cell systems for radiation risk assessment

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.

    1994-01-01

    The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

  5. Fifteen-Minute Comprehensive Alcohol Risk Survey: Reliability and Validity Across American Indian and White Adolescents

    PubMed Central

    Komro, Kelli A; Livingston, Melvin D; Kominsky, Terrence K; Livingston, Bethany J; Garrett, Brady A; Molina, Mildred Maldonado; Boyd, Misty L

    2015-01-01

    Objective: American Indians (AIs) suffer from significant alcohol-related health disparities, and increased risk begins early. This study examined the reliability and validity of measures to be used in a preventive intervention trial. Reliability and validity across racial/ethnic subgroups are crucial to evaluate intervention effectiveness and promote culturally appropriate evidence-based practice. Method: To assess reliability and validity, we used three baseline surveys of high school students participating in a preventive intervention trial within the jurisdictional service area of the Cherokee Nation in northeastern Oklahoma. The 15-minute alcohol risk survey included 16 multi-item scales and one composite score measuring key proximal, primary, and moderating variables. Forty-four percent of the students indicated that they were AI (of whom 82% were Cherokee), including 23% who reported being AI only (n = 435) and 18% both AI and White (n = 352). Forty-seven percent reported being White only (n = 901). Results: Scales were adequately reliable for the full sample and across race/ethnicity defined by AI, AI/White, and White subgroups. Among the full sample, all scales had acceptable internal consistency, with minor variation across race/ethnicity. All scales had extensive to exemplary test–retest reliability and showed minimal variation across race/ethnicity. The eight proximal and two primary outcome scales were each significantly associated with the frequency of alcohol use during the past month in both the cross-sectional and the longitudinal models, providing support for both criterion validity and predictive validity. For most scales, interpretation of the strength of association and statistical significance did not differ between the racial/ethnic subgroups. Conclusions: The results support the reliability and validity of scales of a brief questionnaire measuring risk and protective factors for alcohol use among AI adolescents, primarily members of the

  6. Moving Toward Comprehensive Acute Heart Failure Risk Assessment in the Emergency Department

    PubMed Central

    Collins, Sean P.; Storrow, Alan B.

    2013-01-01

    Nearly 700,000 emergency department (ED) visits were due to acute heart failure (AHF) in 2009. Most visits result in a hospital admission and account for the largest proportion of a projected $70 billion to be spent on heart failure care by 2030. ED-based risk prediction tools in AHF rarely impact disposition decision making. This is a major factor contributing to the 80% admission rate for ED patients with AHF, which has remained unchanged over the last several years. Self-care behaviors such as symptom monitoring, medication taking, dietary adherence, and exercise have been associated with decreased hospital readmissions, yet self-care remains largely unaddressed in ED patients with AHF and thus represents a significant lost opportunity to improve patient care and decrease ED visits and hospitalizations. Furthermore, shared decision making encourages collaborative interaction between patients, caregivers, and providers to drive a care path based on mutual agreement. The observation that “difficult decisions now will simplify difficult decisions later” has particular relevance to the ED, given this is the venue for many such issues. We hypothesize patients as complex and heterogeneous as ED patients with AHF may need both an objective evaluation of physiologic risk as well as an evaluation of barriers to ideal self-care, along with strategies to overcome these barriers. Combining physician gestalt, physiologic risk prediction instruments, an evaluation of self-care, and an information exchange between patient and provider using shared decision making may provide the critical inertia necessary to discharge patients home after a brief ED evaluation. PMID:24159563

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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. PMID:26749540

  13. 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.

  14. The chronometry of risk processing in the human cortex

    PubMed Central

    Symmonds, Mkael; Moran, Rosalyn J.; Wright, Nicholas D.; Bossaerts, Peter; Barnes, Gareth; Dolan, Raymond J.

    2013-01-01

    The neuroscience of human decision-making has focused on localizing brain activity correlating with decision variables and choice, most commonly using functional MRI (fMRI). Poor temporal resolution means these studies are agnostic in relation to how decisions unfold in time. Consequently, here we address the temporal evolution of neural activity related to encoding of risk using magnetoencephalography (MEG), and show modulations of electromagnetic power in posterior parietal and dorsomedial prefrontal cortex (DMPFC) which scale with both variance and skewness in a lottery, detectable within 500 ms following stimulus presentation. Electromagnetic responses in somatosensory cortex following this risk encoding predict subsequent choices. Furthermore, within anterior insula we observed early and late effects of subject-specific risk preferences, suggestive of a role in both risk assessment and risk anticipation during choice. The observation that cortical activity tracks specific and independent components of risk from early time-points in a decision-making task supports the hypothesis that specialized brain circuitry underpins risk perception. PMID:23970849

  15. Human impacts and the global distribution of extinction risk

    PubMed Central

    Davies, Richard G; Orme, C. David L; Olson, Valerie; Thomas, Gavin H; Ross, Simon G; Ding, Tzung-Su; Rasmussen, Pamela C; Stattersfield, Ali J; Bennett, Peter M; Blackburn, Tim M; Owens, Ian P.F; Gaston, Kevin J

    2006-01-01

    Understanding the global geographical distribution of extinction risk is a key challenge in conservation biology. It remains controversial, however, to what extent areas become threat hotspots simply because of high human impacts or due to predisposing ecological conditions. Limits to the taxonomic and geographical extent, resolution and quality of previously available data have precluded a full global assessment of the relative roles of these factors. Here, we use a new global database on the geographical distributions of birds on continents and continental islands to show that, after controlling for species richness, the best predictors of the global pattern of extinction risk are measures of human impact. Ecological gradients are of secondary importance at a global scale. The converse is true for individual biogeographic realms, within which variation in human impact is reduced and its influence on extinction risk globally is therefore underestimated. These results underline the importance of a global perspective on the mechanisms driving spatial patterns of extinction risk, and the key role of anthropogenic factors in driving the current extinction crisis. PMID:16901831

  16. A comprehensive risk assessment for tephra accumulation using easily accessible data: the example of Cotopaxi volcano (Ecuador)

    NASA Astrophysics Data System (ADS)

    Biass, Sébastien; Frischknecht, Corine; Dell'Oro, Luca; Senegas, Olivier; Bonadonna, Costanza

    2010-05-01

    In order to answer the needs of contingency planning, we present a GIS-based method for risk assessment of tephra deposits, which is flexible enough to work with datasets of variable precision and resolution depending on data availabilty. Due to the constant increase of population density around volcanoes and the large dispersal of tephra from volcanic plumes, a wide range of threats such as roof collapses, destruction of crops, blockage of vital lifelines and health problems concern even remote communities. In the field of disaster management, there is a general agreement that a global and incomplete method, subject to revision and improvements, is better than no information at all. In this framework, our method is able to provide fast and rough insights on possible eruptive scenarios and their potential consequences on surrounding populations with only few available data, which can easily be refined later. Therefore, the knowledge of both the expected hazard (frequency and magnitude) and the vulnerability of elements at risk are required by planners in order to produce efficient emergency planning prior to a crisis. The Cotopaxi volcano, one of Ecuador's most active volcanoes, was used to develop and test this method. Cotopaxi volcano is located 60 km south of Quito and threatens a highly populated valley. Based on field data, historical reports and the Smithsonian catalogue, our hazard assessment was carried out using the numerical model TEPHRA2. We first applied a deterministic approach that evolved towards a fully probabilistic method in order to account for the most likely eruptive scenarios as well as the variability of atmospheric conditions. In parallel, we carried out a vulnerability assessment of the physical (crops and roofs), social (populations) and systemic elements-at-risk by using mainly free and easily accessible data. Both hazard and vulnerability assessments were compiled with GIS tools to draw comprehensive and tangible thematic risk maps

  17. Toward a comprehensive and realistic risk evaluation of engineered nanomaterials in the urban water system

    PubMed Central

    Duester, Lars; Burkhardt, Michael; Gutleb, Arno C.; Kaegi, Ralf; Macken, Ailbhe; Meermann, Björn; von der Kammer, Frank

    2014-01-01

    The European COoperation in Science and Technology (COST) Action ES1205 on the transfer of Engineered Nano materials from wastewater Treatment and stormwatEr to Rivers (ENTER) aims to create and to maintain a trans European network among scientists. This perspective article delivers a brief overview on the status quo at the beginning of the project by addressing the following aspects on engineered nano materials (ENMs) in the urban systems: (1) ENMs that need to be considered on a European level; (2) uncertainties on production-volume estimations; (3) fate of selected ENMs during waste water transport and treatment; (4) analytical strategies for ENM analysis; (5) ecotoxicity of ENMs, and (6) future needs. These six step stones deliver the derivation of the position of the ES1205 network at the beginning of the projects runtime, by defining six fundamental aspects that should be considered in future discussions on risk evaluation of ENMs in urban water systems. PMID:25003102

  18. 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.

  19. DYT1 dystonia increases risk taking in humans

    PubMed Central

    Arkadir, David; Radulescu, Angela; Raymond, Deborah; Lubarr, Naomi; Bressman, Susan B; Mazzoni, Pietro; Niv, Yael

    2016-01-01

    It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans. DOI: http://dx.doi.org/10.7554/eLife.14155.001 PMID:27249418

  20. Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

    PubMed Central

    Pineda, Silvia; Milne, Roger L.; Calle, M. Luz; Rothman, Nathaniel; López de Maturana, Evangelina; Herranz, Jesús; Kogevinas, Manolis; Chanock, Stephen J.; Tardón, Adonina; Márquez, Mirari; Guey, Lin T.; García-Closas, Montserrat; Lloreta, Josep; Baum, Erin; González-Neira, Anna; Carrato, Alfredo; Navarro, Arcadi; Silverman, Debra T.; Real, Francisco X.; Malats, Núria

    2014-01-01

    Introduction Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies. PMID:24818791

  1. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn

    2016-01-01

    Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111

  2. Porphyrin Metabolisms in Human Skin Commensal Propionibacterium acnes Bacteria: Potential Application to Monitor Human Radiation Risk

    PubMed Central

    Shu, M.; Kuo, S.; Wang, Y.; Jiang, Y.; Liu, Y.-T.; Gallo, R.L.; Huang, C.-M.

    2013-01-01

    Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin. Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood’s lamp. In this review, we compare the porphyrin biosynthesis in humans and P. acnes. Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation. The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases. Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk. PMID:23231351

  3. 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.

  4. 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.

  5. 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. PMID:22494384

  6. 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.

  7. 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.

  8. 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. PMID:18089548

  9. 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. PMID:24047742

  10. Approaches to characterizing human health risks of exposure to fibers.

    PubMed Central

    Vu, V T; Lai, D Y

    1997-01-01

    Naturally occurring and man-made (synthetic) fibers of respirable sizes are substances that have been identified by the U.S. Environmental Protection Agency (U.S. EPA) as priority substances for risk reduction and pollution prevention under the Toxic Substances Control Act (TSCA). The health concern for respirable fibers is based on the link of occupational asbestos exposure and environmental erionite fiber exposure to the development of chronic respiratory diseases, including interstitial lung fibrosis, lung cancer, and mesothelioma in humans. There is also considerable laboratory evidence indicating that a variety of fibers of varying physical and chemical characteristics can elicit fibrogenic and carcinogenic effects in animals under certain exposure conditions. This paper discusses key scientific issues and major default assumptions and uncertainties pertaining to the risk assessment of inhaled fibers. This is followed by a description of the types of assessment performed by the U.S. EPA to support risk management actions of new fibers and existing fibers under TSCA. The scope and depth of these risk assessments, however, vary greatly depending on whether the substance under review is an existing or a new fiber, the purpose of the assessment, the availability of data, time, and resources, and the intended nature of regulatory action. In general, these risk assessments are of considerable uncertainty because health hazard and human exposure information is often incomplete for most fibers. Furthermore, how fibers cause diseases and what specific determinants are critical to fiber-induced toxicity and carcinogenicity are still not completely understood. Further research to improve our knowledge base in fiber toxicology and additional toxicity and exposure data gathering are needed to more accurately characterize the health risks of inhaled fibers. PMID:9400747

  11. Biological surveys for ecological and human health risk assessments

    SciTech Connect

    Kathman, R.D.; Reagan, D.P.; Mayfield, J.C.

    1994-12-31

    In the past, human risk assessment was used almost exclusively to determine remedial measures at contaminated waste sites. Recently, however, ecological risk assessments have gained importance in evaluating risk not only to plants and animals, but also to humans through use of measures such as action levels of chemicals in fish tissue. Biological surveys were initiated to assess the mercury concentrations in finfish and shellfish in Lavaca Bay, Texas, part of which has been closed to fish and shellfish consumption since 1988 due to high levels of mercury in these organisms. Samples of particulate organic matter, cordgrass, invertebrates and fish were collected and analyzed for mercury concentrations. In conjunction with the biological surveys, an extensive sediment sampling program was conducted to map mercury concentrations in the sediment throughout the bay. A food web pathways model developed by personnel at National Marine Fisheries Service to assess mercury uptake by aquatic organisms in the bay has enabled the authors to concentrate on specific locations/habitats where mercury concentrations in sediment exceed a critical value. Biological data, along with stable isotope analyses, were used to validate the food web model. The conclusion is that mercury is continuing to enter the food web through the sediment-based food chain and not through the water column. These studies will be used to identify areas which need to be addressed for possible remedial measures, resulting in less uptake and bioaccumulation of mercury, and possible future removal of the fishing ban, thus establishing a direct linkage with human health concerns.

  12. No fear no risk! Human risk behavior is affected by chemosensory anxiety signals.

    PubMed

    Haegler, Katrin; Zernecke, Rebekka; Kleemann, Anna Maria; Albrecht, Jessica; Pollatos, Olga; Brückmann, Hartmut; Wiesmann, Martin

    2010-11-01

    An important aspect of cognitive functioning is decision-making, which depends on the correct interpretation of emotional processes. High trait anxiety has been associated with increased risk taking behavior in decision-making tasks. An interesting fact is that anxiety and anxiety-related chemosignals as well as decision-making share similar regions of neuronal activation. In order to ascertain if chemosensory anxiety signals have similar effects on risk taking behavior of healthy participants as high trait anxiety we used a novel computerized decision-making task, called Haegler's Risk Game (HRG). This task measures risk taking behavior based on contingencies and can be played repeatedly without a learning effect. To obtain chemosensory signals the sweat of 21 male donors was collected in a high rope course (anxiety condition). For the chemosensory control condition sweat was collected during an ergometer workout (exercise condition). In a double-blind study, 30 healthy recipients (16 females) had to play HRG while being exposed to sweat samples or empty control samples (control condition) in three sessions of randomized order. Comparison of the risk taking behavior of the three conditions showed significantly higher risk taking behavior in participants for the most risky choices during the anxiety condition compared to the control conditions. Additionally, recipients showed significantly higher latency before making their decision in the most risky choices during the anxiety condition. This experiment gives evidence that chemosensory anxiety signals are communicated between humans thereby increasing participants' risk taking behavior. PMID:20875438

  13. Good Ideas and Engagement Aren't Enough: School District Central Offices and the Micro-Politics of Implementing Comprehensive Human Resource Reform

    ERIC Educational Resources Information Center

    DeArmond, Michael

    2013-01-01

    This dissertation is about how organizational politics--or what some scholars call micro-politics--shapes the implementation of comprehensive human resource (HR) reform in school district central offices. Over the last decade, education reformers and advocates have promoted comprehensive HR reform as a way to improve teaching and learning in K-12…

  14. 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.

  15. 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.

  16. Aflatoxins as risk factors for hepatocellular carcinoma in humans.

    PubMed

    Wogan, G N

    1992-04-01

    On a global basis, primary liver cancer (PLC) is a very prevalent form of cancer. Wide variation of PLC incidence in different areas of the world suggests the involvement of environmental factors in its etiology. Two major classes of risk factors have been identified. Extensive evidence indicates the importance of infection by the hepatitis B virus as a major risk factor for PLC. Because many organic chemicals induce liver cancer in experimental animals, those to which human exposure is known to occur are also of interest with respect to their possible involvement as risk factors for PLC. Particular emphasis has been placed on aflatoxins because of the frequency with which they occur as food contaminants, together with their potency as liver carcinogens for a large number of experimental animals, including subhuman primates. Other mycotoxins, notably sterigmatocystin and fumonisin, also are relatively potent carcinogens for the liver of animals, but little is known about human exposure to them. Epidemiological surveys carried out over the past 25 years in Asia and Africa have revealed a strong statistical association between aflatoxin ingestion and PLC incidence. The combined experimental and epidemiological evidence has led to designation of aflatoxins as human carcinogens according to International Agency for Cancer Research criteria. Collectively, current evidence strongly suggests that PLC is of multifactorial origin, with probable interactions between viral and chemical agents in populations concurrently exposed to both classes of risk factors. Recently developed methods that permit individual monitoring of aflatoxin exposure, hepatitis B virus infection, and genetic damage caused by these agents are being applied in the design of molecular and biochemical epidemiological studies of the etiology of the disease. Application of this methodology may contribute to elucidation of the relative importance of interacting etiological agents in different populations

  17. 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...

  18. 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...

  19. 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…

  20. The human relevant potency threshold: reducing uncertainty by human calibration of cumulative risk assessments.

    PubMed

    Borgert, C J; Sargent, E V; Casella, G; Dietrich, D R; McCarty, L S; Golden, R J

    2012-03-01

    The 2008 National Research Council report "Phthalates and Cumulative Risk Assessment: Tasks Ahead," rejected the underlying premises of TEQ-like approaches - e.g., chemicals are true congeners; are metabolized and detoxified similarly; produce the same biological effects by the same mode of action; exhibit parallel dose response curves - instead asserting that cumulative risk assessment should apply dose addition (DA) to all chemicals that produce "common adverse outcomes" (CAOS). Published mixtures data and a human health risk assessment for phthalates and anti-androgens were evaluated to determine how firmly the DA-CAOS concept is supported and with what level of statistical certainty the results may be extrapolated to lower doses in humans. Underlying assumptions of the DA-CAOS concept were tested for accuracy and consistency against data for two human pharmaceuticals and its logical predictions were compared to human clinical and epidemiological experience. Those analyses revealed that DA-CAOS is scientifically untenable. Therefore, an alternative approach was developed - the Human-Relevant Potency-Threshold (HRPT) - that appears to fit the data better and avoids the contradictions inherent in the DA-CAOS concept. The proposed approach recommends application of independent action for phthalates and other chemicals with potential anti-androgenic properties at current human exposure levels. PMID:22057094

  1. Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01.

    PubMed

    Parham, L R; Briley, L P; Li, L; Shen, J; Newcombe, P J; King, K S; Slater, A J; Dilthey, A; Iqbal, Z; McVean, G; Cox, C J; Nelson, M R; Spraggs, C F

    2016-04-01

    Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other hypersensitivities represents an important first step in understanding the mechanism of these events. PMID:25987243

  2. Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01

    PubMed Central

    Parham, L R; Briley, L P; Li, L; Shen, J; Newcombe, P J; King, K S; Slater, A J; Dilthey, A; Iqbal, Z; McVean, G; Cox, C J; Nelson, M R; Spraggs, C F

    2016-01-01

    Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other hypersensitivities represents an important first step in understanding the mechanism of these events. PMID:25987243

  3. 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

  4. Comprehensive outcomes of on- and off-antiviral prophylaxis in hepatitis B patients undergoing cancer chemotherapy: A competing risks analysis.

    PubMed

    An, Jihyun; Shim, Ju Hyun; Kim, Seon-Ok; Choi, Jonggi; Kim, Sang-We; Lee, Danbi; Kim, Kang Mo; Lim, Young-Suk; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang; Suh, Dong Jin

    2016-09-01

    Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc. PMID:26945543

  5. Toxicity and human health risk of hair dyes.

    PubMed

    Nohynek, Gerhard J; Fautz, Rolf; Benech-Kieffer, Florence; Toutain, Herve

    2004-04-01

    Hair dyes and their ingredients have moderate to low acute toxicity. Human poisoning accidents are rare and have only been reported following oral ingestion. Contact sensitisation to hair dyes has been a safety issue, mainly as a consequence of unprotected professional exposure. Although the use of hair dyes has dramatically increased in industrialised countries during the last decades, the prevalence of sensitisation to hair dyes in the general and professional populations has stabilised or declined. In vitro genotoxicity tests on hair dye ingredients frequently had positive results, although their correlation with in vivo carcinogenicity for the chemical class of oxidative hair dye ingredients (aromatic amines) is uncertain. Positive in vivo genotoxicity results on hair dyes are rare. Studies in man found no evidence of genotoxic effects of hair dyes or their ingredients. On the basis of mechanistic studies, some in vivo positive hair dye ingredients (p-aminophenol, Lawsone) have been shown to pose no or negligible risk to human health. Although a recent case-control epidemiology study suggested an association of hair dye use and bladder cancer, a number of other studies, including prospective investigations on large populations, found no or negative correlations for bladder or other cancers. Although in vivo topical carcinogenicity studies on hair dye ingredients or commercial formulations yielded no evidence for systemic toxicity or carcinogenicity, oral carcinogenicity studies on hair dye ingredients at oral doses up to the maximum tolerated dose (MTD) suggested that some ingredients are carcinogenic in rodents. Human systemic exposure to various (14)C-labelled oxidative hair dyes under conditions of use was below 1.0% of the amount applied. Conservative risk assessments suggested no or negligible cancer risk, including for ingredients that were found to be positive in oral carcinogenicity studies. The results of reproductive toxicity studies and

  6. 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.

  7. 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

  8. 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. PMID:25223944

  9. 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

  10. 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…

  11. Implementing a framework for integrating toxicokinetics into human health risk assessment for agrochemicals.

    PubMed

    Terry, Claire; Hays, Sean; McCoy, Alene T; McFadden, Lisa G; Aggarwal, Manoj; Rasoulpour, Reza J; Juberg, Daland R

    2016-03-01

    A strategic and comprehensive program in which toxicokinetic (TK) measurements are made for all agrochemicals undergoing toxicity testing (both new compounds and compounds already registered for use) is described. This approach provides the data to more accurately assess the toxicokinetics of agrochemicals and their metabolites in laboratory animals and humans. Having this knowledge provides the ability to conduct more insightful toxicity studies, refine and interpret exposure assessments and reduce uncertainty in risk assessments. By developing a better understanding of TK across species, including humans via in vitro metabolism studies, any differences across species in TK can be identified early and the most relevant species can be selected for toxicity tests. It also provides the ability to identify any non-linearities in TK as a function of dose, which in turn can be used to identify a kinetically derived maximum dose (KMD) and avoid dosing inappropriately outside of the kinetic linear range. Measuring TK in key life stages also helps to identify changes in ADME parameters from in utero to adults. A robust TK database can also be used to set internal concentration based "Reference Concentrations" and Biomonitoring Equivalents (BE), and support selection of Chemical Specific Adjustment Factors (CSAF). All of these factors support the reduction of uncertainty throughout the entire risk assessment process. This paper outlines how a TK research strategy can be integrated into new agrochemical toxicity testing programs, together with a proposed Framework for future use. PMID:26472101

  12. 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

  13. 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

  14. Prophylaxis against hepatitis E: at risk populations and human vaccines.

    PubMed

    Wang, Xin; Li, Min; Li, Shaowei; Wu, Ting; Zhang, Jun; Xia, Ningshao; Zhao, Qinjian

    2016-07-01

    Hepatitis E is an emerging global disease caused by hepatitis E virus (HEV) infection. While in developing countries the infection was primarily due to poor sanitary conditions through intake of contaminated water or undercooked meats of infected animals, increasing cases of chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end-stage liver disease have been reported in organ transplant patients or in immune compromised patients in developed countries. Fortunately, hepatitis E is now a vaccine preventable disease with a HEV239 based vaccine licensed for human use. Much work is needed to enable its use outside China. This review recounted the development process of the vaccine, outlined the critical quality attributes of the vaccine antigen and, most importantly, listed the populations at risk for HEV infection and the subsequent disease. These at risk populations could benefit the most from the vaccination if the vaccine is widely adopted. PMID:26775537

  15. 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. PMID:23516823

  16. Human health risk associated with brominated flame-retardants (BFRs).

    PubMed

    Lyche, Jan L; Rosseland, Carola; Berge, Gunnar; Polder, Anuschka

    2015-01-01

    The purposes of this review are to assess the human exposure and human and experimental evidence for adverse effects of brominated flame-retardants (BFRs) with specific focus on intake from seafood. The leakage of BFRs from consumer products leads to exposure of humans from fetal life to adulthood. Fish and fish products contain the highest levels of BFRs and dominate the dietary intake of frequent fish eaters in Europe, while meat, followed by seafood and dairy products accounted for the highest US dietary intake. House dust is also reported as an important source of exposure for children as well as adults. The levels of BFRs in the general North American populations are higher than those in Europe and Japan and the highest levels are detected in infants and toddlers. The daily intake via breast milk exceeds the RfD in 10% of US infants. BFRs including PBDEs, HBCDs and TBBP-A have induced endocrine-, reproductive- and behavior effects in laboratory animals. Furthermore, recent human epidemiological data demonstrated association between exposure to BFRs and similar adverse effects as observed in animal studies. Fish including farmed fish and crude fish oil for human consumption may contain substantial levels of BFRs and infants and toddlers consuming these products on a daily basis may exceed the tolerable daily intake suggesting that fish and fish oil alone represent a risk to human health. This intake comes in addition to exposure from other sources (breast milk, other food, house dust). Because potential harmful concentrations of BFRs and other toxicants occur in fish and fish products, research on a wider range of products is warranted, to assess health hazard related to the contamination of fish and fish products for human consumption. PMID:25454234

  17. A comprehensive assessment of the risk of bone morphogenetic protein use in spinal fusion surgery and postoperative cancer diagnosis.

    PubMed

    Cahill, Kevin S; McCormick, Paul C; Levi, Allan D

    2015-07-01

    The risk of postoperative cancer following the use of recombinant human bone morphogenetic protein (BMP)-2 in spinal fusion is one potential complication that has received significant interest. Until recently, there has been little clinical evidence to support the assertion of potential cancer induction after BMP use in spinal surgery. This report aims to summarize the findings from clinical data available to date from the Yale University Open Data Access (YODA) project as well as more recently published large database studies regarding the association of BMP use in spinal fusion and the risk of postoperative cancer. A detailed review was based on online databases, primary studies, FDA reports, and bibliographies of key articles for studies that assessed the efficacy and safety of BMP in spinal fusion. In an analysis of the YODA project, one meta-analysis detected a statistically significant increase in cancer occurrence at 24 months but not at 48 months, and the other meta-analysis did not detect a significant increase in postoperative cancer occurrence. Analysis of 3 large health care data sets (Medicare, MarketScan, and PearlDiver) revealed that none were able to detect a significant increase in risk of malignant cancers when BMP was used compared with controls. The potential risk of postoperative cancer formation following the use of BMP in spinal fusion must be interpreted on an individual basis for each patient by the surgeon. There is no conclusive evidence that application of the common formulations of BMP during spinal surgery results in the formation of cancer locally or at a distant site. PMID:25860517

  18. Polymorphisms of human N-acetyltransferases and cancer risk.

    PubMed

    Agúndez, José A G

    2008-07-01

    Human arylamine N-acetyltransferases (CoASAc; NAT, EC 2.3.1.5) NAT1 and NAT2 play a key role in the metabolism of drugs and environmental chemicals and in the metabolic activation and detoxification of procarcinogens. Phenotyping analyses have revealed an association between NAT enzyme activities and the risk of developing several forms of cancer. As genotyping procedures have become available for NAT1 and NAT2 gene variations, hundreds of association studies on NAT polymorphisms and cancer risk have been conducted. Here we review the findings obtained from these studies. Evidence for a putative association of NAT1 polymorphism and myeloma, lung and bladder cancer, as well as association of NAT2 polymorphisms with non-Hodgkin lymphoma, liver, colorectal and bladder cancer have been reported. In contrast, no consistent evidence for a relevant association of NAT polymorphisms with brain, head & neck, breast, gastric, pancreatic or prostate cancer have been described. Although preliminary data are available, further well-powered studies are required to fully elucidate the role of NAT1 in most human cancers, and that of NAT2 in astrocytoma, meningioma, esophageal, renal, cervical and testicular cancers, as well as in leukaemia and myeloma. This review discusses controversial findings on cancer risk and putative causes of heterogeneity in the proposed associations, and it identifies topics that require further investigation, particularly mechanisms underlying association of NAT polymorphisms and risk for subsets of cancer patients with specific exposures, putative epistatic contribution of polymorphism for other xenobiotic-metabolising enzymes such as glutathione S-transferases of Cytochrome P450 enzymes, and genetic plus environmental interaction. PMID:18680472

  19. Variance After-Effects Distort Risk Perception in Humans.

    PubMed

    Payzan-LeNestour, Elise; Balleine, Bernard W; Berrada, Tony; Pearson, Joel

    2016-06-01

    In many contexts, decision-making requires an accurate representation of outcome variance-otherwise known as "risk" in economics. Conventional economic theory assumes this representation to be perfect, thereby focusing on risk preferences rather than risk perception per se [1-3] (but see [4]). However, humans often misrepresent their physical environment. Perhaps the most striking of such misrepresentations are the many well-known sensory after-effects, which most commonly involve visual properties, such as color, contrast, size, and motion. For example, viewing downward motion of a waterfall induces the anomalous biased experience of upward motion during subsequent viewing of static rocks to the side [5]. Given that after-effects are pervasive, occurring across a wide range of time horizons [6] and stimulus dimensions (including properties such as face perception [7, 8], gender [9], and numerosity [10]), and that some evidence exists that neurons show adaptation to variance in the sole visual feature of motion [11], we were interested in assessing whether after-effects distort variance perception in humans. We found that perceived variance is decreased after prolonged exposure to high variance and increased after exposure to low variance within a number of different visual representations of variance. We demonstrate these after-effects occur across very different visual representations of variance, suggesting that these effects are not sensory, but operate at a high (cognitive) level of information processing. These results suggest, therefore, that variance constitutes an independent cognitive property and that prolonged exposure to extreme variance distorts risk perception-a fundamental challenge for economic theory and practice. PMID:27161500

  20. 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

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

    PubMed

    Karyala, Prashanthi; Metri, Rahul; Bathula, Christopher; Yelamanchi, Syam K; Sahoo, Lipika; Arjunan, Selvam; Sastri, Narayan P; Chandra, Nagasuma

    2016-09-01

    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

  2. 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. PMID:25110548

  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. PMID:24769343

  4. MalaCards: A Comprehensive Automatically-Mined Database of Human Diseases.

    PubMed

    Rappaport, Noa; Twik, Michal; Nativ, Noam; Stelzer, Gil; Bahir, Iris; Stein, Tsippi Iny; Safran, Marilyn; Lancet, Doron

    2014-01-01

    Systems medicine provides insights into mechanisms of human diseases, and expedites the development of better diagnostics and drugs. To facilitate such strategies, we initiated MalaCards, a compendium of human diseases and their annotations, integrating and often remodeling information from 64 data sources. MalaCards employs, among others, the proven automatic data-mining strategies established in the construction of GeneCards, our widely used compendium of human genes. The development of MalaCards poses many algorithmic challenges, such as disease name unification, integrated classification, gene-disease association, and disease-targeted expression analysis. MalaCards displays a Web card for each of >19,000 human diseases, with 17 sections, including textual summaries, related diseases, related genes, genetic variations and tests, and relevant publications. Also included are a powerful search engine and a variety of categorized disease lists. This unit describes two basic protocols to search and browse MalaCards effectively. PMID:25199789

  5. Advancing human health risk assessment: integrating recent advisory committee recommendations.

    PubMed

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

    2013-07-01

    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

  6. 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

  7. 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.

  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. 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

  10. Mammalian toxicology overview and human risk assessment for sulfosulfuron.

    PubMed

    Healy, Charles E; Heydens, William F; Naylor, Mark W

    2004-06-01

    Sulfosulfuron is a low-use rate sulfonylurea herbicide. A review of the toxicity database for sulfosulfuron indicates that the molecule has a low order of acute toxicity. It is not genotoxic and is not a reproductive, developmental, or nervous system toxicant. There were no indications of endocrine disruption in any study performed with the molecule. The only findings considered to be an adverse effect in mammalian laboratory animals following prolonged subchronic or chronic exposure to sulfosulfuron were isolated to the urinary tract. These findings occurred in conjunction with findings of urolith formation following high-level chemical dosing, resulting in epithelial hyperplasia that, in a few cases, progressed to tumor formation. Mode-of-action information supports the conclusion that these tumors result from a non-genotoxic, threshold-based process that is well established and widely considered to be not relevant to humans. Based on its short-term, infrequent application pattern and very low use rate and crop residues, aggregate and cumulative risk assessments indicate that sulfosulfuron has substantial margins of exposure and does not represent a significant risk to human health. PMID:15135210

  11. 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. PMID:26006052

  12. Statistical analyses in trials for the comprehensive understanding of organogenesis and histogenesis in humans and mice.

    PubMed

    Otani, Hiroki; Udagawa, Jun; Naito, Kanta

    2016-06-01

    Statistical analyses based on the quantitative data from real multicellular organisms are useful as inductive-type studies to analyse complex morphogenetic events in addition to deductive-type analyses using mathematical models. Here, we introduce several of our trials for the statistical analysis of organogenesis and histogenesis of human and mouse embryos and foetuses. Multidimensional scaling has been applied to prove the existence and examine the mode of interkinetic nuclear migration, a regulatory mechanism of stem cell proliferation/differentiation in epithelial tubular tissues. Several statistical methods were used on morphometric data from human foetuses to establish the multidimensional standard growth curve and to describe the relation among the developing organs and body parts. Although the results are still limited, we show that these analyses are not only useful to understand the normal and abnormal morphogenesis in humans and mice but also to provide clues that could correlate aspects of prenatal developmental events with postnatal diseases. PMID:26935132

  13. External Validation of the Number of Risk Factors Score in a Palliative Care Outpatient Clinic at a Comprehensive Cancer Center

    PubMed Central

    Shariff, Imran; Thaler, Howard T.

    2014-01-01

    Abstract Background: Prognostic tools are available to predict if terminally ill cancer patients have days or weeks to live. Tools for predicting the prognosis in ambulatory patients at an earlier stage are lacking. The Number of Risk Factors (NRF) score developed in ambulatory cancer patients receiving palliative radiation therapy may be suitable for this purpose but has not been tested in a palliative care setting. Objective: Our aim was to evaluate the prognostic accuracy of the NRF score in patients referred to a palliative care outpatient clinic at a comprehensive cancer center. Methods: We conducted a retrospective chart review of NRF scores and survival in 300 consecutive, newly referred patients. Measurements included primary cancer type, extent of disease, Karnofsky Performance Scale (KPS) score, and survival duration after first visit. One point was allocated each for cancer other than breast cancer, metastases other than bone, and low KPS score. Results: Of 300 patients, 236 (79%) had advanced disease. Of those 236, 212 (90%) had a cancer other than breast cancer, 180 (76%) had metastatic disease in sites other than bone, and 64 (27%) had a KPS score <70%. During the 2-year follow-up, 221 (94%) patients died, with overall median survival of 4.9 months (95% confidence interval, 3.9–6.1 months). NRF scores of 0 to 1, 2, and 3 split the sample into subgroups with highly significantly different survival among the groups, with medians 9.0, 4.6, and 2.1 months, respectively (Wilcoxon test χ2=43.9, degrees of freedom [df] 2, p<0.0001). A simple parametric model was fit to determine the probability of subgroup members surviving to a certain number of months. Conclusions: In cancer patients referred to palliative care earlier in their disease trajectory, the NRF score may be a useful prognostic tool. Further validation in other palliative care populations is needed. PMID:24871990

  14. 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

  15. Could human cold adaptation decrease the risk of cardiovascular disease?

    PubMed

    Kralova Lesna, I; Rychlikova, J; Vavrova, L; Vybiral, S

    2015-08-01

    The impact of repeated exposure to cold and cold adaptation on human cardiovascular health is not fully understood. The aim of the study was to determine the effect of cold adaptation on cardiovascular risk factors, thyroid hormones and the capacity of humans to reset the damaging effect of oxidative stress. Ten well cold-adapted winter swimmers (CA) and 16 non-adapted controls (CON) were enroled in this experiment to test whether cold adaptation could influence the parameters of lipoprotein metabolism, cholesterol efflux capacity (CEC), homocysteine, thyroid hormones, antioxidant defence markers (reduced glutathione (GSH), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), catalase (CAT) and paraoxonase 1 (PON1)) and oxidative stress markers (concentration of conjugated dienes (CD)). A decreased apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio was found in the CA group (p<0.05), but other lipoprotein parameters, including CEC, did not differ significantly. Plasma homocysteine was lower in CA subjects in comparison with controls (p<0.05). Higher triiodothyronine (T3) values were observed in the CA compared to the CON (p<0.05) group, but TSH and other thyroid hormones did not differ between both groups. CA subjects had lower activity of GPX1 (p<0.05), lower concentrations of CD (p<0.05) and increased activities of PON1 (p<0.001) compared to CON subjects. A trend for decreased activity of CAT (p=0.06) in CA compared to CON groups was also observed, but GSH levels did not differ significantly. Zn concentration was higher in the CA group than in the CON group (p<0.001). Human cold adaptation can influence oxidative stress markers. Trends towards the improvement of cardiovascular risk factors in cold-adapted subjects also indicate the positive effect of cold adaptation on cardio-protective mechanisms. PMID:26267514

  16. Human Insulin Does Not Increase Bladder Cancer Risk

    PubMed Central

    Tseng, Chin-Hsiao

    2014-01-01

    Background Whether human insulin can induce bladder cancer is rarely studied. Methods The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression. Results There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. Conclusions This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication. PMID:24466131

  17. 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

  18. Comprehensive human urine standards for comparability and standardization in clinical proteome analysis

    PubMed Central

    Mischak, Harald; Kolch, Walter; Aivaliotis, Michalis; Bouyssié, David; Court, Magali; Dihazi, Hassan; Dihazi, Gry H.; Franke, Julia; Garin, Jérôme; Gonzalez de Peredo, Anne; Iphöfer, Alexander; Jänsch, Lothar; Lacroix, Chrystelle; Makridakis, Manousos; Masselon, Christophe; Metzger, Jochen; Monsarrat, Bernard; Mrug, Michal; Norling, Martin; Novak, Jan; Pich, Andreas; Pitt, Andrew; Bongcam-Rudloff, Erik; Siwy, Justyna; Suzuki, Hitoshi; Thongboonkerd, Visith; Wang, Li-Shun; Zoidakis, Jérôme; Zürbig, Petra; Schanstra, Joost P.; Vlahou, Antonia

    2011-01-01

    Purpose Urine proteomics is emerging as a powerful tool for biomarker discovery. The purpose of this study is the development of a well characterized “real life” sample that can be used as reference standard in urine clinical proteomics studies. Experimental design We report on the generation of male and female urine samples that are extensively characterized by different platforms and methods (CE-MS, LC-MS, LC-MS/MS, GeLC-MS, and 2DE-MS) for their proteome and peptidome. In several cases analysis involved a definition of the actual biochemical entities, i.e. proteins/peptides associated with molecular mass and detected posttranslational modifications and the relative abundance of these compounds. Results The combination of different technologies allowed coverage of a wide mass range revealing the advantages and complementarities of the different technologies. Application of these samples in “inter-laboratory” and “inter-platform” data comparison is also demonstrated. Conclusions and Clinical Relevance These well characterized urine samples are freely available upon request to enable data comparison especially in the context of biomarker discovery and validation studies. It is also expected that they will provide the basis for the comprehensive characterization of the urinary proteome. PMID:21137064

  19. Epithelial-mesenchymal transition in human cancer: comprehensive reprogramming of metabolism, epigenetics, and differentiation.

    PubMed

    Li, Linna; Li, Wenliang

    2015-06-01

    The epithelial-mesenchymal transition (EMT) is a developmental process that is important for embryogenesis, wound healing, organ fibrosis, and cancer metastasis. Cancer-associated EMT is not a simple process to acquire migration and invasion ability, but a complicated and comprehensive reprogramming, involved in metabolism, epigenetics and differentiation, through which differentiated epithelial cancer cells reverse to an undifferentiated state, not only expressing stem cell markers, but also acquiring stem cell-like functions. Here we review recent ideas and discoveries that illustrate the links among metabolism, epigenetics, and dedifferentiation during EMT, with special emphasis on the primary driving force and ultimate goal of cancer-associated EMT - of the energy and for the energy. Furthermore, we highlight on the specificity of epigenetic modification during EMT, with an aim to explain how the repression of epithelial genes and activation of mesenchymal genes are coordinated simultaneously through EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on epigenetic and metabolic levels, and discuss its potential for clinical application. PMID:25595324

  20. A comprehensive assessment of human exposure to phthalates from environmental media and food in Tianjin, China.

    PubMed

    Ji, Yaqin; Wang, Fumei; Zhang, Leibo; Shan, Chunyan; Bai, Zhipeng; Sun, Zengrong; Liu, Lingling; Shen, Boxiong

    2014-08-30

    A total of 448 samples including foodstuffs (rice, steamed bun, vegetables, meat, poultry, fish, milk and fruits), ambient PM10, drinking water, soil, indoor PM10 and indoor dust samples from Tianjin were obtained to determine the distribution of six priority phthalates (PAEs) and assess the human exposure to them. The results indicated that DBP and DEHP were the most frequently detected PAEs in these samples. The concentrations of PAEs in environmental media were higher than those in food. We estimated the daily intake (DI) of PAEs via ingestion, inhalation and dermal absorption from five sources (food, water, air, dust and soil). Dietary intake was the main exposure source to DEP, BBP, DEHP and DOP, whereas water ingestion/absorption was the major source of exposure to DBP, DEHP and DOP. Although food and water were the overwhelmingly predominant sources of PAEs intake by Tianjin population, contaminated air was another important source of DMP, DEP and DBP contributing to up to 45% of the exposure. The results of this study will help in understanding the major pathways of human exposure to PAEs. These findings also suggest that human exposure to phthalate esters via the environment should not be overlooked. PMID:25051237

  1. 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

    2016-01-01

    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

  2. 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

  3. 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

  4. 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

    2016-03-01

    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

  5. 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

  6. 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. PMID:19100684

  7. Comprehensive assembly of novel transcripts from unmapped human RNA-Seq data and their association with cancer.

    PubMed

    Kazemian, Majid; Ren, Min; Lin, Jian-Xin; Liao, Wei; Spolski, Rosanne; Leonard, Warren J

    2015-08-01

    Crucial parts of the genome including genes encoding microRNAs and noncoding RNAs went unnoticed for years, and even now, despite extensive annotation and assembly of the human genome, RNA-sequencing continues to yield millions of unmappable and thus uncharacterized reads. Here, we examined > 300 billion reads from 536 normal donors and 1,873 patients encompassing 21 cancer types, identified ~300 million such uncharacterized reads, and using a distinctive approach de novo assembled 2,550 novel human transcripts, which mainly represent long noncoding RNAs. Of these, 230 exhibited relatively specific expression or non-expression in certain cancer types, making them potential markers for those cancers, whereas 183 exhibited tissue specificity. Moreover, we used lentiviral-mediated expression of three selected transcripts that had higher expression in normal than in cancer patients and found that each inhibited the growth of HepG2 cells. Our analysis provides a comprehensive and unbiased resource of unmapped human transcripts and reveals their associations with specific cancers, providing potentially important new genes for therapeutic targeting. PMID:26253570

  8. Comprehensive assembly of novel transcripts from unmapped human RNA-Seq data and their association with cancer

    PubMed Central

    Kazemian, Majid; Ren, Min; Lin, Jian-Xin; Liao, Wei; Spolski, Rosanne; Leonard, Warren J

    2015-01-01

    Crucial parts of the genome including genes encoding microRNAs and noncoding RNAs went unnoticed for years, and even now, despite extensive annotation and assembly of the human genome, RNA-sequencing continues to yield millions of unmappable and thus uncharacterized reads. Here, we examined > 300 billion reads from 536 normal donors and 1,873 patients encompassing 21 cancer types, identified ∼300 million such uncharacterized reads, and using a distinctive approach de novo assembled 2,550 novel human transcripts, which mainly represent long noncoding RNAs. Of these, 230 exhibited relatively specific expression or non-expression in certain cancer types, making them potential markers for those cancers, whereas 183 exhibited tissue specificity. Moreover, we used lentiviral-mediated expression of three selected transcripts that had higher expression in normal than in cancer patients and found that each inhibited the growth of HepG2 cells. Our analysis provides a comprehensive and unbiased resource of unmapped human transcripts and reveals their associations with specific cancers, providing potentially important new genes for therapeutic targeting. PMID:26253570

  9. 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...

  10. HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology

    PubMed Central

    Gille, Christoph; Bölling, Christian; Hoppe, Andreas; Bulik, Sascha; Hoffmann, Sabrina; Hübner, Katrin; Karlstädt, Anja; Ganeshan, Ramanan; König, Matthias; Rother, Kristian; Weidlich, Michael; Behre, Jörn; Holzhütter, Herrmann-Georg

    2010-01-01

    We present HepatoNet1, the first reconstruction of a comprehensive metabolic network of the human hepatocyte that is shown to accomplish a large canon of known metabolic liver functions. The network comprises 777 metabolites in six intracellular and two extracellular compartments and 2539 reactions, including 1466 transport reactions. It is based on the manual evaluation of >1500 original scientific research publications to warrant a high-quality evidence-based model. The final network is the result of an iterative process of data compilation and rigorous computational testing of network functionality by means of constraint-based modeling techniques. Taking the hepatic detoxification of ammonia as an example, we show how the availability of nutrients and oxygen may modulate the interplay of various metabolic pathways to allow an efficient response of the liver to perturbations of the homeostasis of blood compounds. PMID:20823849

  11. Comprehensive View of the Human Mating Process Among Young Couples in Isfahan-Iran: An Explanatory Mixed-Method Study

    PubMed Central

    Merghati Khoei, Effat; Ziaei, Tayebe; Salehi, Mehrdad; Farajzadegan, Ziba

    2013-01-01

    Background: Heterosexual relationship is the main component of mate selection. Regardless of the importance of mate favorites, little is known about exact valued criteria in potential mates. Objectives: This study was designed to comprehensively explain the theoretical view of the human mating process. Materials and Methods: This was as an explanatory mixed–method study. The first phase was a cross-sectional quantitative study with two Farsi-modified versions of instruments: preferences concerning potential mates and factors of choosing a mate; content analysis was the second phase. The quantitative phase of this study consisted of 202 dating couples, decided to get married. The qualitative phase consisted of 28 participants who acquired the extreme scores (highest and lowest) in the first phase. Results: Average age of marriage for women and men was 23.04 and 26.41 respectively; the actual age difference was 3.37 years (women younger than men). The results of this study in support of evolution-based theory explained that, age is a preference and choosing an older husband and a younger wife is due to having reproductive capacity. Also, they mentioned that appearance is necessary for men because of sexual attraction, not as a prediction for the next generation appearance. In both phases of this study, both genders had a strong emphasis on “chastity” in a potential mate. Results showed that, men preferred a mate who was a good housewife, capable of cooking, and women preferred a mate with “Good earning capacity”, “Good financial prospect” “university education”, “Favorable social status” and “Industriousness”. Conclusions: The results confirmed that for a comprehensive view in human mating process, we need a combined theoretical approach as well as qualitative and quantitative study to explore the real meaning of each preference in a mate. PMID:24693380

  12. 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. PMID:25714400

  13. 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. PMID:27215155

  14. Autofluorescence of normal and tumor mucosa of human colon: a comprehensive analysis

    NASA Astrophysics Data System (ADS)

    Bottiroli, Giovanni F.; Marchesini, Renato; Croce, Anna C.; Dal Fante, Marco; Cuzzoni, Carolina; Di Palma, Silvana; Spinelli, Pasquale

    1993-08-01

    Both 'in vivo' and 'ex vivo' spectrofluorometric studies of neoplastic and non-neoplastic mucosa of human colon have been carried out, in order to verify the potentials of tissue natural fluorescence as a possible parameter to distinguish normal from diseased tissues, Spectrofluorometric analysis performed at colonoscopy on patients affected by neoplasia, showed that adenocarcinoma, adenoma and non-neoplastic mucosa differ in the fluorescence emissions. The results have been interpreted according to the data obtained on cryostatic sections from biopsies by means of a microspectrofluorometric analysis carried out on each histological component.

  15. 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. PMID:26657358

  16. Electronic cigarettes: incorporating human factors engineering into risk assessments

    PubMed Central

    Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

    2014-01-01

    Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through January 2014 and publications relevant to HF were incorporated. Voluntary adverse event (AE) reports submitted to the US Food and Drug Administration (FDA) and the package labelling of 12 e-cigarette products were analysed. Results No studies specifically addressing the impact of HF on e-cigarette use risks were identified. Most e-cigarette users are smokers, but data on the user population are inconsistent. No articles focused specifically on e-cigarette use environments, storage conditions, product operational requirements, product complexities, user errors or misuse. Twelve published studies analysed e-cigarette labelling and concluded that labelling was inadequate or misleading. FDA labelling analysis revealed similar concerns described in the literature. AE reports related to design concerns are increasing and fatalities related to accidental exposure and misuse have occurred; however, no publications evaluating the relationship between AEs and HF were identified. Conclusions The HF impacting e-cigarette use and related hazards are inadequately characterised. Thorough analyses of user–product–environment interfaces, product complexities and AEs associated with typical and atypical use are needed to better incorporate HF engineering principles to inform and potentially reduce or mitigate the emerging hazards associated with e-cigarette products. PMID:24732164

  17. 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

  18. Comprehensive analysis and identification of the human STIM1 domains for structural and functional studies.

    PubMed

    How, Jonathan; Zhang, Ai; Phillips, Margaret; Reynaud, Aline; Lu, Si Yan; Pan, Lucy Xin; Ho, Hai Ting; Yau, Yin Hoe; Guskov, Albert; Pervushin, Konstantin; Shochat, Susana Geifman; Eshaghi, Said

    2013-01-01

    STIM1 is a Ca(2+) sensor within the ER membrane known to activate the plasma membrane store-operated Ca(2+) channel upon depletion of its target ion in the ER lumen. This activation is a crucial step to initiate the Ca(2+) signaling cascades within various cell types. Human STIM1 is a 77.4 kDa protein consisting of various domains that are involved in Ca(2+) sensing, oligomerization, and channel activation and deactivation. In this study, we identify the domains and boundaries in which functional and stable recombinant human STIM1 can be produced in large quantities. To achieve this goal, we cloned nearly 200 constructs that vary in their initial and terminal residues, length and presence of the transmembrane domain, and we conducted expression and purification analyses using these constructs. The results revealed that nearly half of the constructs could be expressed and purified with high quality, out of which 25% contained the integral membrane domain. Further analyses using surface plasmon resonance, nuclear magnetic resonance and a thermostability assay verified the functionality and integrity of these constructs. Thus, we have been able to identify the most stable and well-behaved domains of the hSTIM1 protein, which can be used for future in vitro biochemical and biophysical studies. PMID:23320111

  19. 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

  20. EpiFactors: a comprehensive database of human epigenetic factors and complexes

    PubMed Central

    Medvedeva, Yulia A.; Lennartsson, Andreas; Ehsani, Rezvan; Kulakovskiy, Ivan V.; Vorontsov, Ilya E.; Panahandeh, Pouda; Khimulya, Grigory; Kasukawa, Takeya; Drabløs, Finn

    2015-01-01

    Epigenetics refers to stable and long-term alterations of cellular traits that are not caused by changes in the DNA sequence per se. Rather, covalent modifications of DNA and histones affect gene expression and genome stability via proteins that recognize and act upon such modifications. Many enzymes that catalyse epigenetic modifications or are critical for enzymatic complexes have been discovered, and this is encouraging investigators to study the role of these proteins in diverse normal and pathological processes. Rapidly growing knowledge in the area has resulted in the need for a resource that compiles, organizes and presents curated information to the researchers in an easily accessible and user-friendly form. Here we present EpiFactors, a manually curated database providing information about epigenetic regulators, their complexes, targets and products. EpiFactors contains information on 815 proteins, including 95 histones and protamines. For 789 of these genes, we include expressions values across several samples, in particular a collection of 458 human primary cell samples (for approximately 200 cell types, in many cases from three individual donors), covering most mammalian cell steady states, 255 different cancer cell lines (representing approximately 150 cancer subtypes) and 134 human postmortem tissues. Expression values were obtained by the FANTOM5 consortium using Cap Analysis of Gene Expression technique. EpiFactors also contains information on 69 protein complexes that are involved in epigenetic regulation. The resource is practical for a wide range of users, including biologists, pharmacologists and clinicians. Database URL: http://epifactors.autosome.ru PMID:26153137

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

    PubMed

    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. PMID:26055097

  2. Considerations for Comprehensive Analyses of Sporozoite-Based Controlled Human Malaria Infection Studies

    PubMed Central

    Lover, Andrew A.

    2015-01-01

    There has been renewed interest in the use of sporozoite-based approaches for controlled human malaria infections (CHMIs), and several sets of human challenge studies have recently completed. A study undertaken in Tanzania and published in 2014 found dose dependence between 10,000 and 25,000 sporozoite doses, as well as divergent times-to-parasitemia relative to earlier studies in European volunteers, with important implications for planning future studies. Analysis of time-to-event data has had extensive development in recent years, but these methods have had limited exposure outside biostatistics. Expansion of the published analyses to include recent methodological approaches optimized for the types of data used could provide a richer analysis of these studies and may result in alternative findings. Specifically, in a re-analysis of these data using survival analysis techniques, the differences recorded in prepatent periods between the two dosing regimens do not reach statistical significance, and there is no evidence for statistically significant differences in prepatent periods between the Dutch and Tanzanian study sites. Although these findings do not impact the reported safety and tolerability of challange with cryopreserved Plasmodium falciparum sporozoites (PfSPZ), or invalidate the authors' hypotheses regarding naturally acquired immunity and its effect on parasite growth rates and prepatent periods, they highlight important opportunities to more fully use datasets from these trials and related CHMI experiments in the planning of future challenge studies. PMID:26392161

  3. Comprehensive Analysis of Maillard Protein Modifications in Human Lenses: Effect of Age and Cataract

    PubMed Central

    Smuda, Mareen; Henning, Christian; Raghavan, Cibin T.; Johar, Kaid; Vasavada, Abhay R.; Nagaraj, Ram H.; Glomb, Marcus A.

    2015-01-01

    In human lens proteins, advanced glycation endproducts (AGEs) originate from the reaction of glycating agents, e.g., vitamin C and glucose. AGEs have been considered to play a significant role in lens aging and cataract formation. Although several AGEs have been detected in the human lens, the contribution of individual glycating agents to their formation remains unclear. A highly sensitive liquid chromatography–tandem mass spectrometry multimethod was developed that allowed us to quantitate 21 protein modifications in normal and cataractous lenses, respectively. N6-Carboxymethyl lysine, N6-carboxyethyl lysine, N7-carboxyethyl arginine, methylglyoxal hydroimidazolone 1, and N6-lactoyl lysine were found to be the major Maillard protein modifications among these AGEs. The novel vitamin C specific amide AGEs, N6-xylonyl and N6-lyxonyl lysine, but also AGEs from glyoxal were detected, albeit in minor quantities. Among the 21 modifications, AGEs from the Amadori product (derived from the reaction of glucose and lysine) and methylglyoxal were dominant. PMID:25849437

  4. Risks associated with magnetic resonance imaging and cervical collar in comatose, blunt trauma patients with negative comprehensive cervical spine computed tomography and no apparent spinal deficit

    PubMed Central

    Dunham, C Michael; Brocker, Brian P; Collier, B David; Gemmel, David J

    2008-01-01

    Introduction In blunt trauma, comatose patients (Glasgow Coma Scale score 3 to 8) with a negative comprehensive cervical spine (CS) computed tomography assessment and no apparent spinal deficit, CS clearance strategies (magnetic resonance imaging [MRI] and prolonged cervical collar use) are controversial. Methods We conducted a literature review to delineate risks for coma, CS instability, prolonged cervical collar use, and CS MRI. Results Based on our search of the literature, the numbers of functional survivor patients among those who had sustained blunt trauma were as follows: 350 per 1,000 comatose unstable patients (increased intracranial pressure [ICP], hypotension, hypoxia, or early ventilator-associated pneumonia); 150 per 1,000 comatose high-risk patients (age > 45 years or Glasgow Coma Scale score 3 to 5); and 600 per 1,000 comatose stable patients (not unstable or high risk). Risk probabilities for adverse events among unstable, high-risk, and stable patients were as follows: 2.5% for CS instability; 26.2% for increased intensive care unit complications with prolonged cervical collar use; 9.3% to 14.6% for secondary brain injury with MRI transportation; and 20.6% for aspiration during MRI scanning (supine position). Additional risk probabilities for adverse events among unstable patients were as follows: 35.8% for increased ICP with cervical collar; and 72.1% for increased ICP during MRI scan (supine position). Conclusion Blunt trauma coma functional survivor (independent living) rates are alarming. When a comprehensive CS computed tomography evaluation is negative and there is no apparent spinal deficit, CS instability is unlikely (2.5%). Secondary brain injury from the cervical collar or MRI is more probable than CS instability and jeopardizes cerebral recovery. Brain injury severity, probability of CS instability, cervical collar risk, and MRI risk assessments are essential when deciding whether CS MRI is appropriate and for determining the timing of

  5. 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. PMID:26946252

  6. 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

  7. Risk Factors for Anogenital Human Papillomavirus Infection in Men

    PubMed Central

    Nielson, Carrie M.; Harris, Robin B.; Dunne, Eileen F.; Abrahamsen, Martha; Papenfuss, Mary R.; Flores, Roberto; Markowitz, Lauri E.; Giuliano, Anna R.

    2013-01-01

    Background Human papillomavirus (HPV) is strongly associated with cervical and other anogenital cancers. Identification of risk factors for HPV infection in men may improve our understanding of HPV transmission and prevention. Methods HPV testing for 37 types was conducted in 463 men 18–40 years old recruited from 2 US cities. The entire anogenital region and semen were sampled. A self-administered questionnaire was completed. Multivariate logistic regression aided the identification of independent risk factors for any HPV type, oncogenic HPV types, and nononcogenic HPV types. Results Prevalence was 65.4% for any HPV, 29.2% for oncogenic HPV, and 36.3% for nononcogenic HPV. Factors significantly associated with any HPV were smoking ≥10 cigarettes per day (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0–5.3]) and lifetime number of female sex partners (FSPs) (OR for ≥21, 2.5 [95% CI, 1.3–4.6]), and factors significantly associated with oncogenic HPV were lifetime number of FSPs (OR for ≥21, 7.4 [95% CI, 3.4–16.3]) and condom use during the past 3 months (OR for more than half the time, 0.5 [95% CI, 0.3–0.8]). For nononcogenic HPV, a significant association was found for number of FSPs during the past 3 months (OR for ≥2, 2.9 [95% CI, 1.4–6.3]). Conclusions Lifetime and recent number of FSPs, condom use, and smoking were modifiable risk factors associated with HPV infection in men. PMID:17955431

  8. 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.

  9. 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...

  10. 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...

  11. Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer

    PubMed Central

    Kozarewa, Iwanka; Fenwick, Kerry; Assiotis, Ioannis; Mitsopoulos, Costas; Sims, David; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J.; Ashworth, Alan

    2011-01-01

    Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function. PMID:21750719

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

    PubMed

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

    2016-01-01

    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. PMID:27532820

  13. Gaps in comprehension of ear development impede successful human hearing organ restoration

    PubMed Central

    Jahan, Israt; Pan, Ning; Elliott, Karen L.; Fritzsch, Bernd

    2015-01-01

    Neurosensory hearing loss is a growing problem of super-aged societies. Cochlear implants can restore some hearing, but rebuilding a lost hearing organ would be superior. Research has discovered many cellular and molecular steps to develop a hearing organ but translating those insights into hearing organ restoration remains unclear. We cannot make various hair cell types and arrange them into their specific patterns surrounded by the right type of supporting cells in the right numbers. Our overview of the topologically highly organized and functionally diversified cellular mosaic of the mammalian hearing organ highlights what is known and unknown about its development. Following this analysis, we suggest critical steps to guide future attempts toward restoration of a functional OC. We argue that generating mutant mouse lines that mimic human pathology to fine-tune attempts toward long-term functional restoration are needed to go beyond the hope generated by restoring single hair cells. PMID:26208302

  14. [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. PMID:23223722

  15. A comprehensive assessment of human strivings: test-retest reliability and validity of the Reiss Profile.

    PubMed

    Havercamp, Susan M; Reiss, Steven

    2003-10-01

    Sensitivity theory provides an analysis of personality based on what people say motivates their behavior. After Reiss and Havercamp (1998) confirmed a 15-factor solution to self-reported human strivings, the Reiss Profile of Fundamental Goals and Motivation Sensitivities (Reiss & Havercamp, 1998) psychometric instrument was standardized. In 3 studies, the Reiss Profile was shown to possess good test-retest and internal reliability and concurrent and criterion validity. Ten independent samples of adults (n = 764) and a comparison group (n = 737) participated in these studies. Pearson product-moment correlations between the Marlowe-Crowne Social Desirability Scale (Crowne & Marlowe, 1960) and the Reiss Profile ranged in absolute value from .01 to.39 (M =.16). How people self-reported their trait motives correlated with how they behaved in the "real world." The Reiss Profile can be used to study motivational traits. PMID:12946919

  16. Human immunodeficiency virus-negative plasmablastic lymphoma: a comprehensive analysis of 114 cases.

    PubMed

    Liu, Min; Liu, Bailong; Liu, Bin; Wang, Qiang; Ding, Lijuan; Xia, Chengcheng; Dong, Lihua

    2015-04-01

    Human immunodeficiency virus-negative plasma-blastic lymphoma (PBL) is an extremely rare entity. Its clinicopathological features, optimal treatment strategy and prognostic factors remain obsure. An extensive search was performed in the English language literature within the Pubmed database using the key words: 'plasmablastic lymphoma and human immunodeficiency virus-negative or immunocompetent'. Data from 114 patients from 52 articles were analyzed. The mean patient age at diagnosis was 58.90 years (range, 2-86). HIV-negative PBL showed a predilection for elderly individuals (patients older than 60 years, 56.14%) and affected more males than females (M:F, 2.29:1). Ann Arbor stage IV patients accounted for 39.22% while bone marrow involvement was less frequent (12.79%). The Ki-67 index was high with a mean expression of 83%. Epstein-Barr virus (EBV) infection was common being positive in 58.70% of the patients while herpesvirus-8 (HHV-8) infection was rare being positive in only 7.55% of the patients. Immunosuppression was noted in 28.16% of patients. The median overall survival (OS) was 19 months. The 1- and 2-year survival rates were 52.3 and 45.3%, respectively. Age, gender and primary site showed no strong relationship with OS while Immunosuppression, Ann Arbor stage IV and EBV negativity were able to predict a poorer OS. Either complete remission (CR) or partial remission (PR) was superior to the refractory group in OS (P<0.0001 and P=0.0066, respectively). For stage Ⅰ patients, the application of radiotherapy did not improve the OS. In conclusion, HIV-negative PBL is a distinct entity likely occurring in elderly and immunosuppressed individuals. Immunosuppression status, Ann Arbor stage IV, EBV negativity and refractory to treatment are poor prognostic factors of OS in HIV-negative PBL. PMID:25695332

  17. Inflammatory bowel diseases and human reproduction: a comprehensive evidence-based review.

    PubMed

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

    2014-06-21

    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

  18. Comprehensive database of human E3 ubiquitin ligases: application to aquaporin-2 regulation.

    PubMed

    Medvar, Barbara; Raghuram, Viswanathan; Pisitkun, Trairak; Sarkar, Abhijit; Knepper, Mark A

    2016-07-01

    Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, "What E3 ubiquitin ligase is most likely to be responsible for AQP2 ubiquitination?" using large-scale data integration based on Bayes' rule. The first step was to bioinformatically identify all E3 ligase genes coded by the human genome. The 377 E3 ubiquitin ligases identified in the human genome, consisting predominant of HECT, RING, and U-box proteins, have been used to create a publically accessible and downloadable online database (https://hpcwebapps.cit.nih.gov/ESBL/Database/E3-ligases/). We also curated a second database of E3 ligase accessory proteins that included BTB domain proteins, cullins, SOCS-box proteins, and F-box proteins. Using Bayes' theorem to integrate information from multiple large-scale proteomic and transcriptomic datasets, we ranked these 377 E3 ligases with respect to their probability of interaction with AQP2. Application of Bayes' rule identified the E3 ligases most likely to interact with AQP2 as (in order of probability): NEDD4 and NEDD4L (tied for first), AMFR, STUB1, ITCH, ZFPL1. Significantly, the two E3 ligases tied for top rank have also been studied extensively in the reductionist literature as regulatory proteins in renal tubule epithelia. The concordance of conclusions from reductionist and systems-level data provides strong motivation for further studies of the roles of NEDD4 and NEDD4L in the regulation of AQP2 protein turnover. PMID:27199454

  19. Real-Time Reverse Transcription-PCR Assay for Comprehensive Detection of Human Rhinoviruses▿

    PubMed Central

    Lu, Xiaoyan; Holloway, Brian; Dare, Ryan K.; Kuypers, Jane; Yagi, Shigeo; Williams, John V.; Hall, Caroline B.; Erdman, Dean D.

    2008-01-01

    Human rhinoviruses (HRVs) are important contributors to respiratory disease, but their healthcare burden remains unclear, primarily because of the lack of sensitive, accurate, and convenient means of determining their causal role. To address this, we developed and clinically validated the sensitivity and specificity of a real-time reverse transcription-PCR (RT-PCR) assay targeting the viral 5′ noncoding region defined by sequences obtained from all 100 currently recognized HRV prototype strains and 85 recently circulating field isolates. The assay successfully amplified all HRVs tested and could reproducibly detect 50 HRV RNA transcript copies, with a dynamic range of over 7 logs. In contrast, a quantified RNA transcript of human enterovirus 68 (HEV68) that showed the greatest sequence homology to the HRV primers and probe set was not detected below a concentration of 5 × 105 copies per reaction. Nucleic acid extracts of 111 coded respiratory specimens that were culture positive for HRV or HEV were tested with the HRV real-time RT-PCR assay and by two independent laboratories that used different in-house HRV/HEV RT-PCR assays. Eighty-seven HRV-culture-positive specimens were correctly identified by the real-time RT-PCR assay, and 4 of the 24 HEV-positive samples were positive for HRV. HRV-specific sequences subsequently were identified in these four specimens, suggesting HRV/HEV coinfection in these patients. The assay was successfully applied in an investigation of a coincidental outbreak of HRV respiratory illness among laboratory staff. PMID:18057136

  20. 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.

  1. 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. PMID:18694755

  2. Human parechovirus and the risk of type 1 diabetes.

    PubMed

    Kolehmainen, P; Koskiniemi, M; Oikarinen, S; Veijola, R; Simell, O; Ilonen, J; Knip, M; Hyöty, H; Tauriainen, S

    2013-09-01

    Human parechoviruses (HPeVs) are RNA viruses associated mainly with mild gastrointestinal and respiratory infections in children and also cause neonatal sepsis and CNS infections. Human enteroviruses, close relatives of HPeVs, associate with the development of type 1 diabetes. In this study, the potential role of HPeV infections in promoting beta cell autoimmunity was investigated by analyzing stool samples of 54 prediabetic case and 134 healthy control children for the presence of HPeV RNA and comparing the derived infection frequencies. All 188 children were participants of the Finnish prospective Diabetes Prediction and Prevention study. Viral RNA was screened for using an HPeV-specific RT-PCR method coupled to liquid hybridization of the PCR product. The overall HPeV infection frequency did not differ between prediabetic case and control children. However, case boys had more HPeV positive samples in the 6-month period before becoming autoantibody positive, when compared to the matching time-period in controls (P < 0.01). HPeV infection at a young age does not appear to play a major role in the development of beta-cell autoimmunity. In boys, however, HPeVs showed time-dependent association with the first detection of diabetes-associated autoantibodies. Thus, in boys, HPeV infections cannot be excluded as a gender-specific risk factor which promotes the development of type 1 diabetes. PMID:23852688

  3. 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. PMID:23216278

  4. 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. PMID:26306600

  5. Comprehensive analysis of the ubiquitinome during oncogene-induced senescence in human fibroblasts

    PubMed Central

    Bengsch, Fee; Tu, Zhigang; Tang, Hsin-Yao; Zhu, Hengrui; Speicher, David W; Zhang, Rugang

    2015-01-01

    Oncogene-induced senescence (OIS) is an important tumor suppression mechanism preventing uncontrolled proliferation in response to aberrant oncogenic signaling. The profound functional and morphological remodelling of the senescent cell involves extensive changes. In particular, alterations in protein ubiquitination during senescence have not been systematically analyzed previously. Here, we report the first global ubiquitination profile of primary human cells undergoing senescence. We employed a well-characterized in vitro model of OIS, primary human fibroblasts expressing oncogenic RAS. To compare the ubiquitinome of RAS-induced OIS and controls, ubiquitinated peptides were enriched by immune affinity purification and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified 4,472 ubiquitination sites, with 397 sites significantly changed (>3 standard deviations) in senescent cells. In addition, we performed mass spectrometry analysis of total proteins in OIS and control cells to account for parallel changes in both protein abundance and ubiquitin levels that did not affect the percentage of ubiquitination of a given protein. Pathway analysis revealed that the OIS-induced ubiquitinome alterations mainly affected 3 signaling networks: eIF2 signaling, eIF4/p70S6K signaling, and mTOR signaling. Interestingly, the majority of the changed ubiquitinated proteins in these pathways belong to the translation machinery. This includes several translation initiation factors (eIF2C2, eIF2B4, eIF3I, eIF3L, eIF4A1) and elongation factors (eEF1G, eEF1A) as well as 40S (RPS4X, RPS7, RPS11 and RPS20) and 60S ribosomal subunits (RPL10, RPL11, RPL18 and RPL35a). In addition, we observed enriched ubiquitination of aminoacyl-tRNA ligases (isoleucyl-, glutamine-, and tyrosine-tRNA ligase), which provide the amino acid-loaded tRNAs for protein synthesis. These results suggest that ubiquitination affects key components of the translation machinery to regulate

  6. A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer

    PubMed Central

    Chattopadhyay, Koushik

    2011-01-01

    Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV) infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ‘HPV’, ‘cervical’, ‘CIN’, ‘polymorphism(s)’, ‘cervical’+ *the name of the gene* and ‘HPV’+ *the name of the gene*. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals. PMID:22345983

  7. A comprehensive analysis of microRNA expression during human keratinocyte differentiation in vitro and in vivo.

    PubMed

    Hildebrand, Janosch; Rütze, Martin; Walz, Nicole; Gallinat, Stefan; Wenck, Horst; Deppert, Wolfgang; Grundhoff, Adam; Knott, Anja

    2011-01-01

    Here, we report a comprehensive investigation of changes in microRNA (miRNA) expression profiles on human keratinocyte (HK) differentiation in vitro and in vivo. We have monitored expression patterns of 377 miRNAs during calcium-induced differentiation of primary HKs, and have compared these patterns with miRNA expression profiles of epidermal stem cells, transient amplifying cells, and terminally differentiated HKs from human skin. Apart from the previously described miR-203, we found an additional nine miRNAs (miR-23b, miR-95, miR-210, miR-224, miR-26a, miR-200a, miR-27b, miR-328, and miR-376a) that are associated with HK differentiation in vitro and in vivo. In situ hybridization experiments confirmed miR-23b as a marker of HK differentiation in vivo. Additionally, gene ontology analysis and functional validation of predicted miRNA targets using 3'-untranslated region-luciferase assays suggest that multiple miRNAs that are upregulated on HK differentiation cooperate to regulate gene expression during skin development. Our results thus provide the basis for further analysis of miRNA functions during epidermal differentiation. PMID:20827281

  8. pseudoMap: an innovative and comprehensive resource for identification of siRNA-mediated mechanisms in human transcribed pseudogenes.

    PubMed

    Chan, Wen-Ling; Yang, Wen-Kuang; Huang, Hsien-Da; Chang, Jan-Gowth

    2013-01-01

    RNA interference (RNAi) is a gene silencing process within living cells, which is controlled by the RNA-induced silencing complex with a sequence-specific manner. In flies and mice, the pseudogene transcripts can be processed into short interfering RNAs (siRNAs) that regulate protein-coding genes through the RNAi pathway. Following these findings, we construct an innovative and comprehensive database to elucidate siRNA-mediated mechanism in human transcribed pseudogenes (TPGs). To investigate TPG producing siRNAs that regulate protein-coding genes, we mapped the TPGs to small RNAs (sRNAs) that were supported by publicly deep sequencing data from various sRNA libraries and constructed the TPG-derived siRNA-target interactions. In addition, we also presented that TPGs can act as a target for miRNAs that actually regulate the parental gene. To enable the systematic compilation and updating of these results and additional information, we have developed a database, pseudoMap, capturing various types of information, including sequence data, TPG and cognate annotation, deep sequencing data, RNA-folding structure, gene expression profiles, miRNA annotation and target prediction. As our knowledge, pseudoMap is the first database to demonstrate two mechanisms of human TPGs: encoding siRNAs and decoying miRNAs that target the parental gene. pseudoMap is freely accessible at http://pseudomap.mbc.nctu.edu.tw/. Database URL: http://pseudomap.mbc.nctu.edu.tw/ PMID:23396300

  9. Comprehensive assessment of the global and regional vascular responses to food ingestion in humans using novel rapid MRI.

    PubMed

    Hauser, Jakob A; Muthurangu, Vivek; Steeden, Jennifer A; Taylor, Andrew M; Jones, Alexander

    2016-03-15

    Ingestion of food is known to increase mesenteric blood flow. It is not clear whether this increased flow demand is compensated by a rise in cardiac output (CO) alone or by redistribution of blood flow from other organs. We used a new comprehensive imaging method to assess the human cardiovascular response to food ingestion. Following a 12-h fast, blood flow in segments of the aorta and in organ-specific arteries, and ventricular volumes were assessed in 20 healthy adults using MRI at rest and following ingestion of a high-energy liquid meal. Systemic vascular resistance (SVR) fell substantially and CO rose significantly. Blood pressure remained stable. These changes were predominantly driven by a rapid fall in mesenteric vascular resistance, resulting in over four times more intestinal blood flow. Renal vascular resistance also declined but less dramatically. No changes in blood flow to the celiac territory, the brain, or the limbs were observed. In conclusion, this is the first study to fully characterize systemic and regional changes in vascular resistance after food ingestion in humans. Our findings show that the postprandial drop in SVR is fully compensated for by increased CO and not by redistribution of blood from other organs. With the exception of a modest increase in renal blood flow, there was no evidence of altered blood flow to nondigestive organs. The proposed oral food challenge protocol can be applied safely in an MRI environment and may be useful for studying the involvement of the gut in systemic or cardiovascular disease. PMID:26764056

  10. A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans.

    PubMed

    Michel, Martin C; Mayoux, Eric; Vallon, Volker

    2015-08-01

    Empagliflozin (formerly known as BI 10773) is a potent, competitive, and selective inhibitor of the sodium glucose transporter SGLT2, which mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. Accordingly, empagliflozin treatment increased urinary glucose excretion. This has been observed across multiple species including humans and was reported under euglycemic conditions, in obesity and, most importantly, in type 2 diabetic patients and multiple animal models of type 2 diabetes and of type 1 diabetes. This led to a reduction in blood glucose, smaller blood glucose excursions during oral glucose tolerance tests, and, upon chronic treatment, a reduction in HbA1c in animal models and patients. In rodents, such effects were observed in early and late phases of experimental diabetes and were associated with preservation of pancreatic β-cell function. Combination studies in animals demonstrated that beneficial metabolic effects of empagliflozin may also manifest when added to other types of anti-hyperglycemic treatments including linagliptin and pioglitazone. While some anti-hyperglycemic drugs lead to weight gain, empagliflozin treatment was associated with reduced body weight in normoglycemic obese and non-obese animals despite an increased food intake, largely due to a loss of adipose tissue; on the other hand, empagliflozin preserved body weight in models of type 1 diabetes. Empagliflozin improved endothelial dysfunction in diabetic rats and arterial stiffness, reduced blood pressure in diabetic patients, and attenuated early signs of nephropathy in diabetic animal models. Taken together, the SGLT2 inhibitor empagliflozin improves glucose metabolism by enhancing urinary glucose excretion; upon chronic administration, at least in animal models, the reductions in blood glucose levels are associated with beneficial effects on cardiovascular and renal complications of diabetes. PMID:26108304

  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. PMID:26362317

  12. The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach.

    PubMed

    Nyalwidhe, Julius; Burch, Tanya; Bocca, Silvina; Cazares, Lisa; Green-Mitchell, Shamina; Cooke, Marissa; Birdsall, Paige; Basu, Gaurav; Semmes, O John; Oehninger, Sergio

    2013-04-01

    The objective of these studies was to identify differentially expressed peptides/proteins in the culture media of embryos grown during in vitro fertilization (IVF) treatment to establish their value as biomarkers predictive of implantation potential and live birth. Micro-droplets of embryo culture media from IVF patients (conditioned) and control media maintained under identical culture conditions were collected and frozen at -80°C on Days 2-3 of in vitro development prior to analysis. The embryos were transferred on Day 3. The peptides were affinity purified based on their physico-chemical properties and profiled by mass spectrometry for differential expression. The identified proteins were further characterized by western blot and ELISA, and absolute quantification was achieved by multiple reaction monitoring (MRM). We identified up to 14 differentially regulated peptides after capture using paramagnetic beads with different affinities. These differentially expressed peptides were used to generate genetic algorithms (GAs) with a recognition capability of 71-84% for embryo transfer cycles resulting in pregnancy and 75-89% for those with failed implantation. Several peptides were further identified as fragments of Apolipoprotein A-1, which showed consistent and significantly reduced expression in the embryo media samples from embryo transfer cycles resulting in viable pregnancies. Western blot and ELISA, as well as quantitative MRM results, were confirmatory. These results demonstrated that peptide/protein profiles from the culture medium during early human in vitro development can discriminate embryos with highest and lowest implantation competence following uterine transfer. Further prospective studies are needed to establish validated thresholds for clinical application. PMID:23247814

  13. 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

  14. Genotyping human papillomaviruses: Development and evaluation of a comprehensive DNA microarray☆, ☆☆

    PubMed Central

    Shen-Gunther, Jane; Rebeles, Jennifer

    2016-01-01

    Goals To define the analytical and clinical performance of a human papillomavirus (HPV) custom-designed microarray targeting the HPV L1 gene for viral genotyping. Methods Microarray probes were designed by cataloging the genome sequence of all 120 known HPV types to generate tiling probes using eArray® software against the unique L1 capsid gene segments targeted by MY09/11 and FAP59/64 primers. The microarray (1 slide×8 arrays×60 K features) synthesized in situ by inkjet printing was tested using synthetic type-specific HPV DNA and existing HPV DNA from cervical cytology. The synthetic HPV L1 segments (genotypes 6, 11, 16, 18, 31, 33, 35, 45, 53, 58, 66, 73, 83) were manufactured from sequences stored in the NCBI taxonomy database. Using the hybridization patterns of the synthetic HPV DNA as the Support Vector Machine classifier, HPV DNA from patient samples were genotyped and compared to antecedent DNA sequencing/BLAST® results for concordance. Results 16 cytology-derived HPV DNA samples and 13 synthetic type-specific HPV DNA samples were tested singly, in duplicate, or in combination on 40 arrays. The synthetic HPV DNA hybridization patterns were found to be uniquely distinctive to serve well as a classifier of unknown HPV-containing specimens. For the 16 HPV DNA+ samples classified, 15 were concordant with DNA sequencing results. In 6/16 (38%) samples, the microarray hybridization pattern revealed ≥2 concurrent HPV infections. Conclusion The novel “HPV Array” was sensitive and specific for detecting single and multiple infections. This proof-of-principle project demonstrated the accuracy and advantages of microarray technology for HPV genotyping. PMID:23200917

  15. 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

  16. Index, comprehensive microsatellite, and unified linkage maps of human chromosome 14 with cytogenetic tie points and a telomere microsatellite marker

    SciTech Connect

    Pandit, S.D.; Wang, Jen C.; Veile, R.A.

    1995-10-10

    Three sets of linkage maps (index, comprehensive microsatellite, and unified) have been constructed for human chromosome 14 based on genotypes from the CEPH reference pedigrees. The index maps consist of 18 microsatellite markers, with heterozygosities of at least 68% and intermarker spacing no greater than 11 cM. The sex-average comprehensive microsatellite map is 125 cM in length and includes 115 markers with 54 loci uniquely placed with odds for marker order of at least 1000:1. The sex-average index map length is 121 cM, and the female- and male-specific maps are l43 and 101 cM, respectively. A unified map was also constructed from 147 loci (162 marker systems), which includes 32 RFLP markers in addition to the 115 microsatellites. The sex-average length of the unified map is 128 cM with 69 loci uniquely placed. Our maps are anchored by a microsatellite telomere marker sCAW1 (D14S826), developed from a telomere YAC clone TYAC196, which extends the linkage map to the physical terminus of the long arm of chromosome 14. Furthermore, we have also physically mapped seven of the loci by fluorscence in situ hybridization of cosmid clones or Alu-PCR products amplified from YACs containing the marker sequences. Together with previously established cytogenetic map designations for other loci, our maps display links between genetic markers for 10 of 13 cytogenetic bands of chromosome 14 at the 550 genome band resolution. 54 refs., 4 figs., 4 tabs.

  17. A comprehensive in vitro investigation of a portable magnetic separator device for human blood detoxification.

    PubMed

    Chen, Haitao; Ebner, Armin D; Bockenfeld, Danny; Ritter, James A; Kaminski, Michael D; Liu, Xianqiao; Rempfer, Dietmar; Rosengart, Axel J

    2007-10-01

    A portable magnetic separator device is being developed for a proposed magnetically based detoxification system. In this paper, the performance of this device was evaluated via preliminary in vitro flow experiments using simple fluids and a separator unit consisting of one tube and two metal wires, each at the top and bottom of the tube. The effects of the following factors were observed: mean flow velocity U(o) (0.14-45 cm s(-1)), magnetic field strength micro(o)H(o) (0.125-0.50 T), wire size R(w) (0.125, 0.250 and 0.500 mm), wire length L(w) (2, 5 and 10 cm), wire materials (nickel, stainless steel 304 and 430) and tube size (outer radius R(o) = 0.30 mm and inner radius R(i) = 0.25 mm; R(o) = 0.50 mm and R(i) = 0.375 mm; and R(o) = 2.0 mm and R(i) = 1.0 mm). Our observations showed that the experimental results fit well with the corresponding theoretical results from the model we previously developed at a low flow velocity area (for example, U(o) < or = 20 cm s(-1)), strong external magnetic field (for example, > or = 0.30 T) and long wire length (for example, L(w) = 10 cm). The experimental results also showed that more than 90% capture efficiency is indeed achievable under moderate systemic and operational conditions. Pressure drop measurements revealed that the device could work well under human physiological and clinical conditions, and sphere buildup would not have any considerable effect on the pressure drop of the device. The breakthrough experiments demonstrated that a lower flow rate V, higher applied magnetic field micro(o)H(o) and diluted sphere suspension, i.e. lower C(o), would delay the breakthrough. All the results indicate the promise of this portable magnetic separator device to efficiently in vivo sequestrate nano-/micro-spheres from blood flow in the future magnetically based detoxification system. PMID:17881819

  18. A comprehensive analysis of low-back disorder risk and spinal loading during the transferring and repositioning of patients using different techniques.

    PubMed

    Marras, W S; Davis, K G; Kirking, B C; Bertsche, P K

    1999-07-01

    Although patient handlers suffer from low-back injuries at an alarming rate worldwide, there has been limited research quantifying the risk for the specific tasks performed by the patient handlers. The current study used both a comprehensive evaluation system (low-back disorder risk model) and theoretical model (biomechanical spinal loading model) to evaluate risk of LBD of 17 participants (12 experienced and five inexperienced) performing several patient handling tasks. Eight of the participants were female and nine were male. Several patient transfers were evaluated as well as repositioning of the patient in bed; these were performed with one and two people. The patient transfers were between bed and wheelchair (fixed and removable arms) and between commode chair and hospital chair. A 'standard' patient (a 50 kg co-operative female; non-weight bearing but had use of upper body) was used in all patient handling tasks. Overall, patient handling was found to be an extremely hazardous job that had substantial risk of causing a low-back injury whether with one or two patient handlers. The greatest risk was associated with the one-person transferring techniques with the actual task being performed having a limited effect. The repositioning techniques were found to have significant risk of LBD associated with them with the single hook method having the highest LBD risk and spinal loads that exceeded the tolerance limits (worst patient handling job). The two-person draw sheet repositioning technique had the lowest LBD risk and spinal loads but still had relatively high spinal loads and LBD risk. Thus, even the safest of tasks (of the tasks evaluated in this study) had significant risk. Additionally, the current study represented a 'best' case scenario since the patient was relatively light and co-operative. Thus, patient handling in real situations such as in a nursing home, would be expected to be worse. Therefore, to have an impact on LBD, it is necessary to provide

  19. 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.

  20. Risk.

    PubMed

    Cole, Stephen R; Hudgens, Michael G; Brookhart, M Alan; Westreich, Daniel

    2015-02-15

    The epidemiologist primarily studies transitions between states of health and disease. The purpose of the present article is to define a foundational parameter for such studies, namely risk. We begin simply and build to the setting in which there is more than 1 event type (i.e., competing risks or competing events), as well as more than 1 treatment or exposure level of interest. In the presence of competing events, the risks are a set of counterfactual cumulative incidence functions for each treatment. These risks can be depicted visually and summarized numerically. We use an example from the study of human immunodeficiency virus to illustrate concepts. PMID:25660080

  1. 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.

  2. Chronic aquatic environmental risks from exposure to human pharmaceuticals.

    PubMed

    Crane, Mark; Watts, Chris; Boucard, Tatiana

    2006-08-15

    This paper reviews current information on the chronic aquatic toxicity of human pharmaceuticals and how it should be measured. Chronic toxicity tests with Cyanobacteria are likely to be sensitive surrogates for both algae and other unicellular organisms, although possibly not for higher plants. In contrast, there is little evidence of a general need to perform chronic aquatic invertebrate tests for all human pharmaceuticals, although further acute-to-chronic ratio data are required for the main therapeutic classes and modes of action of pharmaceuticals before this issue can be fully resolved. Chronic fish tests may be necessary for some substances, but it is likely that these can be focused more accurately through use of information in mammalian toxicity datasets. For some substances and modes of action, life-cycle or partial life-cycle fish tests may be more relevant than reliance on early life-stage (ELS) tests, because the ELS test is unlikely to respond adequately to all pharmaceutical modes of action. Biomarkers may be useful in focusing research and testing efforts by identifying active substances and receptors of interest in aquatic species, and they may also be useful in field surveys for helping to establish possible cause and effect relationships. QSARs have been used by several authors to predict acute toxic effects, but predictions of chronic effects are currently hampered by the paucity of available chronic data to build predictive models. There seems to be no obvious reason why mixtures of pharmaceuticals in the environment should be treated in a different way to mixtures of other potentially hazardous substances. If mixture toxicity is considered to be an important environmental issue then all substances should be considered within an appropriate risk assessment framework. PMID:16762401

  3. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans

    PubMed Central

    de Courten, Barbora; Kurdiova, Timea; de Courten, Maximilian P. J.; Belan, Vitazoslav; Everaert, Inge; Vician, Marek; Teede, Helena; Gasperikova, Daniela; Aldini, Giancarlo; Derave, Wim; Ukropec, Jozef; Ukropcova, Barbara

    2015-01-01

    Background Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. Methods and Results Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. Conclusion Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease. PMID:26439389

  4. Comprehensive and Quantitative Profiling of the Human Sweat Submetabolome Using High-Performance Chemical Isotope Labeling LC-MS.

    PubMed

    Hooton, Kevin; Han, Wei; Li, Liang

    2016-07-19

    samples, thereby allowing the use of sweat as another human biofluid for comprehensive and quantitative metabolomics research. PMID:27351466

  5. 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

  6. 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…

  7. How to Improve Reading Comprehension in High-Risk Students: Effects of Class Practices in Grade 5

    ERIC Educational Resources Information Center

    Vanlaar, Gudrun; Denies, Katrijn; Vandecandelaere, Machteld; Van Damme, Jan; Verhaeghe, Jean Pierre; Pinxten, Maarten; De Fraine, Bieke

    2014-01-01

    This study investigated the effect of class practices on students' learning gains in reading comprehension in the 5th grade. A sample of 4,344 students in 283 classes in 176 schools was studied. Several class practices that have previously been demonstrated to be effective were tested while controlling for student characteristics and…

  8. Risk Comprehension and Judgments of Statistical Evidentiary Appeals: When a Picture Is Not Worth a Thousand Words

    ERIC Educational Resources Information Center

    Parrott, Roxanne; Silk, Kami; Dorgan, Kelly; Condit, Celeste; Harris, Tina

    2005-01-01

    Too little theory and research has considered the effects of communicating statistics in various forms on comprehension, perceptions of evidence quality, or evaluations of message persuasiveness. In a considered extension of Subjective Message Construct Theory (Morley, 1987), we advance a rationale relating evidence form to the formation of…

  9. Effectively Managing Nuclear Risk Through Human Performance Improvement

    SciTech Connect

    Coe, Richard; Lake, Patricia

    2003-09-01

    The U.S. commercial nuclear industry has just completed an outstanding decade of plant performance. Safety levels and electric production are at unprecedented high levels and continue to exceed even high industry goals. Nuclear energy continues to keep the highest priority on performance improvement programs and highly trained and qualified people that maintain its record setting safety and reliability of operations. While the industry has maintained a high level of performance, the advent of deregulation and the consolidation of nuclear power plant ownership, as well as the current climate for concern about both rising energy costs and the availability of power, have raised the standard for nuclear energy's level of competitiveness in today's market place. The resulting challenge is how to more effectively manage risk and to improve performance even further in a generally high-performing industry. One of the most effective ways to develop this culture is to apply the principles of Hum an Performance Technology, or HPT. HPT is a relatively new field. Its principles are derived from the research and practice of behavioral and cognitive psychologists, instructional technologists, training designers, organizational developers, and various human resource specialists. Using the principles of HPT can help the nuclear industry successfully meet ever-changing environmental and business demands.

  10. 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

  11. 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...

  12. 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

  13. 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…

  14. 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.

  15. WHO guidance grounded in a comprehensive approach to sexual and reproductive health and human rights: topical pre-exposure prophylaxis

    PubMed Central

    Lusti-Narasimhan, Manjula; Khosla, Rajat; Baggaley, Rachel; Temmerman, Marleen; McGrory, Elizabeth; Farley, Tim

    2014-01-01

    Introduction Two new microbicide products based on topical (vaginal) application of antiretroviral drugs – 1% tenofovir gel and the dapivirine ring – are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Discussion Given that these new topical PrEP products are designed to be woman initiated and will likely be delivered in reproductive health settings, it is important to ensure that the guidance be framed in the context of comprehensive sexual and reproductive health and human rights. In addition to the safety and effectiveness data resulting from clinical trials, and the regulatory approval required for new products, the WHO normative guidelines on the use of topical PrEP will be essential for rapid roll-out in countries. Conclusions Human rights standards and principles provide a framework for the provision of woman-initiated HIV prevention products. These include addressing issues related to the gender inequities which are linked to the provision of HIV-prevention, treatment and care for young girls and women. Effective programming for women and girls must therefore be based on understanding the local, social and community contexts of the AIDS epidemic in the country, and adapting HIV strategies and programmes accordingly. Such a framework therefore is needed not only to ensure optimal uptake of these new products by women and girls but also to address sociocultural barriers to women's and girls’ access to these products. PMID:25224620

  16. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:27071722

  18. 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

    2016-01-01

    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. PMID:27071722

  19. 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

  20. Human health risk implications of multiple sources of faecal indicator bacteria in a recreational waterbody.

    PubMed

    Soller, Jeffrey A; Schoen, Mary E; Varghese, Arun; Ichida, Audrey M; Boehm, Alexandria B; Eftim, Sorina; Ashbolt, Nicholas J; Ravenscroft, John E

    2014-12-01

    We simulate the influence of multiple sources of enterococci (ENT) as faecal indicator bacteria (FIB) 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 illustrate that risks vary with the proportion of culturable ENT in water bodies derived from these sources and estimate corresponding ENT densities that yield the same level of health protection that the recreational water quality criteria in the United States seeks (benchmark risk). The benchmark risk is based on epidemiological studies conducted in water bodies predominantly impacted by human faecal sources. The key result is that the risks from mixed sources are driven predominantly by the proportion of the contamination source with the greatest ability to cause human infection (potency), not necessarily the greatest source(s) of FIB. Predicted risks from exposures to mixtures comprised of approximately 30% ENT from human sources were up to 50% lower than the risks expected from purely human sources when contamination is recent and ENT levels are at the current water quality criteria levels (35 CFU 100 mL(-1)). For human/non-pathogenic, human/gull, human/pig, and human/chicken faecal mixtures with relatively low human contribution, the predicted culturable enterococci densities that correspond to the benchmark risk are substantially greater than the current water quality criteria values. These findings are important because they highlight the potential applicability of site specific water quality criteria for waters that are predominantly un-impacted by human sources. PMID:25222329

  1. HUMAN HEALTH MULTI-YEAR PLAN

    EPA Science Inventory

    EPA's human health research represents the Agency's only comprehensive program to address the limitations in human health risk assessment. The measurement-derived databases, models, and protocols developed through this research program will strengthen the scientific foundation fo...

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

    PubMed

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

    2016-04-01

    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

  3. 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. PMID:27362447

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

    PubMed Central

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

    2013-01-01

    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 difficulties 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 three 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. PMID:21741671

  5. Predictive power of the Braden scale for pressure sore risk in adult critical care patients: a comprehensive review.

    PubMed

    Cox, Jill

    2012-01-01

    Critical care is designed for managing the sickest patients within our healthcare system. Multiple factors associated with an increased likelihood of pressure ulcer development have been investigated in the critical care population. Nevertheless, there is a lack of consensus regarding which of these factors poses the greatest risk for pressure ulceration. While the Braden scale for pressure sore risk is the most commonly used tool for measuring pressure ulcer risk in the United States, research focusing on the cumulative Braden Scale score and subscale scores is lacking in the critical care population. This author conducted a literature review on pressure ulcer risk assessment in the critical care population, to include the predictive value of both the total score and the subscale scores. In this review, the subscales sensory perception, mobility, moisture, and friction/shear were found to be associated with an increased likelihood of pressure ulcer development; in contrast, the Activity and Nutrition subscales were not found to predict pressure ulcer development in this population. In order to more precisely quantify risk in the critically ill population, modification of the Braden scale or development of a critical care specific risk assessment tool may be indicated. PMID:22948495

  6. 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. PMID:26490887

  7. 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. PMID:25893826

  8. Assessment of Regional Human Health Risks from Lead Contamination in Yunnan Province, Southwestern China

    PubMed Central

    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 3years), 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. PMID:25893826

  9. 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

  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. Mapping the increasing risk of human alveolar echinococcosis in Limburg, The Netherlands.

    PubMed

    Takumi, K; Hegglin, D; Deplazes, P; Gottstein, B; Teunis, P; van der Giessen, J

    2012-05-01

    The parasite Echinococcus multilocularis was first detected in The Netherlands in 1996 and repeated studies have shown that the parasite subsequently spread in the local population of foxes in the province of Limburg. It was not possible to quantify the human risk of alveolar echinococcosis because no relationship between the amount of parasite eggs in the environment and the probability of infection in humans was known. Here, we used the spread of the parasite in The Netherlands as a predictor, together with recently published historical records of the epidemiology of alveolar echinococcosis in Switzerland, to achieve a relative quantification of the risk. Based on these analyses, the human risk in Limburg was simulated and up to three human cases are predicted by 2018. We conclude that the epidemiology of alveolar echinococcosis in The Netherlands might have changed from a period of negligible risk in the past to a period of increasing risk in the forthcoming years. PMID:21733269

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

    PubMed

    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

  13. 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

  14. Comprehensive analysis of human small RNA sequencing data provides insights into expression profiles and miRNA editing

    PubMed Central

    Gong, Jing; Wu, Yuliang; Zhang, Xiantong; Liao, Yifang; Sibanda, Vusumuzi Leroy; Liu, Wei; Guo, An-Yuan

    2014-01-01

    MicroRNAs (miRNAs) play key regulatory roles in various biological processes and diseases. A comprehensive analysis of large scale small RNA sequencing data (smRNA-seq) will be very helpful to explore tissue or disease specific miRNA markers and uncover miRNA variants. Here, we systematically analyzed 410 human smRNA-seq datasets, which samples are from 24 tissue/disease/cell lines. We tested the mapping strategies and found that it was necessary to make multiple-round mappings with different mismatch parameters. miRNA expression profiles revealed that on average ∼70% of known miRNAs were expressed at low level or not expressed (RPM < 1) in a sample and only ∼9% of known miRNAs were relatively highly expressed (RPM > 100). About 30% known miRNAs were not expressed in all of our used samples. The miRNA expression profiles were compiled into an online database (HMED, http://bioinfo.life.hust.edu.cn/smallRNA/). Dozens of tissue/disease specific miRNAs, disease/control dysregulated miRNAs and miRNAs with arm switching events were discovered. Further, we identified some highly confident editing sites including 24 A-to-I sites and 23 C-to-U sites. About half of them were widespread miRNA editing sites in different tissues. We characterized that the 2 types of editing sites have different features with regard to location, editing level and frequency. Our analyses for expression profiles, specific miRNA markers, arm switching, and editing sites, may provide valuable information for further studies of miRNA function and biomarker finding. PMID:25692236

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

    PubMed

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

    2016-03-01

    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

  16. 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…

  17. An Evaluation of Transplacental Carcinogenesis for Human Health Risk Assessment

    EPA Science Inventory

    Risk assessments take into account the sensitivity of the postnatal period to carcinogens through the application of age-dependent adjustment factors (ADAFs) (Barton et al. 2005). The prenatal period is also recognized to be sensitive but is typically not included into risk asse...

  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. Comprehensive analysis of microRNA expression in regionalized human neural progenitor cells reveals microRNA-10 as a caudalizing factor.

    PubMed

    Jönsson, Marie E; Nelander Wahlestedt, Jenny; Åkerblom, Malin; Kirkeby, Agnete; Malmevik, Josephine; Brattaas, Per Ludvik; Jakobsson, Johan; Parmar, Malin

    2015-09-15

    MicroRNAs (miRNAs) have been implicated in regulating multiple processes during brain development in various species. However, the function of miRNAs in human brain development remains largely unexplored. Here, we provide a comprehensive analysis of miRNA expression of regionalized neural progenitor cells derived from human embryonic stem cells and human foetal brain. We found miR-92b-3p and miR-130b-5p to be specifically associated with neural progenitors and several miRNAs that display both age-specific and region-specific expression patterns. Among these miRNAs, we identified miR-10 to be specifically expressed in the human hindbrain and spinal cord, while being absent from rostral regions. We found that miR-10 regulates a large number of genes enriched for functions including transcription, actin cytoskeleton and ephrin receptor signalling. When overexpressed, miR-10 influences caudalization of human neural progenitor cells. Together, these data confirm a role for miRNAs in establishing different human neural progenitor populations. This dataset also provides a comprehensive resource for future studies investigating the functional role of different miRNAs in human brain development. PMID:26395143

  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. Health risks encountered by Dutch medical students during an elective in the tropics and the quality and comprehensiveness of pre-and post-travel care

    PubMed Central

    2010-01-01

    Background Clinical and research electives abroad offer medical students many unique experiences. However, participating in an unfamiliar health-care setting combined with limited medical experience may place students at risk of illness. To improve pre-and post-travel care, we assessed the health risks and the quality and comprehensiveness of pre-and post-travel care in a cohort of Dutch medical students returning form an elective abroad. Methods All medical students who had performed an elective in the tropics between July 2006 and December 2008 were sent an informative email asking them to complete a web-based questionnaire. Results 180 of 242 (74%) students completed the questionnaire. Regarding the risk of bloodborne viral infection: 67% of all students and 32% of junior students engaged in procedures that constitute a risk of exposure to bloodborne viral infection, often in countries with high HIV prevalence rates. None of nine students who experienced possible or certain mucosal or percutaneous exposure to potentially infectious body fluids reported the exposure at the time it occurred and none used PEP. Regarding other health risks: 8 of 40 (20%) students stopped using mefloquine due to adverse effects. This left a sizeable proportion unprotected in countries that are hyperendemic for malaria. Post-travel screening for schistosomiasis, tuberculosis (tuberculin skin test) and carriage of methicillin-resistant Staphylococcus aureus (MRSA) encompassed approximately half of all students who should have been screened. Conclusions Based on the results of this study we have adopted an integral set of measures to reduce the health risks associated with an elective abroad. The pre and post-travel consult has been centralized and standardized as well as the distribution of PEP. In addition we have developed a mandatory module on Global Health for all medical students planning an elective abroad. PMID:21126347

  2. "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…

  3. 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.

  4. Site specific risk assessment of an energy-from-waste thermal treatment facility in Durham Region, Ontario, Canada. Part A: Human health risk assessment.

    PubMed

    Ollson, Christopher A; Knopper, Loren D; Whitfield Aslund, Melissa L; Jayasinghe, Ruwan

    2014-01-01

    The regions of Durham and York in Ontario, Canada have partnered to construct an energy-from-waste thermal treatment facility as part of a long term strategy for the management of their municipal solid waste. This paper presents the results of a comprehensive human health risk assessment for this facility. This assessment was based on extensive sampling of baseline environmental conditions (e.g., collection and analysis of air, soil, water, and biota samples) as well as detailed site specific modeling to predict facility-related emissions of 87 identified contaminants of potential concern. Emissions were estimated for both the approved initial operating design capacity of the facility (140,000 tonnes per year) and for the maximum design capacity (400,000 tonnes per year). For the 140,000 tonnes per year scenario, this assessment indicated that facility-related emissions are unlikely to cause adverse health risks to local residents, farmers, or other receptors (e.g., recreational users). For the 400,000 tonnes per year scenarios, slightly elevated risks were noted with respect to inhalation (hydrogen chloride) and infant consumption of breast milk (dioxins and furans), but only during predicted 'upset conditions' (i.e. facility start-up, shutdown, and loss of air pollution control) that represent unusual and/or transient occurrences. However, current provincial regulations require that additional environmental screening would be mandatory prior to expansion of the facility beyond the initial approved capacity (140,000 tonnes per year). Therefore, the potential risks due to upset conditions for the 400,000 tonnes per year scenario should be more closely investigated if future expansion is pursued. PMID:23911923

  5. 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. PMID:25809961

  6. Human influence on meteorological drought risk in Europe

    NASA Astrophysics Data System (ADS)

    Gudmundsson, L.; Seneviratne, S. I.

    2015-12-01

    Drought has affected 37% of the European Union's territory in the past three decades, triggering ecological and socio-economic damages and impacting more than 100 billion inhabitants. Climate change simulations project increased drought risk in southern Europe, and on the other hand decreased drought risk in the norther of the continent. Observed changes in water balance components and drought indicators do resemble the projected pattern. However, assessments of possible causes of the reported regional changes have yet been inconclusive. To resolve this, we first employ a data driven approach and estimate how the probability of exceptionally dry years is related to global warming. The results confirm that it is very likely that that drought risk in the Mediterranean has increased in response to global warming, whereas it is very likely that drought risk has decreased in Northern Europe. Subsequently we show that observed changes in drought risk can only be captured by climate models if anthropogenic radiative forcing is accounted for. The consistency of the observational estimates with model simulations suggests that it is very likely that past changes in drought risk are attributable to anthropogenic effects on the climate.

  7. 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.

  8. 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.

  9. Risks of alcohol consumption in laboratory studies involving human research participants.

    PubMed

    Wood, M D; Sher, K J

    2000-12-01

    Research protocols that include alcohol consumption raise a number of critical issues with regard to potential risks to research participants, researchers, and institutions. This article seeks to highlight some of these issues by presenting some of the potential risks and discussing relevant dimensions and parameters of these risks. Risks to individual research participants are the primary focus of concern, but consideration of risks associated with aspects of the experimental, contextual, and institutional setting are also considered. The authors conclude with recommendations for individuals conducting studies involving alcohol consumption by human research participants. PMID:11130151

  10. 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

  11. 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...

  12. Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis.

    PubMed Central

    Brind, J; Chinchilli, V M; Severs, W B; Summy-Long, J

    1996-01-01

    STUDY OBJECTIVE: To ascertain, from the published reports to date, whether or not a significantly increased risk of breast cancer is specifically attributable to a history of induced abortion, independent of spontaneous abortion and age at first full term pregnancy (or first live birth); to establish the relative magnitude of such risk increase as may be found, and to ascertain and quantify such risk increases as may pertain to particular subpopulations of women exposed to induced abortion; in particular, nulliparous women and parous women exposed before compared with after the first full term pregnancy. INCLUDED STUDIES: The meta-analysis includes all 28 published reports which include specific data on induced abortion and breast cancer incidence. Since some study data are presented in more than one report, the 28 reports were determined to constitute 23 independent studies. Overall induced abortion odds ratios and odds ratios for the different subpopulations were calculated using an average weighted according to the inverse of the variance. An overall unweighted average was also computed for comparison. No quality criteria were imposed, but a narrative review of all included studies is presented for the reader's use in assessing the quality of individual studies. EXCLUDED STUDIES: All 33 published reports including data on abortion and breast cancer incidence but either pertaining only to spontaneous abortion or to abortion without specification as to whether it was induced or spontaneous. These studies are listed for the reader's information. RESULTS: The overall odds ratio (for any induced abortion exposure; n = 21 studies) was 1.3 (95% confidence interval of 1.2, 1.4). For comparison, the unweighted overall odds ratio was 1.4 (1.3,1.6). The odds ratio for nulliparous women was 1.3 (1.0,1.6), that for abortion before the first term pregnancy in parous women was 1.5 (1.2,1.8), and that for abortion after the first term pregnancy was 1.3 (1.1,1.5). CONCLUSIONS

  13. Comprehensive and computational analysis of genes in human umbilical vein endothelial cells responsive to X-irradiation.

    PubMed

    Furusawa, Yukihiro; Zhao, Qing-Li; Hattori, Yuichi; Tabuchi, Yoshiaki; Iwasaki, Toshiyasu; Nomura, Takaharu; Kondo, Takashi

    2016-06-01

    Radiation exposure such as A-bomb or radiation therapy is considered a major health-risk factor for cardiovascular disease. In order to understand the molecular mechanisms underlying the inflammatory reaction frequently encountered in the vascular system after exposure to ionizing radiation, we carried out a global scale microarray and computational gene expression analyses on human umbilical endothelial cells (HUVECs) exposed to X-ray (2.5 Gy). The gene ontology analysis revealed that the down-regulated genes were associated with cell cycle regulation, whereas the up-regulated genes were associated with inflammatory responses, in particular, the type 1 interferon response. The computational analysis using ingenuity pathway analysis also identified a gene network containing the interferon response factor 7 (IRF7) and its transcriptional targets such as interferon-induced transcripts (IFITs) and Mx1, which have been known to be associated with inflammation in endothelial cells. The up-regulated genes and the gene network identified here may explain the inflammatory response induced by X-irradiation. These findings uncover part of the molecular basis of the mechanism(s) of the inflammatory disorder in response to X-irradiation in HUVECs. The dataset is publicly available at the Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.nih.gov/geo/) with accession number GSE76484. PMID:27275413

  14. Approaches towards training in human risk management of surgical technology.

    PubMed

    Geissler, Norman; Machno, Andrej; Sánchez-Peralta, Luisa F; Pagador, José Blas; Sánchez-Margallo, Francisco M; Korb, Werner

    2016-04-01

    A safe application of modern surgical technology and computer-assisted surgery devices is based on an operation by adequately trained surgeons who are familiar with the benefits and limitations of the devices. We analyzed the in-depth interviews with seven Spanish and 10 German surgeons. Together with other studies, this analysis highlights the need for specific training in technological competence for surgeons. One way to train technological competence is to help surgeons understanding the basic principles of medical devices as well as explaining the basic concepts of risk analysis and risk management. Based on this premise, a stage model for risk assessment was developed and adapted for the training of surgeons. This was developed further into a train the trainer (TTT) concept, which was then evaluated for two example cases. During TTT-training, the trainers (expert surgeons) performed a risk analysis for several medical devices. Afterwards, the trainers organized a surgical workshop for surgical trainees (resident surgeons), in which high-fidelity simulators and the original medical devices were used. The results showed that the surgeons performed the risk analysis correctly with the stage model and afterwards were able to successfully apply the results in the workshop context. PMID:27096765

  15. Human health and ecological risk assessment of soil-borne arsenic and lead: A site-specific risk assessment

    SciTech Connect

    Roy, M.; Epp, G.A.; Beukema, P.; Nieboer, E.

    1997-12-31

    Screening level site specific human health and ecological risk assessments (ERA) were conducted at a historical (1908--1921) smelting and refining site in the Niagara Region, Ontario in accordance with the recently released provincial and federal risk assessment guidelines. The purpose of the assessment was to evaluate the risk associated with elevated levels of arsenic and lead in surface soils, and to assess alternative remediation options, prior to property transfer. Future intended land use will be parkland and for the site to remain forested. The identification of potential receptors, exposure pathways, and end-points was conducted at the biological community-level. The ERA involved a toxic cue inventory of the core smelting and refining site, adjacent lands and a reference site. Development of remediation options was based on hazard assessment and the prediction of risks associated with arsenic contamination. An evaluation of remediation options and the selection of a preferred option are discussed.

  16. 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

  17. 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

  18. 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

  19. A comprehensive meta-analysis of ZNF804A SNPs in the risk of schizophrenia among Asian populations.

    PubMed

    Huang, Liang; Ohi, Kazutaka; Chang, Hong; Yu, Hao; Wu, Lichuan; Yue, Weihua; Zhang, Dai; Gao, Lei; Li, Ming

    2016-04-01

    Common variants in ZNF804A increased the risk of schizophrenia (and bipolar disorder), with low effect sizes in Europeans, which is in line with the polygenic nature of the illnesses, and implies that genetic analyses in small samples may not be sufficient to detect stable results. This notion is supported by the inconsistent replications of ZNF804A variations among individual small Asian samples, indicating the absence of definitive conclusions in this population. We collected psychiatric phenotypic and genetic data from Asian genome-wide association (GWA) and individual replication studies, which include up to 13,452 cases, 17,826 healthy controls, and 680 families, that is, the largest-scale study on ZNF804A in Asian populations to date. The European GWAS risk single nucleotide polymorphism (SNP) rs1344706 was nominally associated with schizophrenia in these Asian samples (one-tailed P = 4.26 × 10(-2) , odds ratio [OR] = 1.048), and the association was further strengthened when bipolar disorder data was also included (one-tailed P = 1.85 × 10(-2) , OR = 1.057). Besides, a non-synonymous SNP rs1366842 in the exon 4 of ZNF804A was also associated with schizophrenia (P = 9.96 × 10(-3) , OR = 1.095). We additionally analyzed other 163 SNPs covering ZNF804A region, but none of them showed any evidence of association. Though the two SNPs did not remain significant if we applied multiple corrections, our analysis should be interpreted as a primary replication study with in prior hypothesis, and rs1344706 and rs1366842 might confer a small but detectable risk of schizophrenia (and bipolar disorder) in Asians. Moreover, the current data suggest the necessity of replication analyses in a large enough scale samples. PMID:26866941

  20. MTHFR C677T and A1298C polymorphisms and risk of lung cancer: a comprehensive evaluation.

    PubMed

    Yang, Y; Yang, L J; Deng, M Z; Luo, Y Y; Wu, S; Xiong, L; Wang, D; Liu, Y; Liu, H

    2016-01-01

    Results from previous studies on the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and lung cancer have been conflicting. The aim of this meta-analysis was to clarify the effect of MTHFR polymorphisms on the risk of lung cancer. An electronic search of PubMed, EMBASE, the Cochrane library, and the China Knowledge Resource Integrated Database for papers on C677T and A1298C and susceptibility to lung cancer was performed. The STATA software (Version 13.0) was used for statistical analysis. Statistical heterogeneity, tests of publication bias, and a sensitivity analysis were performed. Twenty-six studies on C677T (12,324 cases and 12,532 controls) and thirteen studies on A1298C (6773 cases and 8207 controls) were included in the meta-analysis. The MTHFR C677T polymorphism showed significant pooled ORs for the homozygote comparison (TT versus CC: OR = 1.518, 95%CI = 1.220-1.890), heterozygote comparison (CT versus CC: OR = 1.053, 95%CI = 0.940-1.179), dominant model (CT + TT versus CC: OR = 1.143, 95%CI = 1.013-1.291), recessive model (TT versus CT + CC: OR = 1.435, 95%CI = 1.190-1.730), and additive model (T versus C: OR = 1.176, 95%CI = 1.066-1.298). In summary, our meta-analysis showed that the MTHFR C677T polymorphism is associated with a significant increase in lung cancer risk in Asian and overall populations, but not in Caucasian populations. However, no significant association between the MTHFR A1298C polymorphism and lung cancer risk was found in either the Caucasian or Asian group with any genetic models. PMID:27173216

  1. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    PubMed

    Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T; Morgan, Alex A; Moreno-Estrada, Andres; Nilsen, Geoffrey B; Ruau, David; Lincoln, Stephen E; Bustamante, Carlos D; Butte, Atul J

    2012-01-01

    Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed

  2. Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases

    PubMed Central

    Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T.; Morgan, Alex A.; Moreno-Estrada, Andres; Nilsen, Geoffrey B.; Ruau, David; Lincoln, Stephen E.; Bustamante, Carlos D.; Butte, Atul J.

    2012-01-01

    Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed

  3. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment

    PubMed Central

    Cotney, Justin; Muhle, Rebecca A.; Sanders, Stephan J.; Liu, Li; Willsey, A. Jeremy; Niu, Wei; Liu, Wenzhong; Klei, Lambertus; Lei, Jing; Yin, Jun; Reilly, Steven K.; Tebbenkamp, Andrew T.; Bichsel, Candace; Pletikos, Mihovil; Sestan, Nenad; Roeder, Kathryn; State, Matthew W.; Devlin, Bernie; Noonan, James P.

    2015-01-01

    Recent studies implicate chromatin modifiers in autism spectrum disorder (ASD) through the identification of recurrent de novo loss of function mutations in affected individuals. ASD risk genes are co-expressed in human midfetal cortex, suggesting that ASD risk genes converge in specific regulatory networks during neurodevelopment. To elucidate such networks, we identify genes targeted by CHD8, a chromodomain helicase strongly associated with ASD, in human midfetal brain, human neural stem cells (hNSCs) and embryonic mouse cortex. CHD8 targets are strongly enriched for other ASD risk genes in both human and mouse neurodevelopment, and converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in dysregulation of ASD risk genes directly targeted by CHD8. Integration of CHD8-binding data into ASD risk models improves detection of risk genes. These results suggest loss of CHD8 contributes to ASD by perturbing an ancient gene regulatory network during human brain development. PMID:25752243

  4. An Updated and Comprehensive Meta-Analysis of Association Between Seven Hot Loci Polymorphisms from Eight GWAS and Glioma Risk.

    PubMed

    Wu, Qiang; Peng, Yanyan; Zhao, Xiaotao

    2016-09-01

    Eight genome-wide association studies (GWASs) found that seven loci (rs2736100, rs4295627, rs4977756, rs498872, rs11979158, rs2252586, rs6010620) polymorphisms could elevate the risk of glioma, one of the most common types of primary brain cancer in adults. However, the replication studies about these seven loci obtained inconsistent results. In order to derive a more accurate estimation about the relationship between the selected single-nucleotide polymorphism (SNP) and susceptibility to glioma, we conducted a meta-analysis containing all eligible published case control studies to evaluate the association. An overall literature search was conducted using the database of PubMed, Science Direct, China national knowledge infrastructure (CNKI), and Embase. Seventeen articles with 25 studies were included in the meta-analysis. Glioma risk (odds ratio, OR; 95 % confidential interval, 95 %CI) was estimated with the random-effect model or the fixed-effects model. STATA 12.0 was applied to analyze all statistical data. Results showed that seven hot loci were all associated with increased risk of glioma (rs2736100, OR = 1.28, 95 %CI = 1.23-1.32; rs4295627, OR = 1.34, 95 %CI = 1.21-1.47; rs4977756, OR = 1.24, 95 %CI = 1.20-1.28; rs498872, OR = 1.24, 95 %CI = 1.15-1.33; rs6010620, OR = 1.29, 95 %CI = 1.24-1.35; rs11979158: OR = 1.18, 95 %CI = 1.10-1.25; rs2252586: OR = 1.18, 95 %CI = 1.10-1.25). Additionally, subgroup analysis by stages of glioma found that variation of rs11979158 had stronger relationship with high-grade (OR = 1.32, 95 %CI = 1.19-1.45) than low-grade glioma (OR = 1.12, 95 % CI = 1.03-1.21). Similarly, stratified analysis of rs2252586 by stages revealed the similar trend, with OR of 1.26 (95 %CI = 1.17-1.35) in high-grade glioma and OR of 1.15 (95 %CI = 1.08-1.22) in low-grade glioma. In summary, the present study showed that mutations of the seven loci could elevate

  5. Anthropic shadow: observation selection effects and human extinction risks.

    PubMed

    Cirković, Milan M; Sandberg, Anders; Bostrom, Nick

    2010-10-01

    We describe a significant practical consequence of taking anthropic biases into account in deriving predictions for rare stochastic catastrophic events. The risks associated with catastrophes such as asteroidal/cometary impacts, supervolcanic episodes, and explosions of supernovae/gamma-ray bursts are based on their observed frequencies. As a result, the frequencies of catastrophes that destroy or are otherwise incompatible with the existence of observers are systematically underestimated. We describe the consequences of this anthropic bias for estimation of catastrophic risks, and suggest some directions for future work. PMID:20626690

  6. 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. PMID:20532563

  7. 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

  8. 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. PMID:24367549

  9. 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

  10. 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.

  11. Risk Management Structured for Today's Environment

    NASA Technical Reports Server (NTRS)

    Greenfield, Michael A.

    1998-01-01

    In NPG (NASA Procedures and Guidelines) 7120.5A, we define risk management as "an organized, systematic decision-making process that efficiently identifies, analyzes, plans, tracks, controls, and communicates and documents risk in order to increase the likelihood of achieving program/project goals." Effective risk management depends upon a thorough understanding of the concept of risk, the principles of risk management and the formation of a disciplined risk management process. In human spaceflight programs, NASA has always maintained a rigorous and highly structured risk management effort. When lives are at stake, NASA's missions must be 100% safe; the risk management approach used in human spaceflight has always been comprehensive.

  12. 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...

  13. 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. PMID

  14. 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

  15. Comprehensive analysis of regional human-driven environmental change with multitemporal remote sensing images using observed object-specified dynamic Bayesian network

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Hua, Yi; Ren, Qinglong; Zhang, Ye

    2016-01-01

    Traditional remote sensing change-detection algorithms only generate change-detection map and few quantitative evaluation indicators as the results, but they are unable to provide comprehensive analysis and further understanding of the detected changes. Aiming to assess regional development, we develop a comprehensive analysis method for human-driven environmental change by multitemporal remote sensing images. In order to adapt to analyze the time-varying multiple changed objects, an observed object-specified dynamic Bayesian network (i.e., OOS-DBN) is first proposed to adjust DBN structure and variables. Using semantic analysis for the relationship between multiple changed objects and regional development, all levels of situations and evidences (i.e., detected attributes of changed objects) are extracted as hidden variables and observed variables and inputted to OOS-DBN. Furthermore, conditional probabilities are computed by levels and time slices in OOS-DBN, resulting in the comprehensive analysis results. The experiments on the coastal region in Huludao, China, from 2003 to 2014 demonstrate that comprehensive analysis of changes reflecting that reclamation, construction of infrastructure, and New Huludao port contributed to the regional development. During four time slices, this region experienced rapid and medium-speed development, whose corresponding probabilities are 0.90, 0.87, 0.41, and 0.54, respectively, which is consistent with our field surveys.

  16. 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...

  17. 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...

  18. Risk calculations for hereditary effects of ionizing radiation in humans.

    PubMed

    Vogel, F

    1992-05-01

    A prediction of the extent to which an additional dose of ionizing radiation increases the natural germ cell mutation rate, and how much such an increase will affect the health status of future human populations is part of the service that human geneticists are expected to offer to human society. However, more detailed scrutiny of the difficulties involved reveals an extremely complex set of problems. A large number of questions arises before such a prediction can be given with confidence; many such questions cannot be answered at our present state of knowledge. However, such predictions have recently been attempted. The 1988 report of the United Nations Scientific Committee for the Effects of Atomic Radiation and the fifth report of the Committee on Biological Effects of Ionizing Radiation of the US National Research Council have presented a discussion of the human genetics problems involved. Empirical data from studies on children of highly radiation-exposed parents, e.g. parents exposed to the atomic bombs of Hiroshima and Nagasaki, or parents belonging to populations living on soil with high background radiation, have been mentioned in this context. Whereas precise predictions are impossible as yet because of deficiencies in our knowledge of medical genetics at various levels, the bulk of the existing evidence points to only small effects of low or moderate radiation doses, effects that will probably be buried in the "background noise" of changing patterns of human morbidity and mortality. PMID:1587523

  19. Avian GIS models signal human risk for West Nile virus in Mississippi

    PubMed Central

    Cooke, William H; Grala, Katarzyna; Wallis, Robert C

    2006-01-01

    Background West Nile virus (WNV) poses a significant health risk for residents of Mississippi. Physicians and state health officials are interested in new and efficient methods for monitoring disease spread and predicting future outbreaks. Geographic Information Systems (GIS) models have the potential to support these efforts. Environmental conditions favorable for mosquito habitat were modeled using GIS to derive WNV risk maps for Mississippi. Variables important to WNV dissemination were selected and classified as static and dynamic. The static variables included road density, stream density, slope, and vegetation. The dynamic variable represented seasonal water budget and was calculated using precipitation and evaporation estimates. Significance tests provided deterministic evidence of variable importance to the models. Results Several models were developed to estimate WNV risk including a landscape-base model and seasonal climatic sub-models. P-values from t-tests guided variable importance ranking. Variables were ranked and weights assigned as follows: road density (0.4), stream density (0.3), slope (0.2) and vegetation (0.1). This landscape-base model was modified by climatic conditions to assess the importance of climate to WNV risk. Human case data at the zip code level were used to validate modeling results. All models were summarized by zip codes for interpretation and model validation. For all models, estimated risk was higher for zip codes with at least one human case than for zip codes where no human cases were recorded. Overall median measure of risk by zip code indicated that 67% of human cases occurred in the high-risk category. Conclusion Modeling results indicated that dead bird occurrences are correlated with human WNV risk and can facilitate the assessment of environmental variables that contribute to that risk. Each variable's importance in GIS-based risk predictions was assigned deterministically. Our models indicated non-uniform distribution

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

    PubMed

    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

  1. Communicating Numerical Risk: Human Factors That Aid Understanding in Health Care

    PubMed Central

    Brust-Renck, Priscila G.; Royer, Caisa E.; Reyna, Valerie F.

    2014-01-01

    In this chapter, we review evidence from the human factors literature that verbal and visual formats can help increase the understanding of numerical risk information in health care. These visual representations of risk are grounded in empirically supported theory. As background, we first review research showing that people often have difficulty understanding numerical risks and benefits in health information. In particular, we discuss how understanding the meanings of numbers results in healthier decisions. Then, we discuss the processes that determine how communication of numerical risks can enhance (or degrade) health judgments and decisions. Specifically, we examine two different approaches to risk communication: a traditional approach and fuzzy-trace theory. Applying research on the complications of understanding and communicating risks, we then highlight how different visual representations are best suited to communicating different risk messages (i.e., their gist). In particular, we review verbal and visual messages that highlight gist representations that can better communicate health information and improve informed decision making. This discussion is informed by human factors theories and methods, which involve the study of how to maximize the interaction between humans and the tools they use. Finally, we present implications and recommendations for future research on human factors in health care. PMID:24999307

  2. Myiasis as a risk factor for prion diseases in humans.

    PubMed

    Lupi, O

    2006-10-01

    Prion diseases are transmissible spongiform encephalopathies of humans and animals. The oral route is clearly associated with some prion diseases, according to the dissemination of bovine spongiform encephalopathy (BSE or mad cow disease) in cattle and kuru in humans. However, other prion diseases such as scrapie (in sheep) and chronic wasting disease (CWD) (in cervids) cannot be explained in this way and are probably more associated with a pattern of horizontal transmission in both domestic and wild animals. The skin and mucous membranes are a potential target for prion infections because keratinocytes and lymphocytes are susceptible to the abnormal infective isoform of the prion protein. Iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) was also recognized after corneal transplants in humans and scrapie was successfully transmitted to mice after ocular instillation of infected brain tissue, confirming that these new routes could also be important in prion infections. Some ectoparasites have been proven to harbour prion rods in laboratory experiments. Prion rods were identified in both fly larvae and pupae; adult flies are also able to express prion proteins. The most common causes of myiasis in cattle and sheep, closely related animals with previous prion infections, are Hypoderma bovis and Oestrus ovis, respectively. Both species of flies present a life cycle very different from human myiasis, as they have a long contact with neurological structures, such as spinal canal and epidural fat, which are potentially rich in prion rods. Ophthalmomyiases in humans is commonly caused by both species of fly larvae worldwide, providing almost direct contact with the central nervous system (CNS). The high expression of the prion protein on the skin and mucosa and the severity of the inflammatory response to the larvae could readily increase the efficiency of transmission of prions in both animals and humans. PMID:16987255

  3. 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. PMID:16537191

  4. A risk for non-sexual transmission of human papillomavirus?

    PubMed

    Ryndock, Eric J; Meyers, Craig

    2014-10-01

    Human papillomaviruses (HPVs) are estimated to be the most common sexually transmitted virus in humans. The virus is of great interest as it is the etiological agent of cervical cancer. Sexual transmission of HPV is generally accepted, however, non-sexual transmission of the virus is often debated. Here, we review the evidence from basic research and clinical studies that show HPV can survive well outside of its host to potentially be transmitted by non-sexual means. In doing so, we hope to discover problems in current prevention practices and show a need for better disinfectants to combat the spread of HPV. PMID:25199987

  5. 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.

  6. A comprehensive approach to environmental and human factors into product/service design and development. A review from an ergoecological perspective.

    PubMed

    Saravia-Pinilla, Martha H; Daza-Beltrán, Carolina; García-Acosta, Gabriel

    2016-11-01

    This article presents the results of a documentary-exploratory review of design methods and concepts associated with human and environmental factors, based on a qualitative-quantitative analysis of coincidences with the fundamentals of ergoecology and in line with sustainable dynamics, with a view to putting the principles of ergoecology into practice in product/service design and development. 61.6% of 696 documents found represent work on conceptual developments, while the remaining 38.4% refer to design methods. Searches were refined using Nvivo-10 software, and 101 documents were obtained about theoretical aspects while 17 focused on the application of methods, and these formed the analysis universe. The results show how little concern there is for working comprehensively on human and environmental aspects, and a trend toward segmentation of human and environmental aspects in the field of product/service design and development can be seen, at both concept and application/methodology levels. It was concluded from the above that comprehensive, simultaneous work is needed on human and environmental aspects, clarity and conceptual unity, in order to achieve sustainability in practical matters and ensure that ergoecology-compatible design methods are applied. PMID:26725206

  7. 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

  8. Total Human Exposure Risk Database and Advance Simulaiton Environment

    EPA Science Inventory

    THERdbASE is no longer supported by EPA and is no longer available as download.

    THERdbASE is a collection of databases and models that are useful to assist in conducting assessments of human exposure to chemical pollutants, especial...

  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. PMID:24447116

  10. Puberty as a critical risk period for eating disorders: a review of human and animal studies.

    PubMed

    Klump, Kelly L

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. PMID:23998681

  11. Human health risk assessment: selected Internet and world wide web resources.

    PubMed

    Patterson, Jacqueline; Hakkinen, P J Bert; Wullenweber, Andrea E

    2002-04-25

    The world wide web (WWW) has become a valuable source of 24 hour-a-day access to information needed by human health risk assessors. Various web sites and other Internet resources provide information needed for human hazard identification, dose-response evaluation, exposure assessment, risk characterization, and risk management. Information on risk communication is also available. Substantial collections of information on multiple aspects of risk assessment are found in sites sponsored by RiskWorld, the (US) EPA's National Center for Environmental Assessment (NCEA), the (US) National Library of Medicine's TOXNET, the (US) Agency for Toxic Substances and Disease Registry (ATSDR), and the International Programme on Chemical Safety (IPCS). Also valuable are various web sites providing information on the physical and chemical properties of chemicals, the environmental fate and transport of chemicals, government regulations, and guidance and training for performing risk assessments. Several professional societies and other organizations have web sites addressing risk assessment issues and information, and there are Internet mailing lists for online help and for sharing information and perspectives. We classify selected web sites according to user needs and provide the reader with a collection of selected sites that can serve as entry points to risk assessment-related web resources. PMID:11955689

  12. Dog-associated risk factors for human plague.

    PubMed

    Gould, L Hannah; Pape, J; Ettestad, P; Griffith, K S; Mead, P S

    2008-10-01

    Plague is a rare but often fatal zoonosis endemic to the western United States. Previous studies have identified contact with pets as a potential risk factor for infection. We conducted a matched case-control study to better define the risks associated with pets at both the household and individual levels. Using a written questionnaire, we surveyed nine surviving plague patients, 12 household members of these patients, and 30 age- and neighbourhood-matched controls about household and individual exposures. Overall, 79% of households had at least one dog, 59% had at least one cat and 33% used flea control, with no significant differences between case and control households. Four (44%) case households reported having a sick dog versus no (0%) control households [matched odds ratio, (mOR) 18.5, 95% confidence interval (CI) 2.3-infinity], and four (44%) patients reported sleeping in the same bed with a pet dog versus three (10%) controls (mOR 5.7, 95% CI 1.0-31.6). Within case households with multiple members, two (40%) of five patients slept with their dogs versus none (0%) of 12 healthy family members (P=0.13). The exposures to cats were not significant. Sleeping in the same bed as a pet dog remained significantly associated with infection in a multivariate logistic regression model (P=0.046). Our findings suggest that dogs may facilitate the transfer of fleas into the home and that activities with close extended contacts with dogs may increase the risk of plague infection. PMID:18489541

  13. Comprehensive Planning.

    ERIC Educational Resources Information Center

    Pavlenko, Victor V.

    Comprehensive planning, defined as the work of those who engage in efforts, within a delimited geographic area, to identify and order the physical, social, and economic relationships of that area, is discussed in the four sections of this paper. Section I, Introduction, describes what "planning" and "comprehensive planning" are. In Section II, Why…

  14. 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

  15. 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 PM10 and gaseous pollutants from a petroleum coke calciner facility. The ambient air pollutant levels were collected through monitors installed at multiple locations in the vicinity of the facility. The measured and modeled particulate levels in ambient air from the calciner facility were compared to standards protective of public health. The results indicated that exposure levels were, on occasions at sites farther from the facility, higher than the public health limit of 150 μg/m(3) 24-h average for PM10. However, the carbon fraction demonstrated that the contribution from the calciner facility was de minimis. Exposure levels of the modeled SO2, CO, NOx and PM10 concentrations were also below public health air quality standards. These results demonstrate that emissions from calcining processes involving petroleum coke, at facilities that are well controlled, are below regulatory standards and are not expected to produce a public health risk. PMID:26520182

  16. Human exposure and risk from indoor use of chlorpyrifos.

    PubMed Central

    Gibson, J E; Peterson, R K; Shurdut, B A

    1998-01-01

    The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in juxtaposition with two recent articles in Environmental Health Perspectives concerning potential exposures to children. In studies conducted according to EPA guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity does not occur in the absence of significant cholinesterase inhibition. If exposures are less than those that cause significant cholinesterase depression, then no signs or symptoms related to chlorpyrifos exposure occur. The weight of empirical evidence indicates that the risk of adults or children experiencing an adverse health effect from exposure to chlorpyrifos through both nondietary and dietary sources is negligible. Both the research supporting the registration of these products and their long history of widespread use suggest that unless these products are seriously misused, their margins of safety are wide enough to protect everyone with the potential to be exposed. A weight-of-evidence review of the entire scientific knowledge base relating to chlorpyrifos products supports these conclusions. PMID:9618344

  17. Mining the potential interrelationships between human health and ecological risk assessments of metal-contaminated sites

    SciTech Connect

    Appling, J.W.

    1994-12-31

    Conservative approaches to human health or ecological risk assessment often result in evaluations that indicate a risk at metal concentrations near or below background levels. This presents a complex dilemma to regulators, responsible parties, and the public: How can risk be more realistically estimated so that the public is not unnecessarily alarmed into thinking normal exposures pose abnormal risk, and site remediation can be responsible yet cost-effective? One answer is using-ecological and human health studies together to improve the quality of both types of assessments. Mammalian herbivores and roving children are good spatial and temporal integrators of exposure; biomarkers or Monte Carlo-based models of exposure to herbivores can support realistic estimates of exposure to children. Reduced bioavailability of metals in soils at mining sites is well recognized for many metals and is amenable to study in ecological species; such studies reduce the overestimate of risk to humans through direct contact or exposure via the food chain. Recent and current human health studies of lead and arsenic bioavailability also support ecological assessments. Mixtures of metals pose special challenges because of the potential for antagonistic, additive, or synergistic effects with respect to bioavailability, absorption, distribution, excretion, toxic effects and nutritional or physiological essentiality. Combining results from pharmacokinetic, mechanistic, and environmental studies of mixtures enhances the predictive abilities of risk assessments.

  18. Human health and performance risk management—an approach for exploration missions

    NASA Astrophysics Data System (ADS)

    Davis, Jeffrey R.; Fogarty, Jennifer A.; Richard, Elizabeth E.

    During long duration exploration missions, maintaining human health and performance will be essential to enabling success. Therefore, NASA has developed standards through the Health and Medical Technical Authority to insure human health and performance during exploration. Human health standards are the first step in defining acceptable risk for human space flight and take into consideration both short-term (mission) and long-term (lifetime) health risk. These standards are based on the best medical evidence from terrestrial standards; analog spaceflight environments; and spaceflight experience. Standards drive the development of focused program requirements to mitigate risks associated with specific missions. Program requirements include vehicle design as well as health care systems including medical, environmental and countermeasures. NASA has also developed the risk mitigation analysis tool (RMAT), a process to evaluate the effectiveness of risk mitigation strategies. The RMAT facilitates documentation and analysis of the effectiveness of mitigation strategies, enables NASA to baseline a risk mitigation approach based on the best evidence, and provides the traceability from research and technology development projects to specific mission deliverables.

  19. Assessing the Risks to Human Health in Heterogeneous Aquifers under Uncertainty

    NASA Astrophysics Data System (ADS)

    de Barros, Felipe

    2015-04-01

    Reliable quantification of human health risk from toxic chemicals present in groundwater is a challenging task. The main difficulty relies on the fact that many of the components that constitute human health risk assessment are uncertain and requires interdisciplinary knowledge. Understanding the impact from each of these components in risk estimation can provide guidance for decision makers to manage contaminated sites and best allocate resources towards minimal prediction uncertainty. This presentation will focus on the impact of aquifer heterogeneity in human health risk. Spatial heterogeneity of the hydrogeological properties can lead to the formation of preferential flow channels which control the plume spreading rates and travel time statistics, both which are critical in assessing the risk level. By making use of an integrated hydrogeological-health stochastic framework, the significance of characteristic length scales (e.g. characterizing flow, transport and sampling devices) in both controlling the uncertainty of health risk and determining data needs is highlighted. Through a series of examples, we show how fundamental knowledge on the main physical mechanisms affecting solute pathways are necessary to understand the human health response to varying drivers.

  20. 77 FR 56202 - Notification of an External Peer Review Meeting for the Draft Framework for Human Health Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... for Human Health Risk Assessment to Inform Decision Making. Any member of the public may register to... on the draft document, Framework for Human Health Risk Assessment to Inform Decision Making will be... improve the utility of risk assessment in the decision-making process. In developing the draft...

  1. Adequacy of human reliability data for addressing risk reduction issues at commercial nuclear power plants

    SciTech Connect

    Ryan, T.G.; O'Brien, J.N.; Spettell, C.M.

    1985-01-01

    This paper describes the results of an assessment of how well currently available Probabilistic Risk Assessment (PRA) data address a representative set of human risk issues of current concern to the US Nuclear Regulatory Commission (NRC). A three-step process was used to make that assessment. First, all Human Reliability Analysis (HRA) data included in 19 PRAs were identified, collected, and stored on a computer. Second, a list of human risk ''working level issues'' of concern to NRC was compiled. Finally, the HRA/PRA data which were collected from 19 PRAs were compared to the data needs to assess the extent to which currently available PRA data are useful in addressing human risk issues of concern to NRC. Less than 1% of the data needs were determined to be addressed by currently available PRA data. Findings indicate that PRA data could be far more useful in addressing human risk issues with modification of the development process and documentation structure of PRAs. In addition, information from non-PRA sources could be integrated with PRA data to address many other issues. 7 refs., 13 tabs.

  2. Human health risk assessment from exposure to trihalomethanes in Canadian cities.

    PubMed

    Chowdhury, Shakhawat; Hall, Kevin

    2010-07-01

    Lifetime exposure to trihalomethanes (THMs) through ingestion, inhalation and dermal contacts may pose risks to human health. Current approaches may under predict THMs exposure by using THMs in cold water during showering and bathing. Warming of chlorinated water during showering may increase THMs formation through reactions between organics and residual chlorine, which can increase human health risks. In this study, THMs concentrations in shower water were estimated using THMs rate increase model. Using cold water THMs, exposure through ingestion was estimated, while THMs exposure during showering was estimated using THMs in warm water. Human health cancer risks and additional expenses for 20 most populated Canadian cities from exposure to THMs were estimated. Inhalation and dermal contact during showering contributed 30% to 50% of total cancer risks, while risks from inhalation and dermal contacts were comparable for all cities. Overall cancer risks were estimated between 7.2 x 10(-6) and 6.4 x 10(-5) for these cities. Cancer incidents were estimated highest for Montreal (94/year) followed by Toronto (53/year), which may require additional medical expenses of 18.8 and 10.7 million dollars/year for Montreal and Toronto respectively. Cancer risks from exposure to THMs can be controlled by reducing THMs in water supply and varying shower stall volume, shower duration and air exchange rate in shower stall. PMID:20434775

  3. Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons

    PubMed Central

    Yoshimizu, Takao; Pan, Jen Q.; Mungenast, Alison E.; Madison, Jon M.; Su, Susan; Ketterman, Josh; Ongur, Dost; McPhie, Donna; Cohen, Bruce; Perlis, Roy; Tsai, Li-Huei

    2014-01-01

    Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia, and major depression, and a haplotype located in an intronic region of the L-type voltage gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant. We generated induced human neurons, or iN cells, from more than 20 individuals harboring homozygous risk genotypes, heterozygous, or homozygous non-risk genotypes at the rs1006737 locus. Using these iNs, we performed electrophysiology and quantitative PCR experiments that demonstrated increased L-type VGCC current density as well as increased mRNA expression of CACNA1C in induced neurons homozygous for the risk genotype, compared to non-risk genotypes. These studies demonstrate that the risk genotype at rs1006737 is associated with significant functional alterations in human induced neurons, and may direct future efforts at developing novel therapeutics for the treatment of psychiatric disease. PMID:25403839

  4. Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.

    PubMed

    Yoshimizu, T; Pan, J Q; Mungenast, A E; Madison, J M; Su, S; Ketterman, J; Ongur, D; McPhie, D; Cohen, B; Perlis, R; Tsai, L-H

    2015-02-01

    Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia and major depression, and a haplotype located in an intronic region of the L-type voltage-gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant. We generated induced human neurons, or iN cells, from more than 20 individuals harboring homozygous risk genotypes, heterozygous or homozygous non-risk genotypes at the rs1006737 locus. Using these iNs, we performed electrophysiology and quantitative PCR experiments that demonstrated increased L-type VGCC current density as well as increased mRNA expression of CACNA1C in iNs homozygous for the risk genotype, compared with non-risk genotypes. These studies demonstrate that the risk genotype at rs1006737 is associated with significant functional alterations in human iNs, and may direct future efforts at developing novel therapeutics for the treatment of psychiatric disease. PMID:25403839

  5. A Model-based Framework for Risk Assessment in Human-Computer Controlled Systems

    NASA Technical Reports Server (NTRS)

    Hatanaka, Iwao

    2000-01-01

    The rapid growth of computer technology and innovation has played a significant role in the rise of computer automation of human tasks in modem production systems across all industries. Although the rationale for automation has been to eliminate "human error" or to relieve humans from manual repetitive tasks, various computer-related hazards and accidents have emerged as a direct result of increased system complexity attributed to computer automation. The risk assessment techniques utilized for electromechanical systems are not suitable for today's software-intensive systems or complex human-computer controlled systems. This thesis will propose a new systemic model-based framework for analyzing risk in safety-critical systems where both computers and humans are controlling safety-critical functions. A new systems accident model will be developed based upon modem systems theory and human cognitive processes to better characterize system accidents, the role of human operators, and the influence of software in its direct control of significant system functions. Better risk assessments will then be achievable through the application of this new framework to complex human-computer controlled systems.

  6. A Human-Health Risk Assessment for West Nile Virus and Insecticides Used in Mosquito Management

    PubMed Central

    Peterson, Robert K.D.; Macedo, Paula A.; Davis, Ryan S.

    2006-01-01

    West Nile virus (WNV) has been a major public health concern in North America since 1999, when the first outbreak in the Western Hemisphere occurred in New York City. As a result of this ongoing disease outbreak, management of mosquitoes that vector WNV throughout the United States and Canada has necessitated using insecticides in areas where they traditionally have not been used or have been used less frequently. This has resulted in concerns by the public about the risks from insecticide use. The objective of this study was to use reasonable worst-case risk assessment methodologies to evaluate human-health risks for WNV and the insecticides most commonly used to control adult mosquitoes. We evaluated documented health effects from WNV infection and determined potential population risks based on reported frequencies. We determined potential acute (1-day) and subchronic (90-day) multiroute residential exposures from each insecticide for several human subgroups during a WNV disease outbreak scenario. We then compared potential insecticide exposures to toxicologic and regulatory effect levels. Risk quotients (RQs, the ratio of exposure to toxicologic effect) were < 1.0 for all subgroups. Acute RQs ranged from 0.0004 to 0.4726, and subchronic RQs ranged from 0.00014 to 0.2074. Results from our risk assessment and the current weight of scientific evidence indicate that human-health risks from residential exposure to mosquito insecticides are low and are not likely to exceed levels of concern. Further, our results indicate that, based on human-health criteria, the risks from WNV exceed the risks from exposure to mosquito insecticides. PMID:16507459

  7. Human immunodeficiency virus infection, cardiovascular risk factor profile and risk for acute myocardial infarction

    PubMed Central

    Anne-Lise, Paisible; Chang, Chung-Chou H.; So-Armah, Kaku A.; Butt, Adeel A.; Leaf, David A.; Budoff, Matthew; Rimland, David; Bedimo, Roger; Goetz, Matthew B.; Rodriguez-Barradas, Maria C.; Crane, Heidi M.; Gibert, Cynthia L.; Brown, Sheldon T.; Tindle, Hilary A.; Warner, Alberta L.; Alcorn, Charles; Skanderson, Melissa; Justice, Amy C.; Freiberg, Matthew

    2015-01-01

    Background Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV infected (HIV+) patients. We assessed the association between HIV and incident AMI within CVDRF strata. Methods Cohort 81322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study-Virtual Cohort (prospective study of HIV+ and matched HIV− veterans). Veterans were followed from first clinical encounter on/after 4/1/2003 until AMI/death/last follow-up date (12/31/2009). Predictors HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood-pressure (BP), BP medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ non-optimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome Incident AMI (defined using enzyme, EKG clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates). Statistics: Cox models adjusted for demographics, comorbidity, and substance use. Results 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared to HIV− veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared to HIV− veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0 95%CI: 1.0–3.9, p=0.044). Conclusion The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared to HIV− veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people. PMID:25588033

  8. Potential human health risks from metals and As via Odontesthes bonariensis consumption and ecological risk assessments in a eutrophic lake.

    PubMed

    Monferran, Magdalena V; Garnero, Paola Lorena; Wunderlin, Daniel A; Angeles Bistoni, María de Los

    2016-07-01

    The concentration of Al, Cr, Fe, Mn, Ni, Cu, Zn, Hg, Sr, Mo, Ag, Cd, Pb and As was analyzed in water, sediment, and muscle of Odontesthes bonariensis from the eutrophic San Roque Lake (Córdoba-Argentina). The monitoring campaign was performed during the wet, dry and intermediate season. The concentration of Cr, Fe, Pb, Zn, Al and Cd in water exceeded the limits considered as hazardous for aquatic life. The highest metal concentrations were observed in sediment, intermediate concentrations, in fish muscle, and the lowest in water, with the exception of Cr, Zn, As and Hg, which were the highest in fish muscle. Potential ecological risk analysis of heavy metal concentrations in sediment indicated that the San Roque Lake posed a low ecological risk in all sampling periods. The target hazard quotients (THQs) and carcinogenic risk (CR) for individual metals showed that As in muscle was particularly hazardous, posing a potential risk for fishermen and the general population during all sampling periods. Hg poses a potential risk for fishermen only in the intermediate season. It is important to highlight that none of these two elements exceeded the limits considered as hazardous for aquatic life in water and sediment. This result proves the importance of performing measurements of contaminants, in both abiotic and biotic compartments, to assess the quality of food resources. These results suggest that the consumption of this fish species from this reservoir is not completely safe for human health. PMID:27060257

  9. NEURAL PLASTICITY, HUMAN GENETICS, AND RISK FOR ALCOHOL DEPENDENCE

    PubMed Central

    Hill, Shirley Y.

    2013-01-01

    Opportunities for advances in the neurobiology of alcohol dependence have been facilitated by the development of sophisticated neurophysiological and neuroimaging techniques that allow us to have a window on developmental changes in brain structure and function. The search for genes that may increase susceptibility to alcohol dependence has been greatly facilitated by the recognition that intermediate phenotypes, sometimes referred to as endophenotypes. may be closer to the genetic variation than is the more complex alcohol dependence phenotype. This chapter will review the evidence that the brain is highly plastic, exhibiting major postnatal changes, especially during adolescence, in neural circuits that appear to influence addiction susceptibility. This chapter will suggest that heritable aspects of brain structure and function that are seen developmentally may be an important endophenotypic characteristic associated with familial risk for developing alcohol dependence. Finally, a review of studies showing associations between brain structural and functional characteristics and specific genes will be offered. PMID:20813240

  10. Factors governing risk of cougar attacks on humans

    USGS Publications Warehouse

    Mattson, David; Logan, Kenneth; Sweanor, Linda

    2011-01-01

    Since the 1980s wildlife managers in the United States and Canada have expressed increasing concern about the physical threat posed by cougars (Puma concolor) to humans. We developed a conceptual framework and analyzed 386 human–cougar encounters (29 fatal attacks, 171 instances of nonfatal contact, and 186 close-threatening encounters) to provide information relevant to public safety. We conceived of human injury and death as the outcome of 4 transitions affected by different suites of factors: (1) a human encountering a cougar: (2) given an encounter, odds that the cougar would be aggressive; (3) given aggression, odds that the cougar would attack; and (4) given an attack, odds that the human would die. We developed multivariable logistic regression models to explain variation in odds at transitions three and four using variables pertaining to characteristics of involved people and cougars. Young (≤ 2.5 years) or unhealthy (by weight, condition, or disease) cougars were more likely than any others to be involved in close (typically <5 m) encounters that threatened the involved person. Of cougars in close encounters, females were more likely than males to attack, and of attacking animals, adults were more likely than juveniles to kill the victim (32% versus 9% fatality, respectively). During close encounters, victims who used a weapon killed the involved cougar in 82% of cases. Other mitigating behaviors (e.g., yelling, backing away, throwing objects, increasing stature) also substantially lessened odds of attack. People who were moving quickly or erratically when an encounter happened (running, playing, skiing, snowshoeing, biking, ATV-riding) were more likely to be attacked and killed compared to people who were less active (25% versus 8% fatality). Children (≤ 10 years) were more likely than single adults to be attacked, but intervention by people of any age reduced odds of a child’s death by 4.6×. Overall, cougar attacks on people in Canada and the

  11. Environmental distribution and associated human health risk due to trace elements and organic compounds in soil in Jiangxi province, China.

    PubMed

    Teng, Yanguo; Li, Jiao; Wu, Jin; Lu, Sijin; Wang, Yeyao; Chen, Haiyang

    2015-12-01

    The government of China launched its first national soil quality and pollution survey (NSQPS) during April 2006 to December 2013. Data gathered in several earlier soil surveys were rarely used to understand the status of pollution. In this study, the dataset collected at the provincial level was analyzed for the first time. Concentrations, distribution, diversity, and human health risks of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, V and Zn) and organic pollutants (benzene hexachloride (BHCs), dichlorodiphenyltrichloroethanes (DDTs), phthalic acid esters (PAEs), polycyclic aromatic hydrocarbon (PAHs), polychlorinated biphenyls (PCBs), and petroleum hydrocarbons (PHCs)) in surface soil samples collected across Jiangxi province,China were presented. The results showed that, the proportion of contaminants with concentrations higher than their corresponding regulatory reference value ranged from 0.12% to 17%. It is worth note that, the local residents are exposed to moderate non-carcinogenic and carcinogenic risks at some sites. The comprehensive analysis of soil pollutants provide baseline information for establishing a long-term soil environmental monitoring program in Jiangxi province, China. PMID:26363984

  12. The Importance of HRA in Human Space Flight: Understanding the Risks

    NASA Technical Reports Server (NTRS)

    Hamlin, Teri

    2010-01-01

    Human performance is critical to crew safety during space missions. Humans interact with hardware and software during ground processing, normal flight, and in response to events. Human interactions with hardware and software can cause Loss of Crew and/or Vehicle (LOCV) through improper actions, or may prevent LOCV through recovery and control actions. Humans have the ability to deal with complex situations and system interactions beyond the capability of machines. Human Reliability Analysis (HRA) is a method used to qualitatively and quantitatively assess the occurrence of human failures that affect availability and reliability of complex systems. Modeling human actions with their corresponding failure probabilities in a Probabilistic Risk Assessment (PRA) provides a more complete picture of system risks and risk contributions. A high-quality HRA can provide valuable information on potential areas for improvement, including training, procedures, human interfaces design, and the need for automation. Modeling human error has always been a challenge in part because performance data is not always readily available. For spaceflight, the challenge is amplified not only because of the small number of participants and limited amount of performance data available, but also due to the lack of definition of the unique factors influencing human performance in space. These factors, called performance shaping factors in HRA terminology, are used in HRA techniques to modify basic human error probabilities in order to capture the context of an analyzed task. Many of the human error modeling techniques were developed within the context of nuclear power plants and therefore the methodologies do not address spaceflight factors such as the effects of microgravity and longer duration missions. This presentation will describe the types of human error risks which have shown up as risk drivers in the Shuttle PRA which may be applicable to commercial space flight. As with other large PRAs

  13. Toxicology and risk assessment of coumarin: focus on human data.

    PubMed

    Abraham, Klaus; Wöhrlin, Friederike; Lindtner, Oliver; Heinemeyer, Gerhard; Lampen, Alfonso

    2010-02-01

    Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI. PMID:20024932

  14. Managing uncertainties of hazard risks - adaptation strategies to sustain human security

    NASA Astrophysics Data System (ADS)

    Liotta, P.; Klose, C. D.

    2010-12-01

    With regard to severities of natural forces events, measures to mitigate associated hazard risks take place under high uncertainties (i.e., information entropy). In terms of decision making, this fog of uncertainties “tends to make things seem grotesque and larger than they really are." (v. Clausewitz) Thus, expected socioeconomic risks associated with nature- or human-triggered hazards range over a wide spectrum and make decision making processes often cumbersome (e.g, 2005 Hurricane Katrina, 2010 Mexican Golf coast oil spills). Here, we present strategies with several tactical measures to mitigate expected risks and improve human security. Both, hazard and vulnerability mitigation/reduction strategies will be discussed in the context of nature-triggered hazards (e.g., volcanic, atmospheric events) and human-triggered hazards (e.g., earthquakes, environmental changes).

  15. Risk Factors for Human Infection with Puumala Virus, Southwestern Germany

    PubMed Central

    Ranft, Ulrich; Piechotowski, Isolde; Childs, James E.; Brockmann, Stefan O.

    2009-01-01

    Puumala virus, which causes nephropathia epidemica (NE), is the most prevalent hantavirus in Germany; bank voles serve as the main reservoir. During 2001–2007, most NE cases reported from Germany occurred in the southwestern state of Baden-Württemberg. We investigated the influence of bank vole habitats (beech forest, seed plants), vole food supply (beechnut mast), climate factors (winter and spring temperatures), and human population density on spatial and temporal occurrence of NE cases in Baden-Württemberg. Using Poisson-regression analyses, we found that all these factors influenced disease incidence. Furthermore, an independent trend of increasing incidence predicted that incidence will nearly double each year. The regression model explained 75% of the annual variation in NE incidence. The results suggest that environmental drivers lead to increasing incidence of NE infections in the southern part or even other parts of Germany. PMID:19624917

  16. [Genetically modified foods. Advantages and human health risks].

    PubMed

    Filip, Lorena; Miere, Doina; Indrei, L L

    2004-01-01

    One of the most important issue with which the mankind is confronting now is related to the quantitatively as well as qualitatively assurance of the food supply necessary for human species existence. In this context, by means of genetic engineering, modified genetic organisms were obtained. In the first stage, plant crops with high productivity and resistant against diseases and pests were obtained. After that, food products having modified organoleptic properties and high nutrition values were produced. The main problem concerning the long-term consumption of these products is their toxicity, which until now was not confirmed or denied. For this reason, tests are necessary to be made in order to stipulate and prevent these effects. PMID:16004228

  17. Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?

    PubMed

    Evans, Richard M; Martin, Olwenn V; Faust, Michael; Kortenkamp, Andreas

    2016-02-01

    Current chemicals regulation operates almost exclusively on a chemical-by-chemical basis, however there is concern that this approach may not be sufficiently protective if two or more chemicals have the same toxic effect. Humans are indisputably exposed to more than one chemical at a time, for example to the multiple chemicals found in food, air and drinking water, and in household and consumer products, and in cosmetics. Assessment of cumulative risk to human health and/or the environment from multiple chemicals and routes can be done in a mixture risk assessment (MRA). Whilst there is a broad consensus on the basic science of mixture toxicology, the path to regulatory implementation of MRA within chemical risk assessment is less clear. In this discussion piece we pose an open question: should the scope of human MRA cross legislative remits or 'silos'? We define silos as, for instance, legislation that defines risk assessment practice for a subset of chemicals, usually on the basis of substance/product, media or process orientation. Currently any form of legal mandate for human MRA in the EU is limited to only a few pieces of legislation. We describe two lines of evidence, illustrated with selected examples, that are particularly pertinent to this question: 1) evidence that mixture effects have been shown for chemicals regulated in different silos and 2) evidence that humans are co-exposed to chemicals from different silos. We substantiate the position that, because there is no reason why chemicals allocated to specific regulatory silos would have non-overlapping risk profiles, then there is also no reason to expect that MRA limited only to chemicals within one silo can fully capture the risk that may be present to human consumers. Finally, we discuss possible options for implementation of MRA and we hope to prompt wider discussion of this issue. PMID:26573369

  18. Evaluating the Impact of Contaminant Dilution and Biodegradation in Uncertainty Quantification of Human Health Risk

    NASA Astrophysics Data System (ADS)

    Zarlenga, Antonio; de Barros, Felipe; Fiori, Aldo

    2016-04-01

    We present a probabilistic framework for assessing human health risk due to groundwater contamination. Our goal is to quantify how physical hydrogeological and biochemical parameters control the magnitude and uncertainty of human health risk. Our methodology captures the whole risk chain from the aquifer contamination to the tap water assumption by human population. The contaminant concentration, the key parameter for the risk estimation, is governed by the interplay between the large-scale advection, caused by heterogeneity and the degradation processes strictly related to the local scale dispersion processes. The core of the hazard identification and of the methodology is the reactive transport model: erratic displacement of contaminant in groundwater, due to the spatial variability of hydraulic conductivity (K), is characterized by a first-order Lagrangian stochastic model; different dynamics are considered as possible ways of biodegradation in aerobic and anaerobic conditions. With the goal of quantifying uncertainty, the Beta distribution is assumed for the concentration probability density function (pdf) model, while different levels of approximation are explored for the estimation of the one-point concentration moments. The information pertaining the flow and transport is connected with a proper dose response assessment which generally involves the estimation of physiological parameters of the exposed population. Human health response depends on the exposed individual metabolism (e.g. variability) and is subject to uncertainty. Therefore, the health parameters are intrinsically a stochastic. As a consequence, we provide an integrated in a global probabilistic human health risk framework which allows the propagation of the uncertainty from multiple sources. The final result, the health risk pdf, is expressed as function of a few relevant, physically-based parameters such as the size of the injection area, the Péclet number, the K structure metrics and

  19. The Comprehensive, Powerful, Academic Database (CPAD): An Evaluative