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Sample records for affect human safety

  1. 76 FR 65734 - Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ...-Affected Food Crops for Human Consumption; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Guidance for Industry: Evaluating the Safety of Flood-Affected Food Crops for Human Consumption... information on how to evaluate the safety of flood-affected food crops for human consumption. DATES:...

  2. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  3. Does our sleep debt affect patients’ safety?

    PubMed Central

    Tewari, Anurag; Soliz, Jose; Billota, Federico; Garg, Shuchita; Singh, Harsimran

    2011-01-01

    The provision of anaesthesia requires a high level of knowledge, sound judgement, fast and accurate responses to clinical situations, and the capacity for extended periods of vigilance. With changing expectations and arising medico-legal issues, anaesthesiologists are working round the clock to provide efficient and timely health care services, but little is thought whether the “sleep provider” is having adequate sleep. Decreased performance of motor and cognitive functions in a fatigued anaesthesiologist may result in impaired judgement, late and inadequate responses to clinical changes, poor communication and inadequate record keeping, all of which affect the patient safety, showing without doubt the association of sleep debt to the adverse events and critical incidents. Perhaps it is time that these issues be promptly addressed to prevent the silent perpetuation of a problem that is pertinent to our health and our profession. We endeavour to focus on the evidence that links patient safety to fatigue and sleepiness of health care workers and specifically on anaesthesiologists. The implications of sleep debt are deep on patient safety and strategies to prevent this are the need of the hour. PMID:21431047

  4. Radar: Human Safety Net

    ERIC Educational Resources Information Center

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  5. Space Station crew safety - Human factors model

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.; Junge, M. K.

    1984-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this Space Station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  6. Motivational and organizational factors affecting implementation of worker safety training.

    PubMed

    Lindell, M K

    1994-01-01

    Training is unlikely to affect behavior on the job if the worker views it as unnecessary. This chapter describes types of safety behaviors and training activities, the implementation of safety training, current perspectives on motivation, and other motivational and organizational factors affecting the implementation of worker safety training.

  7. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

    PubMed

    Maas Enriquez, Monika; Thrift, John; Garger, Stephen; Katterle, Yvonne

    2016-11-01

    BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A.

  8. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

    PubMed

    Maas Enriquez, Monika; Thrift, John; Garger, Stephen; Katterle, Yvonne

    2016-11-01

    BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A. PMID:27436242

  9. [Reactor safety and human failure].

    PubMed

    Smidt, D

    1979-12-01

    Reactor safety is given by the reliable solution of 3 tasks: on-time shutdown, continuous decay-heat removal, safe containment. After describing the general strategy of their solution even under upset conditions the most important engineered safeguards of pressurized water reactors are summarized. The important problem of human failure is discussed in some more detail. For the example Harrisburg some difficulties, but also some technical countermeasures are illustrated. PMID:537639

  10. Trends affecting hospitals' human resources.

    PubMed

    Neudeck, M M

    1985-01-01

    Hospital workers at every level--from administrators to housekeepers--will be affected by the interaction of changes already underway in the healthcare industry. Societal forces that will affect the hospital workforce include demographic change, the rise of the participatory ethic and decentralization, a growing philosophy of job entitlement, and new pressures for unionization. At the same time, the industry is faced with changing manpower requirements, cost containment, and the oversupply of physicians. This article identifies some of the likely effects of these changes on hospital human resources and suggests ways that administrators can prepare for them.

  11. Safety and the Human Factor.

    ERIC Educational Resources Information Center

    Smith, Ann

    1982-01-01

    Discusses four elements of safety programs: (1) safety training; (2) safety inspections; (3) accident investigations; and (4) protective safety equipment. Also discusses safety considerations in water/wastewater treatment facilities focusing on falls, drowning hazards, trickling filters, confined space entry, collection/distribution system safety,…

  12. Improving Safety through Human Factors Engineering.

    PubMed

    Siewert, Bettina; Hochman, Mary G

    2015-10-01

    Human factors engineering (HFE) focuses on the design and analysis of interactive systems that involve people, technical equipment, and work environment. HFE is informed by knowledge of human characteristics. It complements existing patient safety efforts by specifically taking into consideration that, as humans, frontline staff will inevitably make mistakes. Therefore, the systems with which they interact should be designed for the anticipation and mitigation of human errors. The goal of HFE is to optimize the interaction of humans with their work environment and technical equipment to maximize safety and efficiency. Special safeguards include usability testing, standardization of processes, and use of checklists and forcing functions. However, the effectiveness of the safety program and resiliency of the organization depend on timely reporting of all safety events independent of patient harm, including perceived potential risks, bad outcomes that occur even when proper protocols have been followed, and episodes of "improvisation" when formal guidelines are found not to exist. Therefore, an institution must adopt a robust culture of safety, where the focus is shifted from blaming individuals for errors to preventing future errors, and where barriers to speaking up-including barriers introduced by steep authority gradients-are minimized. This requires creation of formal guidelines to address safety concerns, establishment of unified teams with open communication and shared responsibility for patient safety, and education of managers and senior physicians to perceive the reporting of safety concerns as a benefit rather than a threat. PMID:26466179

  13. Arthropods affecting the human eye.

    PubMed

    Panadero-Fontán, Rosario; Otranto, Domenico

    2015-02-28

    Ocular infestations by arthropods consist in the parasitization of the human eye, either directly (e.g., some insect larvae causing ophthalmomyiasis) or via arthropods feeding on lachrymal/conjunctival secretions (e.g., some eye-seeking insects, which also act as vectors of eye pathogens). In addition, demodicosis and phthiriasis may also cause eye discomfort in humans. Ophthalmomyiasis by larvae of the families Oestridae, Calliphoridae and Sarcophagidae, are frequent causative agents of human ocular infestations. Over the last decades, the extensive use of macrocyclic lactones in cattle has reduced the frequency of infestations by Hypoderma bovis and Hypoderma lineatum (family Oestridae), and consequently, human infestations by these species. A prompt diagnosis of ocular myiasis (e.g., by serological tests) is pivotal for positive prognoses, particularly when the larvae are not detectable during the ophthalmologic examination. Molecular diagnoses may also assist physicians and parasitologists in achieving time-efficient diagnoses of infestations by Oestridae causing myiasis. Finally, due to widespread international travel to exotic destinations, cases of myiasis are increasing in non-endemic areas, therefore requiring physicians to acquire a profound knowledge of the clinical symptoms linked to these infestations to prevent costly, inappropriate treatments or severe complications. PMID:25620292

  14. Arthropods affecting the human eye.

    PubMed

    Panadero-Fontán, Rosario; Otranto, Domenico

    2015-02-28

    Ocular infestations by arthropods consist in the parasitization of the human eye, either directly (e.g., some insect larvae causing ophthalmomyiasis) or via arthropods feeding on lachrymal/conjunctival secretions (e.g., some eye-seeking insects, which also act as vectors of eye pathogens). In addition, demodicosis and phthiriasis may also cause eye discomfort in humans. Ophthalmomyiasis by larvae of the families Oestridae, Calliphoridae and Sarcophagidae, are frequent causative agents of human ocular infestations. Over the last decades, the extensive use of macrocyclic lactones in cattle has reduced the frequency of infestations by Hypoderma bovis and Hypoderma lineatum (family Oestridae), and consequently, human infestations by these species. A prompt diagnosis of ocular myiasis (e.g., by serological tests) is pivotal for positive prognoses, particularly when the larvae are not detectable during the ophthalmologic examination. Molecular diagnoses may also assist physicians and parasitologists in achieving time-efficient diagnoses of infestations by Oestridae causing myiasis. Finally, due to widespread international travel to exotic destinations, cases of myiasis are increasing in non-endemic areas, therefore requiring physicians to acquire a profound knowledge of the clinical symptoms linked to these infestations to prevent costly, inappropriate treatments or severe complications.

  15. Human factors in safety and business management.

    PubMed

    Vogt, Joachim; Leonhardt, Jorg; Koper, Birgit; Pennig, Stefan

    2010-02-01

    Human factors in safety is concerned with all those factors that influence people and their behaviour in safety-critical situations. In aviation these are, for example, environmental factors in the cockpit, organisational factors such as shift work, human characteristics such as ability and motivation of staff. Careful consideration of human factors is necessary to improve health and safety at work by optimising the interaction of humans with their technical and social (team, supervisor) work environment. This provides considerable benefits for business by increasing efficiency and by preventing incidents/accidents. The aim of this paper is to suggest management tools for this purpose. Management tools such as balanced scorecards (BSC) are widespread instruments and also well known in aviation organisations. Only a few aviation organisations utilise management tools for human factors although they are the most important conditions in the safety management systems of aviation organisations. One reason for this is that human factors are difficult to measure and therefore also difficult to manage. Studies in other domains, such as workplace health promotion, indicate that BSC-based tools are useful for human factor management. Their mission is to develop a set of indicators that are sensitive to organisational performance and help identify driving forces as well as bottlenecks. Another tool presented in this paper is the Human Resources Performance Model (HPM). HPM facilitates the integrative assessment of human factors programmes on the basis of a systematic performance analysis of the whole system. Cause-effect relationships between system elements are defined in process models in a first step and validated empirically in a second step. Thus, a specific representation of the performance processes is developed, which ranges from individual behaviour to system performance. HPM is more analytic than BSC-based tools because HPM also asks why a certain factor is

  16. Human factors in safety and business management.

    PubMed

    Vogt, Joachim; Leonhardt, Jorg; Koper, Birgit; Pennig, Stefan

    2010-02-01

    Human factors in safety is concerned with all those factors that influence people and their behaviour in safety-critical situations. In aviation these are, for example, environmental factors in the cockpit, organisational factors such as shift work, human characteristics such as ability and motivation of staff. Careful consideration of human factors is necessary to improve health and safety at work by optimising the interaction of humans with their technical and social (team, supervisor) work environment. This provides considerable benefits for business by increasing efficiency and by preventing incidents/accidents. The aim of this paper is to suggest management tools for this purpose. Management tools such as balanced scorecards (BSC) are widespread instruments and also well known in aviation organisations. Only a few aviation organisations utilise management tools for human factors although they are the most important conditions in the safety management systems of aviation organisations. One reason for this is that human factors are difficult to measure and therefore also difficult to manage. Studies in other domains, such as workplace health promotion, indicate that BSC-based tools are useful for human factor management. Their mission is to develop a set of indicators that are sensitive to organisational performance and help identify driving forces as well as bottlenecks. Another tool presented in this paper is the Human Resources Performance Model (HPM). HPM facilitates the integrative assessment of human factors programmes on the basis of a systematic performance analysis of the whole system. Cause-effect relationships between system elements are defined in process models in a first step and validated empirically in a second step. Thus, a specific representation of the performance processes is developed, which ranges from individual behaviour to system performance. HPM is more analytic than BSC-based tools because HPM also asks why a certain factor is

  17. Space station crew safety: Human factors interaction model

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.; Junge, M. K.

    1985-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this space station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  18. Factors affecting quality and safety of fresh-cut produce.

    PubMed

    Francis, G A; Gallone, A; Nychas, G J; Sofos, J N; Colelli, G; Amodio, M L; Spano, G

    2012-01-01

    The quality of fresh-cut fruit and vegetable products includes a combination of attributes, such as appearance, texture, and flavor, as well as nutritional and safety aspects that determine their value to the consumer. Nutritionally, fruit and vegetables represent a good source of vitamins, minerals, and dietary fiber, and fresh-cut produce satisfies consumer demand for freshly prepared, convenient, healthy food. However, fresh-cut produce deteriorates faster than corresponding intact produce, as a result of damage caused by minimal processing, which accelerates many physiological changes that lead to a reduction in produce quality and shelf-life. The symptoms of produce deterioration include discoloration, increased oxidative browning at cut surfaces, flaccidity as a result of loss of water, and decreased nutritional value. Damaged plant tissues also represent a better substrate for growth of microorganisms, including spoilage microorganisms and foodborne pathogens. The risk of pathogen contamination and growth is one of the main safety concerns associated with fresh-cut produce, as highlighted by the increasing number of produce-linked foodborne outbreaks in recent years. The pathogens of major concern in fresh-cut produce are Listeria monocytogenes, pathogenic Escherichia coli mainly O157:H7, and Salmonella spp. This article describes the quality of fresh-cut produce, factors affecting quality, and various techniques for evaluating quality. In addition, the microbiological safety of fresh-cut produce and factors affecting pathogen survival and growth on fresh-cut produce are discussed in detail.

  19. How do humans affect wildlife nematodes?

    USGS Publications Warehouse

    Weinstein, Sara B.; Lafferty, Kevin D.

    2015-01-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host–parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  20. How do humans affect wildlife nematodes?

    PubMed

    Weinstein, Sara B; Lafferty, Kevin D

    2015-05-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host-parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  1. Human factors and safety in emergency medicine

    NASA Technical Reports Server (NTRS)

    Schaefer, H. G.; Helmreich, R. L.; Scheidegger, D.

    1994-01-01

    A model based on an input process and outcome conceptualisation is suggested to address safety-relevant factors in emergency medicine. As shown in other dynamic and demanding environments, human factors play a decisive role in attaining high quality service. Attitudes held by health-care providers, organisational shells and work-cultural parameters determine communication, conflict resolution and workload distribution within and between teams. These factors should be taken into account to improve outcomes such as operational integrity, job satisfaction and morale.

  2. Human safety in the lunar environment

    NASA Technical Reports Server (NTRS)

    Lewis, Robert H.

    1992-01-01

    Any attempt to establish a continuously staffed base or permanent settlement on the Moon must safely meet the challenges posed by the Moon's surface environment. This environment is drastically different from the Earth's, and radiation and meteoroids are significant hazards to human safety. These dangers may be mitigated through the use of underground habitats, the piling up of lunar materials as shielding, and the use of teleoperated devices for surface operations. The lunar environment is detailed along with concepts for survival.

  3. Safety of human papillomavirus vaccines: a review

    PubMed Central

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872

  4. Plant natural variability may affect safety assessment data.

    PubMed

    Batista, Rita; Oliveira, Margarida

    2010-12-01

    Before market introduction, genetic engineered (GE) food products, like any other novel food product, are subjected to extensive assessment of their potential effects on human health. In recent years, a number of profiling technologies have been explored aiming to increase the probability of detecting any unpredictable unintended effect and, consequently improving the efficiency of GE food safety assessment. These techniques still present limitations associated with the interpretation of the observed differences with respect to their biological relevance and toxicological significance. In order to address this issue, in this study, we have performed 2D-gel electrophoresis of five different ears of five different MON810 maize plants and of other five of the non-transgenic near-isogenic line. We have also performed 2D-gel electrophoresis of the pool of the five protein extractions of MON810 and control lines. We have notice that, in this example, the exclusive use of data from 2D-electrophoresed pooled samples, to compare these two lines, would be insufficient for an adequate safety evaluation. We conclude that, when using "omics" technologies, it is extremely important to eliminate all potential differences due to factors not related to the ones under study, and to understand the role of natural plant-to-plant variability in the encountered differences.

  5. National plan to enhance aviation safety through human factors improvements

    NASA Technical Reports Server (NTRS)

    Foushee, Clay

    1990-01-01

    The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

  6. Affective Biases in Humans and Animals.

    PubMed

    Robinson, E S J; Roiser, J P

    2016-01-01

    Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies. PMID:27660073

  7. Issues affecting advanced passive light-water reactor safety analysis

    SciTech Connect

    Beelman, R.J.; Fletcher, C.D.; Modro, S.M.

    1992-08-01

    Next generation commercial reactor designs emphasize enhanced safety through improved safety system reliability and performance by means of system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs wig necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing US advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes might require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.

  8. Issues affecting advanced passive light-water reactor safety analysis

    SciTech Connect

    Beelman, R.J.; Fletcher, C.D.; Modro, S.M.

    1992-01-01

    Next generation commercial reactor designs emphasize enhanced safety through improved safety system reliability and performance by means of system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs wig necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing US advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes might require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.

  9. Organizational factors affecting safety implementation in food companies in Thailand.

    PubMed

    Chinda, Thanwadee

    2014-01-01

    Thai food industry employs a massive number of skilled and unskilled workers. This may result in an industry with high incidences and accident rates. To improve safety and reduce the accident figures, this paper investigates factors influencing safety implementation in small, medium, and large food companies in Thailand. Five factors, i.e., management commitment, stakeholders' role, safety information and communication, supportive environment, and risk, are found important in helping to improve safety implementation. The statistical analyses also reveal that small, medium, and large food companies hold similar opinions on the risk factor, but bear different perceptions on the other 4 factors. It is also found that to improve safety implementation, the perceptions of safety goals, communication, feedback, safety resources, and supervision should be aligned in small, medium, and large companies.

  10. Neurovestibular Effects of Spaceflight - Considerations for Human Safety and Performance

    NASA Astrophysics Data System (ADS)

    Groen, E.

    2012-01-01

    From orbital spaceflight we know that astronauts may suffer from sensori-motor problems during the first days in weightlessness, and again upon return to Earth. Symptoms include spatial disorientation, motion illusions, postural imbalance, and motion sickness. Symptoms are typically triggered by head movements, indicating a central role of the vestibular system. TNO research has shown that the same symptoms can be elicited by exposing subjects to hyper-gravity in a human centrifuge. This suggests that not weightlessness itself, but the change in G-load causes vestibular adaptation problems. Suborbital spaceflight will expose participants to a sequence of highly variable G-levels. Hence it can be anticipated that this will affect vestibular functioning, with potential consequences for ride comfort (passengers) and flight safety (crew). We therefore propose to invest in research on the physiological responses to G-load profiles specific for suborbital flights with the purpose to establish comfort and safety guidelines for the commercial spaceflight sector.

  11. Zoonotic helminths affecting the human eye

    PubMed Central

    2011-01-01

    Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears PMID:21429191

  12. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases.

  13. Inherent safety, ethics and human error.

    PubMed

    Papadaki, Maria

    2008-02-11

    stated. The reason this article is presented here is that I believe that often, complex accidents, similarly to insignificant ones, often demonstrate an attitude which can be characterized as "inherently unsafe". I take the view that the enormous human potential and the human ability to minimize accidents needs to become a focal point towards inherent safety. Restricting ourselves to human limitations and how we could "treat" or prevent humans from not making accidents needs to be re-addressed. The purpose of this presentation is to highlight observations and provoke a discussion on how we could possibly improve the understanding of safety related issues. I do not intent to reject or criticize existing methodologies. (The entire presentation is strongly influenced by Trevor Kletz's work although our views are often different.).

  14. Parameters affecting of Akkuyu's safety assessment for severe core damages

    NASA Astrophysics Data System (ADS)

    Kavun, Yusuf; Karasulu, Muzaffer

    2015-07-01

    We have looked at all past core meltdowns (Three Mile Island, Chernobyl and Fukushima incidents) and postulated the fourth one might be taking place in the future most probably in a newly built reactors anywhere of the earth in any type of NPP. The probability of this observation is high considering the nature of the machine and human interaction. Operation experience is a very significant parameter as well as the safety culture of the host nation. The concerns is not just a lack of experience with industry with the new comers, but also the infrastructure and established institutions who will be dealing with the Emergencies. Lack of trained and educated Emergency Response Organizations (ERO) is a major concern. The culture on simple fire drills even makes the difference when a severe condition occurs in the industry. The study assumes the fourth event will be taking place at the Akkuyu NGS and works backwards as required by the "what went wrong " scenarios and comes up with interesting results. The differences studied in depth to determine the impact to the severe accidents. The all four design have now core catchers. We have looked at the operator errors'like in TMI); Operator errors combined with design deficiencies(like in Chernobyl) and natural disasters( like in Fukushima) and found operator errors to be more probable event on the Akkuyu's postulated next incident. With respect to experiences of the operators we do not have any data except for long and successful operating history of the Soviet design reactors up until the Chernobyl incident. Since the Akkuyu will be built, own and operated by the Russians we have found no alarming concerns at the moment. At the moment, there is no body be able to operate those units in Turkey. Turkey is planning to build the required manpower during the transition period. The resolution of the observed parameters lies to work and educate, train of the host nation and exercise together.

  15. Human Hallucinogen Research: Guidelines for Safety

    PubMed Central

    Johnson, Matthew W.; Richards, William A.; Griffiths, Roland R.

    2010-01-01

    There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (“bad trip”), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment, and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. PMID:18593734

  16. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  17. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  18. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  19. Human factors systems approach to healthcare quality and patient safety

    PubMed Central

    Carayon, Pascale; Wetterneck, Tosha B.; Rivera-Rodriguez, A. Joy; Hundt, Ann Schoofs; Hoonakker, Peter; Holden, Richard; Gurses, Ayse P.

    2013-01-01

    Human factors systems approaches are critical for improving healthcare quality and patient safety. The SEIPS (Systems Engineering Initiative for Patient Safety) model of work system and patient safety is a human factors systems approach that has been successfully applied in healthcare research and practice. Several research and practical applications of the SEIPS model are described. Important implications of the SEIPS model for healthcare system and process redesign are highlighted. Principles for redesigning healthcare systems using the SEIPS model are described. Balancing the work system and encouraging the active and adaptive role of workers are key principles for improving healthcare quality and patient safety. PMID:23845724

  20. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Other Federal agency standards affecting occupational safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other...

  1. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Other Federal agency standards affecting occupational safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other...

  2. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Other Federal agency standards affecting occupational safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other...

  3. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Other Federal agency standards affecting occupational safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other...

  4. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Other Federal agency standards affecting occupational safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other...

  5. Health and safety and the Human Rights Act 1998.

    PubMed

    Tearle, P

    2001-03-01

    The Human Rights Act 1998 came into effect on 2 October 2000. The list of human rights now embodied in United Kingdom law reflects the ideas and values of our changing and developing society. As a dynamic document the act has parallels with the ideals found in health and safety law. This article looks at the act and considers its implications for employers with regard to existing health and safety law.

  6. An Empirical Analysis of Human Performance and Nuclear Safety Culture

    SciTech Connect

    Jeffrey Joe; Larry G. Blackwood

    2006-06-01

    The purpose of this analysis, which was conducted for the US Nuclear Regulatory Commission (NRC), was to test whether an empirical connection exists between human performance and nuclear power plant safety culture. This was accomplished through analyzing the relationship between a measure of human performance and a plant’s Safety Conscious Work Environment (SCWE). SCWE is an important component of safety culture the NRC has developed, but it is not synonymous with it. SCWE is an environment in which employees are encouraged to raise safety concerns both to their own management and to the NRC without fear of harassment, intimidation, retaliation, or discrimination. Because the relationship between human performance and allegations is intuitively reciprocal and both relationship directions need exploration, two series of analyses were performed. First, human performance data could be indicative of safety culture, so regression analyses were performed using human performance data to predict SCWE. It also is likely that safety culture contributes to human performance issues at a plant, so a second set of regressions were performed using allegations to predict HFIS results.

  7. Space station crew safety alternatives study. Volume 3: Safety impact of human factors

    NASA Technical Reports Server (NTRS)

    Rockoff, L. A.; Raasch, R. F.; Peercy, R. L., Jr.

    1985-01-01

    The first 15 years of accumulated space station concepts for Initial Operational Capability (IOC) during the early 1990's was considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris. Of particular interest here is volume three (of five volumes) pertaining to the safety impact of human factors.

  8. Fall protection characteristics of safety belts and human impact tolerance.

    PubMed

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-01-01

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt, which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness, which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

  9. Safety assessment of probiotics for human use

    PubMed Central

    Akkermans, Louis MA; Haller, Dirk; Hammerman, Cathy; Heimbach, James; Hörmannsperger, Gabriele; Huys, Geert; Levy, Dan D; Lutgendorff, Femke; Mack, David; Phothirath, Phoukham; Solano-Aguilar, Gloria; Vaughan, Elaine

    2010-01-01

    The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety contrasted with the long history of safe use of many of these microbes in foods. PMID:21327023

  10. New Safety Model for the Commercial Human Spaceflight Industry

    NASA Astrophysics Data System (ADS)

    Quinn, A.; Bond, S.; Maropoulos, P.

    2012-01-01

    The aviation and space domains have safety guidelines and recommended practices for Design Organisations (DOs) and Operators alike. In terms of Aerospace DOs there are certification criteria to meet and to demonstrate compliance there are Advisory Circulars or Acceptable Means of Compliance to follow. Additionally there are guidelines such as Aerospace Recommended Practices (ARP), Military Standards (MIL-STD 882 series) and System Safety Handbooks to follow in order to identify and manage failure conditions. In terms of Operators there are FAA guidelines and a useful ARP that details many tools and techniques in understanding Operator Safety Risks. However there is currently no methodology for linking the DO and Operator safety efforts. In the space domain NASA have provided safety standards and guidelines to follow and also within Europe there are European Co-operation of Space Standardization (ECSS) to follow. Within the emerging Commercial Human Spaceflight Industry, the FAA's Office of Commercial Space Transportation has provided hazard analysis guidelines. However all of these space domain safety documents are based on the existing aerospace methodology and once again, there is no link between the DO and Operator's safety effort. This paper addresses the problematic issue and presents a coherent methodology of joining up the System Safety effort of the DOs to the Operator Safety Risk Management such that a 'Total System' approach is adopted. Part of the rationale is that the correct mitigation (control) can be applied within the correct place in the accident sequence. Also this contiguous approach ensures that the Operator is fully aware of the safety risks (at the accident level) and therefore has an appreciation of the Total System Risk. The authors of this paper contend that it is better practice to have a fully integrated safety model as opposed to disparate requirements or guidelines. Our methodology is firstly to review 'best practice' approaches from

  11. Infrasound from Wind Turbines Could Affect Humans

    ERIC Educational Resources Information Center

    Salt, Alec N.; Kaltenbach, James A.

    2011-01-01

    Wind turbines generate low-frequency sounds that affect the ear. The ear is superficially similar to a microphone, converting mechanical sound waves into electrical signals, but does this by complex physiologic processes. Serious misconceptions about low-frequency sound and the ear have resulted from a failure to consider in detail how the ear…

  12. Does Globalization Affect Human Well-Being?

    ERIC Educational Resources Information Center

    Tsai, Ming-Chang

    2007-01-01

    The prevailing theorizing of globalization's influence of human well-being suggests to assess both the favorable and unfavorable outcomes. This study formulates a dialectical model, adopts a comprehensive globalization measure and uses a three-wave panel data during 1980-2000 to empirically test direct and indirect effects of global flows' human…

  13. Human Factors Research and Nuclear Safety.

    ERIC Educational Resources Information Center

    Moray, Neville P., Ed.; Huey, Beverly M., Ed.

    The Panel on Human Factors Research Needs in Nuclear Regulatory Research was formed by the National Research Council in response to a request from the Nuclear Regulatory Commission (NRC). The NRC asked the research council to conduct an 18-month study of human factors research needs for the safe operation of nuclear power plants. This report…

  14. Parameters affecting greywater quality and its safety for reuse.

    PubMed

    Maimon, Adi; Friedler, Eran; Gross, Amit

    2014-07-15

    Reusing greywater (GW) for on-site irrigation is becoming a common practice worldwide. Alongside its benefits, GW reuse might pose health and environmental risks. The current study assesses the risks associated with on-site GW reuse and the main factors affecting them. GW from 34 households in Israel was analyzed for physicochemical parameters, Escherichia coli (as an indicator for rotavirus), Pseudomonas aeruginosa and Staphylococcus aureus. Each participating household filled out a questionnaire about their GW sources, treatment and usages. Quantitative microbial risk assessment (QMRA) was performed based on the measured microbial quality, and on exposure scenarios derived from the questionnaires and literature data. The type of treatment was found to have a significant effect on the quality of the treated GW. The average E. coli counts in GW (which exclude kitchen effluent) treated by professionally-designed system resulted in acceptable risk under all exposure scenarios while the risk from inadequately-treated GW was above the accepted level as set by the WHO. In conclusion, safe GW reuse requires a suitable and well-designed treatment system. A risk-assessment approach should be used to adjust the current regulations/guidelines and to assess the performance of GW treatment and reuse systems.

  15. Plant sterols: factors affecting their efficacy and safety as functional food ingredients

    PubMed Central

    Berger, Alvin; Jones, Peter JH; Abumweis, Suhad S

    2004-01-01

    Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status. PMID:15070410

  16. Targeting of blood safety measures to affected areas with ongoing local transmission of malaria.

    PubMed

    Domanović, D; Kitchen, A; Politis, C; Panagiotopoulos, T; Bluemel, J; Van Bortel, W; Overbosch, D; Lieshout-Krikke, R; Fabra, C; Facco, G; Zeller, H

    2016-06-01

    An outbreak of locally acquired Plasmodium vivax malaria in Greece started in 2009 and peaked in 2011. Targeting of blood safety measures to affected areas with ongoing transmission of malaria raised questions of how to define spatial boundaries of such an area and when to trigger any specific blood safety measures, including whether and which blood donation screening strategy to apply. To provide scientific advice the European Centre for Disease Prevention and Control (ECDC) organised expert meetings in 2013. The outcomes of these consultations are expert opinions covering spatial targeting of blood safety measures to affected areas with ongoing local transmission of malaria and blood donation screening strategy for evidence of malaria infection in these areas. Opinions could help EU national blood safety authorities in developing a preventive strategy during malaria outbreaks. PMID:27238883

  17. Evaluating Models of Human Performance: Safety-Critical Systems Applications

    NASA Technical Reports Server (NTRS)

    Feary, Michael S.

    2012-01-01

    This presentation is part of panel discussion on Evaluating Models of Human Performance. The purpose of this panel is to discuss the increasing use of models in the world today and specifically focus on how to describe and evaluate models of human performance. My presentation will focus on discussions of generating distributions of performance, and the evaluation of different strategies for humans performing tasks with mixed initiative (Human-Automation) systems. I will also discuss issues with how to provide Human Performance modeling data to support decisions on acceptability and tradeoffs in the design of safety critical systems. I will conclude with challenges for the future.

  18. Maggot excretions affect the human complement system.

    PubMed

    Cazander, Gwendolyn; Schreurs, Marco W J; Renwarin, Lennaert; Dorresteijn, Corry; Hamann, Dörte; Jukema, Gerrolt N

    2012-01-01

    The complement system plays an important role in the activation of the inflammatory response to injury, although inappropriate complement activation (CA) can lead to severe tissue damage. Maggot therapy is successfully used to treat infected wounds. In this study, we hypothesized that maggot excretions/secretions influence CA in order to modulate the host's inflammatory response. Therefore, the effect of maggot excretions on CA was investigated in preoperatively and postoperatively obtained sera from patients. Our results show that maggot excretions reduce CA in healthy and postoperatively immune-activated human sera up to 99.9%, via all pathways. Maggot excretions do not specifically initiate or inhibit CA, but break down complement proteins C3 and C4 in a cation-independent manner and this effect proves to be temperature tolerant. This study indicates a CA-reducing substrate that is already successfully used in clinical practice and may explain part of the improved wound healing caused by maggot therapy. Furthermore, the complement activation-reducing substance present in maggot excretions could provide a novel treatment modality for several diseases, resulting from an (over)active complement system.

  19. Electrical Safety for Human Space Flight Payload Hardware

    NASA Astrophysics Data System (ADS)

    Runnells, James A.

    2010-09-01

    Human Space Flight payload hardware designs must address both mission success and safety requirements for flight on the Space Shuttle, International Space Station(ISS), or International Partner(IP) Launch Vehicles. Flight hardware generally can be considered either Government Furnished Equipment(GFE) or Payload hardware, although some Commercial-off-the-shelf(COTS) hardware is also flown. In this case we will use the payload flight hardware system safety perspective, which closely resembles the GFE system safety process with a few exceptions. Why is Human space flight hardware treated differently than ground hardware? The key reason flight hardware is treated more conservatively than ground hardware is the relative impact to crew and vehicle, and the relative inability to provide immediate recovery of a disabled space vehicle or crewmember on-orbit. One aspect of safe payload flight hardware design is Electrical Power Systems(EPS), including the safe design and operations of electrical power systems for payloads.

  20. Toward an Affective Pedagogy of Human Rights Education

    ERIC Educational Resources Information Center

    Hung, Ruyu

    2014-01-01

    This paper explores the notion of Affective Pedagogy of Human Rights Education (APHRE) on a theoretical level and suggests a concept of curricular framework. APHRE highlights the significance of affectivity and body in the process of learning, factors usually neglected in the mainstream intellectualistic approach to learning, especially in areas…

  1. Food safety. [chemical contaminants and human toxic diseases

    NASA Technical Reports Server (NTRS)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  2. Safety Metrics for Human-Computer Controlled Systems

    NASA Technical Reports Server (NTRS)

    Leveson, Nancy G; 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.

  3. Human safety and efficacy of ultraviolet filters and sunscreen products.

    PubMed

    Nash, J F

    2006-01-01

    Ultraviolet (UV) filters are the active ingredients in sunscreens. The concentration and combination of UV filters determine the efficacy of sunscreens as measured by sun protection factor. The safety of individual UV filters, and, more generally, sunscreen products, is a matter of a few related components: objective toxicologic evaluation, phototoxicologic potential, and human health consequences of using products that may reduce some but not all of the solar UV. Of 16 UV filters approved by the US Food and Drug Administration, 9 are used in different combinations in the most currently marketed sunscreens. Most of these compounds are considered safe and effective alone or in combination with other UV filters based on extensive toxicologic/phototoxicologic evaluations and market history. The benefits from proper use of sunscreens outweigh real or perceived human health concerns, establishing a favorable benefit-to-risk ratio. Future UV filters will require complete human safety evaluations alone and in combination with select benchmark ingredients.

  4. Spacecraft Fire Safety: A Human Space Flight Program Perspective

    NASA Technical Reports Server (NTRS)

    Pedley, Michael D.

    2003-01-01

    This paper presents viewgraphs on the International Space Station's fire safety program from a human space flight perspective. The topics include: 1) Typical Manned Spacecraft Materials; 2) Typical Flammable Hardware Protection; 3) Materials Flammability; 4) Fire Retardants; 5) Nonflammable Foam Cushion Material; 6) Electrical Wire and Cable; 7) Russian Solid-Fuel Oxygen Generator (SFOG); 8) GOX Ignition Mechanisms; 9) Fire Detection; and 10) Fire Suppression.

  5. Direct Human Contact with Siloxanes (Silicones) – Safety or Risk Part 1. Characteristics of Siloxanes (Silicones)

    PubMed Central

    Mojsiewicz-Pieńkowska, Krystyna; Jamrógiewicz, Marzena; Szymkowska, Katarzyna; Krenczkowska, Dominika

    2016-01-01

    Siloxanes are commonly known as silicones. They belong to the organosilicon compounds and are exclusively obtained by synthesis. Their chemical structure determines a range of physicochemical properties which were recognized as unique. Due to the susceptibility to chemical modifications, ability to create short, long or complex polymer particles, siloxanes found an application in many areas of human life. Siloxanes differ in particle size, molecular weight, shape and chemical groups. As a result, this determines the different physico-chemical properties, that directly affect the safety or the risk of their use. The areas that can be a source of danger to human health will be commented in this paper. PMID:27303296

  6. How Do Volcanoes Affect Human Life? Integrated Unit.

    ERIC Educational Resources Information Center

    Dayton, Rebecca; Edwards, Carrie; Sisler, Michelle

    This packet contains a unit on teaching about volcanoes. The following question is addressed: How do volcanoes affect human life? The unit covers approximately three weeks of instruction and strives to present volcanoes in an holistic form. The five subject areas of art, language arts, mathematics, science, and social studies are integrated into…

  7. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Safety: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... Regulations to address human factors and other aspects of control room management for pipelines where... 63310) entitled ``Pipeline Safety: Control Room Management/Human Factors.'' This final rule...

  8. Alaska Humans Factors Safety Study: The Southern Coastal Area

    NASA Technical Reports Server (NTRS)

    Chappell, Sheryl L.; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASA-ASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the southern coastal areas, specifically: Anchorage, Dillingham, King Salmon, Kodiak, Cold Bay, Juneau, and Ketchikan. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  9. Alaska Humans Factors Safety Study: The Northern Area

    NASA Technical Reports Server (NTRS)

    Connell, Linda; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASAASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the northern area, specifically: Bethel, Fairbanks, Nome, Kotzebue, and Barrow. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  10. Incorporating affective bias in models of human decision making

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1991-01-01

    Research on human decision making has traditionally focused on how people actually make decisions, how good their decisions are, and how their decisions can be improved. Recent research suggests that this model is inadequate. Affective as well as cognitive components drive the way information about relevant outcomes and events is perceived, integrated, and used in the decision making process. The affective components include how the individual frames outcomes as good or bad, whether the individual anticipates regret in a decision situation, the affective mood state of the individual, and the psychological stress level anticipated or experienced in the decision situation. A focus of the current work has been to propose empirical studies that will attempt to examine in more detail the relationships between the latter two critical affective influences (mood state and stress) on decision making behavior.

  11. The effects of physical environments in medical wards on medication communication processes affecting patient safety.

    PubMed

    Liu, Wei; Manias, Elizabeth; Gerdtz, Marie

    2014-03-01

    Physical environments of clinical settings play an important role in health communication processes. Effective medication management requires seamless communication among health professionals of different disciplines. This paper explores how physical environments affect communication processes for managing medications and patient safety in acute care hospital settings. Findings highlighted the impact of environmental interruptions on communication processes about medications. In response to frequent interruptions and limited space within working environments, nurses, doctors and pharmacists developed adaptive practices in the local clinical context. Communication difficulties were associated with the ward physical layout, the controlled drug key and the medication retrieving device. Health professionals should be provided with opportunities to discuss the effects of ward environments on medication communication processes and how this impacts medication safety. Hospital administrators and architects need to consider health professionals' views and experiences when designing hospital spaces. PMID:24486620

  12. Quality and safety aspects of meat products as affected by various physical manipulations of packaging materials.

    PubMed

    Lee, Keun Taik

    2010-09-01

    This article explores the effects of physically manipulated packaging materials on the quality and safety of meat products. Recently, innovative measures for improving quality and extending the shelf-life of packaged meat products have been developed, utilizing technologies including barrier film, active packaging, nanotechnology, microperforation, irradiation, plasma and far-infrared ray (FIR) treatments. Despite these developments, each technology has peculiar drawbacks which will need to be addressed by meat scientists in the future. To develop successful meat packaging systems, key product characteristics affecting stability, environmental conditions during storage until consumption, and consumers' packaging expectations must all be taken into consideration. Furthermore, the safety issues related to packaging materials must also be taken into account when processing, packaging and storing meat products.

  13. The effects of physical environments in medical wards on medication communication processes affecting patient safety.

    PubMed

    Liu, Wei; Manias, Elizabeth; Gerdtz, Marie

    2014-03-01

    Physical environments of clinical settings play an important role in health communication processes. Effective medication management requires seamless communication among health professionals of different disciplines. This paper explores how physical environments affect communication processes for managing medications and patient safety in acute care hospital settings. Findings highlighted the impact of environmental interruptions on communication processes about medications. In response to frequent interruptions and limited space within working environments, nurses, doctors and pharmacists developed adaptive practices in the local clinical context. Communication difficulties were associated with the ward physical layout, the controlled drug key and the medication retrieving device. Health professionals should be provided with opportunities to discuss the effects of ward environments on medication communication processes and how this impacts medication safety. Hospital administrators and architects need to consider health professionals' views and experiences when designing hospital spaces.

  14. Positive Affect and the Complex Dynamics of Human Flourishing

    PubMed Central

    Fredrickson, Barbara L.; Losada, Marcial F.

    2011-01-01

    Extending B. L. Fredrickson’s (1998) broaden-and-build theory of positive emotions and M. Losada’s (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N = 188) completed an initial survey to identify flourishing mental health and then provided daily reports of experienced positive and negative emotions over 28 days. Results showed that the mean ratio of positive to negative affect was above 2.9 for individuals classified as flourishing and below that threshold for those not flourishing. Together with other evidence, these findings suggest that a set of general mathematical principles may describe the relations between positive affect and human flourishing. PMID:16221001

  15. Positive affect and the complex dynamics of human flourishing.

    PubMed

    Fredrickson, Barbara L; Losada, Marcial F

    2005-10-01

    Extending B. L. Fredrickson's (1998) broaden-and-build theory of positive emotions and M. Losada's (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N=188) completed an initial survey to identify flourishing mental health and then provided daily reports of experienced positive and negative emotions over 28 days. Results showed that the mean ratio of positive to negative affect was above 2.9 for individuals classified as flourishing and below that threshold for those not flourishing. Together with other evidence, these findings suggest that a set of general mathematical principles may describe the relations between positive affect and human flourishing. PMID:16221001

  16. The safety of human pluripotent stem cells in clinical treatment.

    PubMed

    Simonson, Oscar E; Domogatskaya, Anna; Volchkov, Pavel; Rodin, Sergey

    2015-01-01

    Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments.

  17. The safety of human pluripotent stem cells in clinical treatment.

    PubMed

    Simonson, Oscar E; Domogatskaya, Anna; Volchkov, Pavel; Rodin, Sergey

    2015-01-01

    Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments. PMID:26140342

  18. The Safety of Cruciferous Plants in Humans: A Systematic Review

    PubMed Central

    Scott, Ori; Galicia-Connolly, Elaine; Adams, Denise; Surette, Soleil; Vohra, Sunita; Yager, Jerome Y.

    2012-01-01

    Some cruciferous plants may serve as preventive treatments for several medical conditions; our objective was to systematically investigate their safety in humans. Four electronic databases were searched, and, of 10,831 references identified, 50 were included. Data were extracted by two independent reviewers, whereafter the association between interventions and adverse events was assessed. Adverse events in 53 subjects were identified through clinical trials; of these, altered drug metabolism was rated as certainly/likely caused by cruciferous plants. Adverse events in 1247 subjects were identified through observational studies, of which none received high causality ratings. Adverse events in 35 subjects were identified through case reports, of which allergies and warfarin resistance were rated as certainly/likely caused by cruciferous plants. We conclude that cruciferous plants are safe in humans, with the exception of allergies. Individuals treated with warfarin should consult their physician. Further investigation of uses of cruciferous plants in preventative medicine is warranted. PMID:22500092

  19. Efficacy and Safety of Human Retinal Progenitor Cells

    PubMed Central

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  20. Affect is central to patient safety: the horror stories of young anaesthetists.

    PubMed

    Iedema, Rick; Jorm, Christine; Lum, Martin

    2009-12-01

    This paper analyses talk produced by twenty-four newly qualified anaesthetists. Data were collected from round table discussions at the Young Fellows Conference of the Australia and New Zealand College of Anaesthetists 2006. The talk consisted to an important extent of narratives about experiences of horror. The paper isolates three themes: the normalization of horror, the functionalisation of horror for pedagogic purposes, and the problematization of horror. The last theme provides a springboard into our argument that confronting the affect invested in coping with medical-clinical failure is central to enabling young doctors, and clinicians generally, to address and resolve such adverse events. We conclude that the negotiation of affect through shared or 'dialogic' narrative is central to enabling doctors to deal with adverse events on a personal level, and to enabling them at a collective level to become attentive to threats to patients' safety.

  1. Affect is central to patient safety: the horror stories of young anaesthetists.

    PubMed

    Iedema, Rick; Jorm, Christine; Lum, Martin

    2009-12-01

    This paper analyses talk produced by twenty-four newly qualified anaesthetists. Data were collected from round table discussions at the Young Fellows Conference of the Australia and New Zealand College of Anaesthetists 2006. The talk consisted to an important extent of narratives about experiences of horror. The paper isolates three themes: the normalization of horror, the functionalisation of horror for pedagogic purposes, and the problematization of horror. The last theme provides a springboard into our argument that confronting the affect invested in coping with medical-clinical failure is central to enabling young doctors, and clinicians generally, to address and resolve such adverse events. We conclude that the negotiation of affect through shared or 'dialogic' narrative is central to enabling doctors to deal with adverse events on a personal level, and to enabling them at a collective level to become attentive to threats to patients' safety. PMID:19846244

  2. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

    PubMed Central

    Schoedel, Kerri A; Morrow, Sarah A; Sellers, Edward M

    2014-01-01

    Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients

  3. Human likeness: cognitive and affective factors affecting adoption of robot-assisted learning systems

    NASA Astrophysics Data System (ADS)

    Yoo, Hosun; Kwon, Ohbyung; Lee, Namyeon

    2016-07-01

    With advances in robot technology, interest in robotic e-learning systems has increased. In some laboratories, experiments are being conducted with humanoid robots as artificial tutors because of their likeness to humans, the rich possibilities of using this type of media, and the multimodal interaction capabilities of these robots. The robot-assisted learning system, a special type of e-learning system, aims to increase the learner's concentration, pleasure, and learning performance dramatically. However, very few empirical studies have examined the effect on learning performance of incorporating humanoid robot technology into e-learning systems or people's willingness to accept or adopt robot-assisted learning systems. In particular, human likeness, the essential characteristic of humanoid robots as compared with conventional e-learning systems, has not been discussed in a theoretical context. Hence, the purpose of this study is to propose a theoretical model to explain the process of adoption of robot-assisted learning systems. In the proposed model, human likeness is conceptualized as a combination of media richness, multimodal interaction capabilities, and para-social relationships; these factors are considered as possible determinants of the degree to which human cognition and affection are related to the adoption of robot-assisted learning systems.

  4. Global water resources affected by human interventions and climate change

    PubMed Central

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D.; Wada, Yoshihide; Wisser, Dominik

    2014-01-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future. PMID:24344275

  5. Global water resources affected by human interventions and climate change.

    PubMed

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D; Wada, Yoshihide; Wisser, Dominik

    2014-03-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future.

  6. 75 FR 69912 - Pipeline Safety: Control Room Management/Human Factors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... Safety: Control Room Management/Human Factors AGENCY: Pipeline and Hazardous Materials Safety..., 2010, PHMSA published a Control Room Management/Human Factors notice of proposed rulemaking (NPRM... to expedite the program implementation deadlines of the Control Room Management/Human Factors rule...

  7. Human Factors And Safety Considerations Of Night Vision Systems Flight

    NASA Astrophysics Data System (ADS)

    Verona, Robert W.; Rash, Clarence E.

    1989-03-01

    Military aviation night vision systems greatly enhance the capability to operate during periods of low illumination. After flying with night vision devices, most aviators are apprehensive about returning to unaided night flight. Current night vision imaging devices allow aviators to fly during ambient light conditions which would be extremely dangerous, if not impossible, with unaided vision. However, the visual input afforded with these devices does not approach that experienced using the unencumbered, unaided eye during periods of daylight illumination. Many visual parameters, e,g., acuity, field-of-view, depth perception, etc., are compromised when night vision devices are used. The inherent characteristics of image intensification based sensors introduce new problems associated with the interpretation of visual information based on different spatial and spectral content from that of unaided vision. In addition, the mounting of these devices onto the helmet is accompanied by concerns of fatigue resulting from increased head supported weight and shift in center-of-gravity. All of these concerns have produced numerous human factors and safety issues relating to thb use of night vision systems. These issues are identified and discussed in terms of their possible effects on user performance and safety.

  8. Human teratogens update 2011: can we ensure safety during pregnancy?

    PubMed

    Rasmussen, Sonja A

    2012-03-01

    Anniversaries of the identification of three human teratogens (i.e., rubella virus in 1941, thalidomide in 1961, and diethylstilbestrol in 1971) occurred in 2011. These experiences highlight the critical role that scientists with an interest in teratology play in the identification of teratogenic exposures as the basis for developing strategies for prevention of those exposures and the adverse outcomes associated with them. However, an equally important responsibility for teratologists is to evaluate whether medications and vaccines are safe for use during pregnancy so informed decisions about disease treatment and prevention during pregnancy can be made. Several recent studies have examined the safety of medications during pregnancy, including antiviral medications used to treat herpes simplex and zoster, proton pump inhibitors used to treat gastroesophageal reflux, and newer-generation antiepileptic medications used to treat seizures and other conditions. Despite the large numbers of pregnant women included in these studies and the relatively reassuring results, the question of whether these medications are teratogens remains. In addition, certain vaccines are recommended during pregnancy to prevent infections in mothers and infants, but clinical trials to test these vaccines typically exclude pregnant women; thus, evaluation of their safety depends on observational studies. For pregnant women to receive optimal care, we need to define the data needed to determine whether a medication or vaccine is "safe" for use during pregnancy. In the absence of adequate, well-controlled data, it will often be necessary to weigh the benefits of medications or vaccines with potential risks to the embryo or fetus.

  9. [Development of human embryonic stem cell platforms for human health-safety evaluation].

    PubMed

    Yu, Guang-yan; Cao, Tong; Zou, Xiao-hui; Zhang, Xue-hui; Fu, Xin; Peng, Shuang-qing; Deng, Xu-liang; Li, Sheng-lin; Liu, He; Xiao, Ran; Ouyang, Hong-wei; Peng, Hui; Chen, Xiao; Zhao, Zeng-ming; Wang, Xiao-ying; Fang, Hai-qin; Lu, Lu; Ren, Yu-lan; Xu, Ming-ming

    2016-02-18

    The human embryonic stem cells (hESCs) serve as a self-renewable, genetically-healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A-biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts. The evaluations were compared with those on the currently most adopted cellular platforms. Particularly, the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endothelial cells (HUVECs) were evaluated. The RESULTS showed that the standardized hESCs cellular platforms provided more sensitivity and accuracy for human cellular health-safety evaluation. PMID:26885900

  10. Affective consciousness: Core emotional feelings in animals and humans.

    PubMed

    Panksepp, Jaak

    2005-03-01

    The position advanced in this paper is that the bedrock of emotional feelings is contained within the evolved emotional action apparatus of mammalian brains. This dual-aspect monism approach to brain-mind functions, which asserts that emotional feelings may reflect the neurodynamics of brain systems that generate instinctual emotional behaviors, saves us from various conceptual conundrums. In coarse form, primary process affective consciousness seems to be fundamentally an unconditional "gift of nature" rather than an acquired skill, even though those systems facilitate skill acquisition via various felt reinforcements. Affective consciousness, being a comparatively intrinsic function of the brain, shared homologously by all mammalian species, should be the easiest variant of consciousness to study in animals. This is not to deny that some secondary processes (e.g., awareness of feelings in the generation of behavioral choices) cannot be evaluated in animals with sufficiently clever behavioral learning procedures, as with place-preference procedures and the analysis of changes in learned behaviors after one has induced re-valuation of incentives. Rather, the claim is that a direct neuroscientific study of primary process emotional/affective states is best achieved through the study of the intrinsic ("instinctual"), albeit experientially refined, emotional action tendencies of other animals. In this view, core emotional feelings may reflect the neurodynamic attractor landscapes of a variety of extended trans-diencephalic, limbic emotional action systems-including SEEKING, FEAR, RAGE, LUST, CARE, PANIC, and PLAY. Through a study of these brain systems, the neural infrastructure of human and animal affective consciousness may be revealed. Emotional feelings are instantiated in large-scale neurodynamics that can be most effectively monitored via the ethological analysis of emotional action tendencies and the accompanying brain neurochemical/electrical changes. The

  11. The Development of Dynamic Human Reliability Analysis Simulations for Inclusion in Risk Informed Safety Margin Characterization Frameworks

    SciTech Connect

    Jeffrey C. Joe; Diego Mandelli; Ronald L. Boring; Curtis L. Smith; Rachel B. Shirley

    2015-07-01

    The United States Department of Energy is sponsoring the Light Water Reactor Sustainability program, which has the overall objective of supporting the near-term and the extended operation of commercial nuclear power plants. One key research and development (R&D) area in this program is the Risk-Informed Safety Margin Characterization pathway, which combines probabilistic risk simulation with thermohydraulic simulation codes to define and manage safety margins. The R&D efforts to date, however, have not included robust simulations of human operators, and how the reliability of human performance or lack thereof (i.e., human errors) can affect risk-margins and plant performance. This paper describes current and planned research efforts to address the absence of robust human reliability simulations and thereby increase the fidelity of simulated accident scenarios.

  12. 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

  13. Human health and safety risks management in underground coal mines using fuzzy TOPSIS.

    PubMed

    Mahdevari, Satar; Shahriar, Kourosh; Esfahanipour, Akbar

    2014-08-01

    The scrutiny of health and safety of personnel working in underground coal mines is heightened because of fatalities and disasters that occur every year worldwide. A methodology based on fuzzy TOPSIS was proposed to assess the risks associated with human health in order to manage control measures and support decision-making, which could provide the right balance between different concerns, such as safety and costs. For this purpose, information collected from three hazardous coal mines namely Hashouni, Hojedk and Babnizu located at the Kerman coal deposit, Iran, were used to manage the risks affecting the health and safety of their miners. Altogether 86 hazards were identified and classified under eight categories: geomechanical, geochemical, electrical, mechanical, chemical, environmental, personal, and social, cultural and managerial risks. Overcoming the uncertainty of qualitative data, the ranking process is accomplished by fuzzy TOPSIS. After running the model, twelve groups with different risks were obtained. Located in the first group, the most important risks with the highest negative effects are: materials falling, catastrophic failure, instability of coalface and immediate roof, firedamp explosion, gas emission, misfire, stopping of ventilation system, wagon separation at inclines, asphyxiation, inadequate training and poor site management system. According to the results, the proposed methodology can be a reliable technique for management of the minatory hazards and coping with uncertainties affecting the health and safety of miners when performance ratings are imprecise. The proposed model can be primarily designed to identify potential hazards and help in taking appropriate measures to minimize or remove the risks before accidents can occur.

  14. Common problems in the elicitation and analysis of expert opinion affecting probabilistic safety assessments

    SciTech Connect

    Meyer, M.A.; Booker, J.M.

    1990-01-01

    Expert opinion is frequently used in probabilistic safety assessment (PSA), particularly in estimating low probability events. In this paper, we discuss some of the common problems encountered in eliciting and analyzing expert opinion data and offer solutions or recommendations. The problems are: that experts are not naturally Bayesian. People fail to update their existing information to account for new information as it becomes available, as would be predicted by the Bayesian philosophy; that experts cannot be fully calibrated. To calibrate experts, the feedback from the known quantities must be immediate, frequent, and specific to the task; that experts are limited in the number of things that they can mentally juggle at a time to 7 {plus minus} 2; that data gatherers and analysts can introduce bias by unintentionally causing an altering of the expert's thinking or answers; that the level of detail the data, or granularity, can affect the analyses; and the conditioning effect poses difficulties in gathering and analyzing of the expert data. The data that the expert gives can be conditioned on a variety of factors that can affect the analysis and the interpretation of the results. 31 refs.

  15. Metformin selectively affects human glioblastoma tumor-initiating cell viability

    PubMed Central

    Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2013-01-01

    Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

  16. Environmental layout complexity affects neural activity during navigation in humans.

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.

  17. Environmental layout complexity affects neural activity during navigation in humans.

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. PMID:26990572

  18. Do ELF magnetic fields affect human reaction time?

    SciTech Connect

    Podd, J.V.; Whittington, C.J.; Barnes, G.R.G.; Page, W.H.; Rapley, B.I.

    1995-12-01

    Two double-blind studies were run in an attempt to confirm the finding that a 0.2 Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz field does not. In the first experiment, 12 volunteer subjects were exposed to a continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counter-balanced, within-subjects design. Subjects were run singly for one condition each day over 3 consecutive days with a field strength of 1.1 mT and a daily expose duration of 5 min. Neither magnetic field had any effect on RT at any time during the exposure. One condition of a second study, using a new group of 24 volunteer subjects, also failed to find any field effects at 0.2 Hz. Additionally, the second study failed to show any effects when the frequency, flux density, and field orientation were set according to parameter resonance theory. It is suggested that, although ELF magnetic field effects on human behavior may be elusive, future research can improve detection rates by paying greater attention to reducing error variance and increasing statistical power.

  19. Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

    PubMed Central

    Panksepp, Jaak

    2011-01-01

    Background The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. Principal Findings The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher

  20. Time to accelerate integration of human factors and ergonomics in patient safety.

    PubMed

    Gurses, Ayse P; Ozok, A Ant; Pronovost, Peter J

    2012-04-01

    Progress toward improving patient safety has been slow despite engagement of the health care community in improvement efforts. A potential reason for this sluggish pace is the inadequate integration of human factors and ergonomics principles and methods in these efforts. Patient safety problems are complex and rarely caused by one factor or component of a work system. Thus, health care would benefit from human factors and ergonomics evaluations to systematically identify the problems, prioritize the right ones, and develop effective and practical solutions. This paper gives an overview of the discipline of human factors and ergonomics and describes its role in improving patient safety. We provide examples of how human factors and ergonomics principles and methods have improved both care processes and patient outcomes. We provide five major recommendations to better integrate human factors and ergonomics in patient safety improvement efforts: build capacity among health care workers to understand human factors and ergonomics, create market forces that demand the integration of human factors and ergonomics design principles into medical technologies, increase the number of human factors and ergonomic practitioners in health care organizations, expand investments in improvement efforts informed by human factors and ergonomics, and support interdisciplinary research to improve patient safety. In conclusion, human factors and ergonomics must play a more prominent role in health care if we want to increase the pace in improving patient safety.

  1. Affective Man-Machine Interface: Unveiling Human Emotions through Biosignals

    NASA Astrophysics Data System (ADS)

    van den Broek, Egon L.; Lisý, Viliam; Janssen, Joris H.; Westerink, Joyce H. D. M.; Schut, Marleen H.; Tuinenbreijer, Kees

    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological proce-sses, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals.

  2. Temperature Affects Human Sweet Taste via At Least Two Mechanisms.

    PubMed

    Green, Barry G; Nachtigal, Danielle

    2015-07-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5-41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5-12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2-T1R3 transduction cascade. PMID:25963040

  3. Temperature Affects Human Sweet Taste via At Least Two Mechanisms.

    PubMed

    Green, Barry G; Nachtigal, Danielle

    2015-07-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5-41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5-12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2-T1R3 transduction cascade.

  4. Copper utilization in humans as affected by amino acid supplements

    SciTech Connect

    Kies, C.; Chuang, J.H.; Fox, H.M. )

    1989-02-09

    Earlier work suggests that absorption of copper as well as several other mineral nutrients may be promoted, inhibited or unaffected by the formation of mineral-amino acid complexes. The objective of the current project was to determine effects of low level supplements of selected amino acids on copper utilization. In a series of studies, healthy, human adult subjected received a basal diet with or without test supplements in separate 14-day periods which were arranged according to a randomized, cross-over design. Test amino acids and amounts given per subject per day were as follows; L-arginine, 1.2 g; L-lysine, 1.0 g; L-cystine, 1.0 g and L-methionine, 1.0 g. Subjects made complete collections of urine and stools. Fasting blood samples were drawn. Food, urine, feces and blood were analyzed for copper contents using a carbon rod attachment on a Varian atomic absorption spectrophotometer. Fecal copper losses were unaffected by used of lysine, tryptophan and methionine supplements but were reduced with use of the arginine and cystine supplements. Urine losses of copper were reduced with used of the lysine and tryptophan supplements, were increased with the methionine and cystine supplements and were unaffected when the arginine supplements were employed. Blood serum copper levels were not significantly affected by use of these supplement although some trends were noted.

  5. Temperature Affects Human Sweet Taste via At Least Two Mechanisms

    PubMed Central

    Nachtigal, Danielle

    2015-01-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5–41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5–12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2–T1R3 transduction cascade. PMID:25963040

  6. Postmarketing safety reports for human drug and biological products; electronic submission requirements. Final rule.

    PubMed

    2014-06-10

    The Food and Drug Administration (FDA or we) is amending its postmarketing safety reporting regulations for human drug and biological products to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. FDA is taking this action to improve the Agency's systems for collecting and analyzing postmarketing safety reports. The change will help the Agency to more rapidly review postmarketing safety reports, identify emerging safety problems, and disseminate safety information in support of FDA's public health mission. In addition, the amendments will be a key element in harmonizing FDA's postmarketing safety reporting regulations with international standards for the electronic submission of safety information.

  7. Games that ''Work'': Using Computer Games to Teach Alcohol-Affected Children about Fire and Street Safety

    ERIC Educational Resources Information Center

    Coles, Claire D.; Strickland, Dorothy C.; Padgett, Lynne; Bellmoff, Lynnae

    2007-01-01

    Unintentional injuries are a leading cause of death and disability for children. Those with developmental disabilities, including children affected by prenatal alcohol exposure, are at highest risk for injuries. Although teaching safety skills is recommended to prevent injury, cognitive limitations and behavioral problems characteristic of…

  8. Do toxic heavy metals affect antioxidant defense mechanisms in humans?

    PubMed

    Wieloch, Monika; Kamiński, Piotr; Ossowska, Anna; Koim-Puchowska, Beata; Stuczyński, Tomasz; Kuligowska-Prusińska, Magdalena; Dymek, Grażyna; Mańkowska, Aneta; Odrowąż-Sypniewska, Grażyna

    2012-04-01

    The aim of this study was to prove whether anthropogenic pollution affects antioxidant defense mechanisms such as superoxide dismutase (SOD) and catalase (CAT) activity, ferritin (FRT) concentration and total antioxidant status (TAS) in human serum. The study area involves polluted and salted environment (Kujawy region; northern-middle Poland) and Tuchola Forestry (unpolluted control area). We investigated 79 blood samples of volunteers from polluted area and 82 from the control in 2008 and 2009. Lead, cadmium and iron concentrations were measured in whole blood by the ICP-MS method. SOD and CAT activities were measured in serum using SOD and CAT Assay Kits by the standardized colorimetric method. Serum TAS was measured spectrophotometrically by the modified Benzie and Strain (1996) method and FRT concentration-by the immunonefelometric method. Pb and Cd levels and SOD activity were higher in volunteers from polluted area as compared with those from the control (0.0236 mg l(-1) vs. 0.014 mg l(-1); 0.0008 mg l(-1) vs. 0.0005 mg l(-1); 0.137 Um l(-1) vs. 0.055 Um l(-1), respectively). Fe level, CAT activity and TAS were lower in serum of volunteers from polluted area (0.442 g l(-1) vs. 0.476 gl(-1); 3.336 nmol min(-1)ml(-1) vs. 6.017 nmol min(-1)ml(-1); 0.731 Trolox-equivalents vs. 0.936 Trolox-equivalents, respectively), whilst differences in FRT concentration were not significant (66.109 μg l(-1) vs. 37.667 μg l(-1), p=0.3972). Positive correlations between Pb (r=0.206), Cd (r=0.602) and SOD in the inhabitants of polluted area, and between Cd and SOD in the control (r=0.639) were shown. In volunteers from both studied environments TAS-FRT (polluted: r=0.625 vs. control: r=0.837) and Fe-FRT (polluted area: r=0.831 vs. control: r=0.407) correlations, and Pb-FRT (r=0.360) and Pb-TAS (r=0.283) in the control were stated. The higher lead and cadmium concentrations in blood cause an increase of SOD activity. It suggests that this is one of the defense mechanisms of an

  9. Safety Characteristics in System Application Software for Human Rated Exploration

    NASA Technical Reports Server (NTRS)

    Mango, E. J.

    2016-01-01

    NASA and its industry and international partners are embarking on a bold and inspiring development effort to design and build an exploration class space system. The space system is made up of the Orion system, the Space Launch System (SLS) and the Ground Systems Development and Operations (GSDO) system. All are highly coupled together and dependent on each other for the combined safety of the space system. A key area of system safety focus needs to be in the ground and flight application software system (GFAS). In the development, certification and operations of GFAS, there are a series of safety characteristics that define the approach to ensure mission success. This paper will explore and examine the safety characteristics of the GFAS development.

  10. Human performance cognitive-behavioral modeling: a benefit for occupational safety

    NASA Technical Reports Server (NTRS)

    Gore, Brian F.

    2002-01-01

    Human Performance Modeling (HPM) is a computer-aided job analysis software methodology used to generate predictions of complex human-automation integration and system flow patterns with the goal of improving operator and system safety. The use of HPM tools has recently been increasing due to reductions in computational cost, augmentations in the tools' fidelity, and usefulness in the generated output. An examination of an Air Man-machine Integration Design and Analysis System (Air MIDAS) model evaluating complex human-automation integration currently underway at NASA Ames Research Center will highlight the importance to occupational safety of considering both cognitive and physical aspects of performance when researching human error.

  11. Human performance cognitive-behavioral modeling: a benefit for occupational safety.

    PubMed

    Gore, Brian F

    2002-01-01

    Human Performance Modeling (HPM) is a computer-aided job analysis software methodology used to generate predictions of complex human-automation integration and system flow patterns with the goal of improving operator and system safety. The use of HPM tools has recently been increasing due to reductions in computational cost, augmentations in the tools' fidelity, and usefulness in the generated output. An examination of an Air Man-machine Integration Design and Analysis System (Air MIDAS) model evaluating complex human-automation integration currently underway at NASA Ames Research Center will highlight the importance to occupational safety of considering both cognitive and physical aspects of performance when researching human error. PMID:12189105

  12. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations AGENCY: Centers for Disease Control and... funding available to make awards under the Centers for Disease Control and Prevention Funding...

  13. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.

    PubMed

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant.

  14. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

    PubMed Central

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant. PMID:26186596

  15. The village/commune safety policy and HIV prevention efforts among key affected populations in Cambodia: finding a balance

    PubMed Central

    2012-01-01

    The Village/Commune Safety Policy was launched by the Ministry of Interior of the Kingdom of Cambodia in 2010 and, due to a priority focus on “cleaning the streets”, has created difficulties for HIV prevention programs attempting to implement programs that work with key affected populations including female sex workers and people who inject drugs. The implementation of the policy has forced HIV program implementers, the UN and various government counterparts to explore and develop collaborative ways of delivering HIV prevention services within this difficult environment. The following case study explores some of these efforts and highlights the promising development of a Police Community Partnership Initiative that it is hoped will find a meaningful balance between the Village/Commune Safety Policy and HIV prevention efforts with key affected populations in Cambodia. PMID:22770267

  16. ANALYSIS OF DISCRIMINATING FACTORS IN HUMAN ACTIVITIES THAT AFFECT EXPOSURE

    EPA Science Inventory

    Accurately modeling exposure to particulate matter (PM) and other pollutants ultimately involves the utilization of human location-activity databases to assist in understanding the potential variability of microenvironmental exposures. This paper critically considers and stati...

  17. Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates.

    PubMed

    Feng, Ming; Li, Yan; Han, Qin; Bao, Xinjie; Yang, Ming; Zhu, Hua; Li, Qin; Wei, Junji; Ma, Wenbin; Gao, Hong; An, Yihua; Zhao, Robert Chunhua; Qin, Chuan; Wang, Renzhi

    2014-01-01

    The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.

  18. Safety.

    ERIC Educational Resources Information Center

    Education in Science, 1996

    1996-01-01

    Discusses safety issues in science, including: allergic reactions to peanuts used in experiments; explosions in lead/acid batteries; and inspection of pressure vessels, such as pressure cookers or model steam engines. (MKR)

  19. Theories of human violence: implications for health care safety.

    PubMed

    Flannery, Raymond B

    2004-01-01

    Violence is a complex, multifactorial entity with no single source of explanation. Although much research is underway into the nature and causes of violence, much of this research is done in isolation and published in highly specialized journals. Thus, there has been no journal review article for the administrator, clinician, or safety officer in health care settings who must address issues of safety on a daily basis. This paper provides that review by examining major cultural, biological, sociological, and psychological theories of violence. The review includes risk management strategies for, and the role of, health care facilities as societal institutions to curb violence. Many of the risk management strategies noted for health care settings may also be fielded in schools, courts, businesses, and other settings in which emergency services personnel are asked to respond.

  20. Aversive pavlovian responses affect human instrumental motor performance.

    PubMed

    Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

    2012-01-01

    IN NEUROSCIENCE AND PSYCHOLOGY, AN INFLUENTIAL PERSPECTIVE DISTINGUISHES BETWEEN TWO KINDS OF BEHAVIORAL CONTROL: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology.

  1. Aversive Pavlovian Responses Affect Human Instrumental Motor Performance

    PubMed Central

    Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

    2012-01-01

    In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioral control: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology. PMID:23060738

  2. Positive Affect and the Complex Dynamics of Human Flourishing

    ERIC Educational Resources Information Center

    Fredrickson, Barbara L.; Losada, Marcial F.

    2005-01-01

    Extending B. L. Fredrickson's (1998) broaden-and-build theory of positive emotions and M. Losada's (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N=188) completed an initial survey to…

  3. Hemispheric Asymmetries in Children's Perception of Nonlinguistic Human Affective Sounds

    ERIC Educational Resources Information Center

    Pollak, Seth D.; Holt, Lori L.; Fries, Alison B. Wismer

    2004-01-01

    In the present work, we developed a database of nonlinguistic sounds that mirror prosodic characteristics typical of language and thus carry affective information, but do not convey linguistic information. In a dichotic-listening task, we used these novel stimuli as a means of disambiguating the relative contributions of linguistic and affective…

  4. A robot safety experiment varying robot speed and contrast with human decision cost.

    PubMed

    Etherton, J; Sneckenberger, J E

    1990-09-01

    An industrial robot safety experiment was performed to find out how quickly subjects responded to an unexpected robot motion at different speeds of the robot arm, and how frequently they failed to detect a motion that should have been detected. Robotics technicians risk being fatally injured if a robot should trap them against a fixed object. The value of the experimentation lies in its ability to show that this risk can be reduced by a design change. If the robot is moving at a slow speed, during programming and troubleshooting tasks, then the worker has sufficient time to actuate an emergency stop device before the robot can reach the person. The dependent variable in the experiment was the overrun distance (beyond an expected stopping point) that a robot arm travelled before a person actuated a stop pushbutton. Results of this experiment demonstrated that the speed of the robot arm and the implied decision cost for hitting an emergency stop button had a significant effect on human reaction time. At a fairly high level of ambient lighting (560 lux), fixed-level changes in the luminance contrast between the robot arm and its background did not significantly affect human reaction time.

  5. Components That Affect the Personal Motivation to Implement Campus Safety Protocols

    ERIC Educational Resources Information Center

    Burt, Ernest, III

    2013-01-01

    This study examined components that have an effect on crisis response team members' personal motivation to perform campus safety protocols. The research method for this study was a quantitative design. The variables measured were compensation, experience, training, and communication. The motivation sources for this study included instrumental…

  6. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ..., better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence... clinical trials. Second, by requiring expedited reports of certain safety information that was not reported... protect human subjects enrolled in clinical trials. Under the final rule, FDA will receive...

  7. Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

    PubMed Central

    DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-01-01

    ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

  8. Polymorphic Regions Affecting Human Height Also Control Stature in Cattle

    PubMed Central

    Pryce, Jennie E.; Hayes, Ben J.; Bolormaa, Sunduimijid; Goddard, Michael E.

    2011-01-01

    Orthologous positions of 55 genes associated with height in four human populations were located on the bovine genome. Single nucleotide polymorphisms close to eight of these genes were significantly associated with stature in cattle (Bos taurus and Bos indicus). This suggests that these genes may contribute to controlling stature across mammalian species. PMID:21212230

  9. Use of animal models of human disease for nonclinical safety assessment of novel pharmaceuticals.

    PubMed

    Morgan, Sherry J; Elangbam, Chandikumar S; Berens, Shawn; Janovitz, Evan; Vitsky, Allison; Zabka, Tanja; Conour, Laura

    2013-01-01

    Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals. However, conventional (healthy) rodent and nonrodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.

  10. Neural evidence that human emotions share core affective properties.

    PubMed

    Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

    2013-06-01

    Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

  11. Testing efficacy of teaching food safety and identifying variables that affect learning in a low-literacy population.

    PubMed

    Mosby, Terezie Tolar; Romero, Angélica Lissette Hernández; Linares, Ana Lucía Molina; Challinor, Julia M; Day, Sara W; Caniza, Miguela

    2015-03-01

    Nurses at a meeting of the Asociación de Hemato Oncología Pediátrica de Centroamérica y El Caribe recognized food safety as one of the main issues affecting patient care. The objective was to increase awareness of food safety issues among caregivers for pediatric cancer patients in Guatemala and El Salvador. A low-literacy booklet about food safety, "Alimentación del niño con cáncer (Feeding the child with cancer)," was developed for caregivers. Tests were developed to assess information acquisition and retention. An educator's guide was developed for consistency of education along with a demographics questionnaire. The efficacy of the booklet was tested with 162 caregivers of patients with newly diagnosed leukemia. Information retention was tested 1 and 3 months after the initial education. The booklet was found to be efficient for food safety education. There was no significant difference between post-educational knowledge in either country at 1 month or in Guatemala at 3 months. Pre-educational knowledge was not associated with any demographic variable except for self-reported ability to read in El Salvador. There was no significant association between learning ability and demographic variables in either country. Caregivers from El Salvador had a better ability to learn than caregivers from Guatemala. Education using the booklet greatly improved food safety knowledge, which remained high 1 and 3 months later. Education with the booklet was efficacious for teaching a low-literacy population about food safety. However, it is unknown which part of the education contributed to the significant improvement in knowledge.

  12. A systematic process for assessing human spacecraft conceptual designs in terms of relative safety and operational characteristics

    NASA Astrophysics Data System (ADS)

    Higdon, Kevin Paul

    The research efforts in this dissertation are focused on reducing uncertainty in the conceptual design phase through a process of establishing a minimum functionality baseline before trading Safety and Operability in proposed spacecraft configurations. The challenge in human spacecraft development is how to combine the parts into a working design that complies with many requirements for top level mission objectives, safety, and mission success. The design methodologies presented here provides designers and decision makers with additional methods that provide an overall view of candidate design concepts. This work establishes a definition for a minimum functional design and is the first to group the fundamental mass parameters of a human spacecraft in the categories of Physics, Physiology, Safety, and Operability. The minimum functional baseline configuration described in this work is different from previous approaches because it eliminates the bias toward a minimum set of requirements. The amount of Safety in the spacecraft is the mass dedicated to safety through similar or dissimilar redundancy, safety components, margins, and dispersions. The amount of Operability in the spacecraft is the mass used to perform mission objectives and make functions easier or efficient. Because human spacecraft are highly coupled systems, the introduction of mass in one subsystem has downstream effects on other subsystems that are not easily recognized by designers and the use of rapidly reconfigurable prototypes allows designers and multidisciplinary teams to utilize Boundary Objects as a means of communication for maturing designs. The mass addition process coupled with the minimum functionality approach creates a tradespace of spacecraft configurations and provides designers with an overall view of how various levels of Safety or Operability will affect the overall spacecraft mass. The decisions made in the conceptual design phase are critical to the success of the program and

  13. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    SciTech Connect

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  14. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  15. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  16. Safe Science Facilities: Reviewing Factors that Affect Classroom Environment, Curriculum, and Safety

    ERIC Educational Resources Information Center

    Texley, Juliana

    2005-01-01

    Science teachers often have two different curricula--the ideal framework on paper and the real, day-to-day instructional program that occurs in the classroom. A number of factors can affect how much of that ideal framework is accomplished. For example, how a facility is designed and how space is used can affect student achievement, classroom…

  17. Darwinian and demographic forces affecting human protein coding genes

    PubMed Central

    Nielsen, Rasmus; Hubisz, Melissa J.; Hellmann, Ines; Torgerson, Dara; Andrés, Aida M.; Albrechtsen, Anders; Gutenkunst, Ryan; Adams, Mark D.; Cargill, Michele; Boyko, Adam; Indap, Amit; Bustamante, Carlos D.; Clark, Andrew G.

    2009-01-01

    Past demographic changes can produce distortions in patterns of genetic variation that can mimic the appearance of natural selection unless the demographic effects are explicitly removed. Here we fit a detailed model of human demography that incorporates divergence, migration, admixture, and changes in population size to directly sequenced data from 13,400 protein coding genes from 20 European-American and 19 African-American individuals. Based on this demographic model, we use several new and established statistical methods for identifying genes with extreme patterns of polymorphism likely to be caused by Darwinian selection, providing the first genome-wide analysis of allele frequency distributions in humans based on directly sequenced data. The tests are based on observations of excesses of high frequency–derived alleles, excesses of low frequency–derived alleles, and excesses of differences in allele frequencies between populations. We detect numerous new genes with strong evidence of selection, including a number of genes related to psychiatric and other diseases. We also show that microRNA controlled genes evolve under extremely high constraints and are more likely to undergo negative selection than other genes. Furthermore, we show that genes involved in muscle development have been subject to positive selection during recent human history. In accordance with previous studies, we find evidence for negative selection against mutations in genes associated with Mendelian disease and positive selection acting on genes associated with several complex diseases. PMID:19279335

  18. Human Sensing Fusion Project for Safety and Health Society

    NASA Astrophysics Data System (ADS)

    Maenaka, Kazusuke

    This paper introduces objectives and status of “Human sensing fusion project” in the Exploratory Research for Advanced Technology (ERATO) scheme produced by Japan Science and Technology Agency (JST). This project was started in December 2007 and the laboratory with 11 members opened on April 2008. The aim of this project is to realize a human activity-monitoring device with many kinds of sensors in ultimate small size so that the device can be pasted or patched to the human body, and to establish the algorism for understanding human condition including both physical and mental conditions from obtained data. This system can be used towards the prevention of the danger of accidents and the maintenance of health. The actual research has just begun and preparations for project are well under way.

  19. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    PubMed

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  20. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape

    PubMed Central

    Moreira-Arce, Dario; Vergara, Pablo M.; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants and

  1. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    PubMed

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  2. How the choice of safety performance function affects the identification of important crash prediction variables.

    PubMed

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects.

  3. Occupational health and safety issues affecting young workers: a literature review.

    PubMed

    Laberge, Marie; Ledoux, Elise

    2011-01-01

    Many overview articles, reports, book chapters and literature reviews have examined the health and safety of young workers. These sources discuss the relationships between the work conditions of young workers and the various indicators of accidents and occupational diseases. Breslin et al. [12,13] conducted two literature reviews of quantitative studies to determine which factors best predicted work accidents and occupational disorders in young people. The present article proposes a review of young people's occupational health and safety (OHS) factors (e.g., demographic, individual, professional, organizational, temporal and operational factors) in both qualitative and quantitative studies. Five types of problems were analyzed in greater depth, namely MSD symptoms, respiratory, allergy and toxicological problems, mental health and well-being, alcohol and drug consumption, and fatigue. This review likewise examines related dimensions that allow us to adopt a more global perspective on this subject by considering such elements as young people's values, their knowledge and attitudes, safety practices in companies, the safe integration of young people, and rehabilitation. A total of 189 scientific articles were selected on the basis of certain criteria. These articles came from refereed OHS journals published between 1994 and 2005.

  4. How the choice of safety performance function affects the identification of important crash prediction variables.

    PubMed

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects. PMID:26710265

  5. Numerical human models for accident research and safety - potentials and limitations.

    PubMed

    Praxl, Norbert; Adamec, Jiri; Muggenthaler, Holger; von Merten, Katja

    2008-01-01

    The method of numerical simulation is frequently used in the area of automotive safety. Recently, numerical models of the human body have been developed for the numerical simulation of occupants. Different approaches in modelling the human body have been used: the finite-element and the multibody technique. Numerical human models representing the two modelling approaches are introduced and the potentials and limitations of these models are discussed.

  6. How sensory properties of foods affect human feeding behavior.

    PubMed

    Rolls, B J; Rowe, E A; Rolls, E T

    1982-09-01

    The sensory properties of food which can lead to a decrease in the pleasantness of that food after it is eaten, and to enhanced food intake if that property of the food is changed by successive presentation of different foods, were investigated. After eating chocolates of one color the pleasantness of the taste of the eaten color declined more than of the non-eaten colors, although these chocolates differed only in appearance. The presentation of a variety of colors of chocolates, either simultaneously or successively, did not affect food intake compared with consumption of the subject's favorite color. Changes in the shape of food (which affects both appearance and mouth feel) were introduced by offering subjects three successive courses consisting of different shapes of pasta. Changes in shape led to a specific decrease in the pleasantness of the shape eaten and to a significant enhancement (14%) of food intake when three shapes were offered compared with intake of the subject's favorite shape. Changes in just the flavor of food (i.e., cream cheese sandwiches flavored with salt, or with the non-nutritive flavoring agents lemon and saccharin, or curry) led to a significant enhancement (15%) of food intake when all three flavors were presented successively compared with intake of the favorite. The experiments elucidate some of the properties of food which are involved in sensory specific satiety, and which determine the amount of food eaten. PMID:7178247

  7. Human erythrocytes are affected by the organochloride insecticide chlordane.

    PubMed

    Suwalsky, M; Rodríguez, C; Villena, F; Sotomayor, C P

    2005-05-01

    Chlordane is a widely used organochlorine insecticide. In order to evaluate its perturbing effect upon the morphology of human erythrocytes it was caused to interact with human red cells and molecular models of cell membranes. These consisted in bilayers of dimyristoylphosphatidylethanolamine (DMPE) and of dimyristoylphosphatidylcholine (DMPC), representative of phospholipid classes located in the inner and outer monolayers of the erythrocyte membrane, respectively. Scanning electron microscopy (SEM) observations indicated that this pesticide induced a significant alteration in the shape of the erythrocytes as they changed their discoid shape to spherocytes. According to the bilayer couple hypothesis, the shape changes induced in erythrocytes by foreign molecules are due to differential expansion of their two monolayers. The fact that chlordane produced spherocytes would indicate that the pesticide was equally located in the outer and the inner moieties of the red cell membrane. This conclusion was supported by the results obtained from X-ray diffraction studies. These showed that the hydrophobic and polar head regions of DMPC bilayers were perturbed when the insecticide was in a 1:10 molar ratio with respect to the lipid. These results were confirmed by the fluorescence experiments performed in DMPC large unilamellar vesicles (LUV). Chlordane produced a sharp decrease in the anisotropy and general polarization parameters in the 0-0.1 mM range, implying an increase in the fluidity at the acyl chain and polar region of DMPC. On the other hand, the bilayer structure of DMPE was perturbed in a fashion similar to that observed by X-ray diffraction in DMPC, a fact that explains the morphological change induced by chlordane to the human erythrocytes. PMID:15778003

  8. Factors affecting speed in human-powered vehicles.

    PubMed

    White, A P

    1994-10-01

    It is shown how to derive the appropriate cubic equation relating power and the effects of friction, gradient and wind resistance on the speed of a human-powered vehicle (HPV). The effects of gradient and wind resistance are explored for parameters representing a typical racing cyclist. The principal conclusion may be summarized as follows: for optimum performance in a time trial, there should be no wind and the course should be level. Any deviation from these conditions will produce a decrement in performance.

  9. Disturbances of electrodynamic activity affect abortion in human

    NASA Astrophysics Data System (ADS)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  10. Capturing Safety Requirements to Enable Effective Task Allocation Between Humans and Automaton in Increasingly Autonomous Systems

    NASA Technical Reports Server (NTRS)

    Neogi, Natasha A.

    2016-01-01

    There is a current drive towards enabling the deployment of increasingly autonomous systems in the National Airspace System (NAS). However, shifting the traditional roles and responsibilities between humans and automation for safety critical tasks must be managed carefully, otherwise the current emergent safety properties of the NAS may be disrupted. In this paper, a verification activity to assess the emergent safety properties of a clearly defined, safety critical, operational scenario that possesses tasks that can be fluidly allocated between human and automated agents is conducted. Task allocation role sets were proposed for a human-automation team performing a contingency maneuver in a reduced crew context. A safety critical contingency procedure (engine out on takeoff) was modeled in the Soar cognitive architecture, then translated into the Hybrid Input Output formalism. Verification activities were then performed to determine whether or not the safety properties held over the increasingly autonomous system. The verification activities lead to the development of several key insights regarding the implicit assumptions on agent capability. It subsequently illustrated the usefulness of task annotations associated with specialized requirements (e.g., communication, timing etc.), and demonstrated the feasibility of this approach.

  11. Human monocyte differentiation stage affects response to arachidonic acid.

    PubMed

    Escobar-Alvarez, Elizabeth; Pelaez, Carlos A; García, Luis F; Rojas, Mauricio

    2010-01-01

    AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.

  12. International study of factors affecting human chromosome translocations

    PubMed Central

    Sigurdson, Alice J.; Ha, Mina; Hauptmann, Michael; Bhatti, Parveen; Sram, Radim J.; Beskid, Olena; Tawn, E. Janet; Whitehouse, Caroline A.; Lindholm, Carita; Nakano, Mimako; Kodama, Yoshiaki; Nakamura, Nori; Vorobtsova, Irena; Oestreicher, Ursula; Stephan, Günther; Yong, Lee C.; Bauchinger, Manfred; Schmid, Ernst; Chung, Hai Won; Darroudi, Firouz; Roy, Laurence; Voisin, Phillipe; Barquinero, Joan F.; Livingston, Gordon; Blakey, David; Hayata, Isamu; Zhang, Wei; Wang, Chunyan; Bennett, L. Michelle; Littlefield, L. Gayle; Edwards, Alan A.; Kleinerman, Ruth A.; Tucker, James D.

    2009-01-01

    Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from sixteen laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages vs. a linear relationship (p <0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09–1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. PMID:18337160

  13. Conjugated linoleic acid supplementation for 8 weeks does not affect body composition, lipid profile, or safety biomarkers in overweight, hyperlipidemic men.

    PubMed

    Joseph, Shama V; Jacques, Hélène; Plourde, Mélanie; Mitchell, Patricia L; McLeod, Roger S; Jones, Peter J H

    2011-07-01

    The usefulness of conjugated linoleic acid (CLA) as a nutraceutical remains ambiguous. Our objective was, therefore, to investigate the effect of CLA on body composition, blood lipids, and safety biomarkers in overweight, hyperlipidemic men. A double-blinded, 3-phase crossover trial was conducted in overweight (BMI ≥ 25 kg/m(2)), borderline hypercholesterolemic [LDL-cholesterol (C) ≥ 2.5 mmol/L] men aged 18-60 y. During three 8-wk phases, each separated by a 4-wk washout period, 27 participants consumed under supervision in random order 3.5 g/d of safflower oil (control), a 50:50 mixture of trans 10, cis 12 and cis 9, trans 11 (c9, t11) CLA:Clarinol G-80, and c9, t11 isomer:c9, t11 CLA. At baseline and endpoint of each phase, body weight, body fat mass, and lean body mass were measured by DXA. Blood lipid profiles and safety biomarkers, including insulin sensitivity, blood concentrations of adiponectin, and inflammatory (high sensitive-C-reactive protein, TNFα, and IL-6) and oxidative (oxidized-LDL) molecules, were measured. The effect of CLA consumption on fatty acid oxidation was also assessed. Compared with the control treatment, the CLA treatments did not affect changes in body weight, body composition, or blood lipids. In addition, CLA did not affect the β-oxidation rate of fatty acids or induce significant alterations in the safety markers tested. In conclusion, although no detrimental effects were caused by supplementation, these results do not confirm a role for CLA in either body weight or blood lipid regulation in humans.

  14. Environmental and human safety of major surfactants. Volume 1. Anionic surfactants. Part 1. Linear alkylbenzene sulfonates. Final report

    SciTech Connect

    Not Available

    1991-02-01

    The report discusses critical reviews of published literature and unpublished company data on major surfactants. Part 1 of Vol. 1 discusses the chemistry, biodegradation, environmental effects and safety and human safety of linear alkylbenzene sulfonates. The information presented updates and supplements similar data included in two predecessor studies, Human Safety and Environmental Aspects of Major Surfactants (1977) NTIS Accession Number PB-301193 and Human and Environmental Aspects of Major Surfactants (Supplement) (1981) NTIS Accession Number PB-81-182453.

  15. Environmental and human safety of major surfactants. Volume 1. Anionic surfactants. Part 3. Alkyl sulfates. Final report

    SciTech Connect

    Not Available

    1991-02-01

    The report discusses critical reviews of published literature and unpublished company data on major surfactants. Part 3 of Vol. 1 discusses the chemistry, biodegradation, environmental effects and safety and human safety of alkyl sulfates. The information presented updates and supplements similar data included in two predecessor studies, Human Safety and Environmental Aspects of Major Surfactants (1977) NTIS Accession Number PB301193 and Human and Environmental Aspects of Major Surfactants (Supplement) (1981) NTIS Accession Number PB81-182453.

  16. Environmental and human safety of major surfactants. Volume 1. Anionic surfactants. Part 2. Alcohol ethoxy sulfates. Final report

    SciTech Connect

    Not Available

    1991-02-01

    The report discusses critical reviews of published literature and unpublished company data on major surfactants. Part 2 of Vol. 1 discusses the chemistry, biodegradation, environmental effects and safety and human safety of alcohol ethoxy sulfates. The information presented updates and supplements similar data included in two predecessor studies, Human Safety and Environmental Aspects of Major Surfactants (1977) NTIS Accession Number PB301193 and Human and Environmental Aspects of Major Surfactants (Supplement) (1981) NTIS Accessiion Number PB81-182453.

  17. Pregnancy does not affect human olfactory detection thresholds.

    PubMed

    Cameron, E Leslie

    2014-02-01

    Hyperosmia is suspected in pregnancy; however, no empirical study using validated measures of olfactory function has clearly confirmed the anecdotal reports of this phenomenon. The goal of the current study is to compare the olfactory sensitivity of pregnant women to that of nonpregnant women and men. All participants rated their sense of smell and pregnant women listed the odors to which they were most sensitive. Detection thresholds were measured using a well-validated protocol. A group of pregnant and nonpregnant women was studied longitudinally using a signal detection procedure designed to detect small differences in sensitivity. Pregnant women, particularly in the 1st trimester, rated their sense of smell to be higher than nonpregnant women and men and indicated many (primarily unpleasant) odors to which they were more sensitive. Women rated their sense of smell higher than men. However, there was no sex difference in thresholds and neither thresholds nor signal detection measures of sensitivity were significantly affected by either sex or pregnancy status. The implications of the lack of relationship between self-report and measures of olfactory sensitivity, particularly in pregnancy, are discussed.

  18. MISR Satellite Observations of Aerosol Types Affecting Human Health

    NASA Astrophysics Data System (ADS)

    Kalashnikova, O. V.; Franklin, M.; Garay, M. J.; Diner, D. J.

    2015-12-01

    Ground-based observations of pollutants and concentrations of particulate matter (PM), that includes small particles designated PM2.5 and dust-dominated PM10, are the gold standard in studies of environmental impacts on human health. However, because monitoring stations are costly, they typically provide only limited spatial coverage, especially in rural and remote areas. We will demonstrate how data from the Multi-angle Imaging SpectroRadiometer (MISR) instrument that has been flying on NASA's Terra Earth Observing System satellite since early 2000 can be used to provide estimates of surface PM types. The current MISR operational aerosol retrieval uses a combination of multi-spectral and multi-angle data to retrieve aerosol optical depth (AOD) and particle property information (including dust AOD) globally at 17.6 km spatial resolution. Using the same algorithm with data collected in all 36-channels at 275 m resolution (Local Mode), which is available over greater Los Angeles area, and also was activated during 2013 DISCOVER-AQ California field campaign, high-resolution 4.4 km aerosol retrievals were performed in addition to the standard 17.6 km retrievals. The 4.4 km spatial resolution of the PM information data is fine enough to be able to resolve local differences in PM loading that may be important for understanding regional health effects of pollution in the region. In particular, we demonstrate that MISR high-resolution AOD retrievals are in better agreement with ground-based aerosol observations and reveal more details about the aerosol spatial variability compared to the MISR standard 17.6 km product. Then we will discuss techniques and show examples of the application of high-resolution MISR data to provide estimates of surface PM for the greater Los Angeles area in 2008 and for California San Joaquin Valley during the 2013 DISCOVER-AQ field campaign. Finally, we will discuss future NASA instruments that will provide new information allowing for better

  19. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    SciTech Connect

    Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

    2014-09-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  20. Mimicry profiles are affected by human-induced habitat changes.

    PubMed Central

    Azmeh, S; Owen, J; Sørensen, K; Grewcock, D; Gilbert, F

    1998-01-01

    Mimicry theory predicts that mimics in a Batesian mimicry complex evolve to resemble models closely, and that there is a limit on the numbers of mimics relative to models. For hoverflies (Diptera: Syrphidae), supposed mimics of social wasps (Hymenoptera: Vespidae, neither of these is true; many mimics are imperfect and in the UK and Europe they outnumber their models manifold. We hypothesized that the high abundance of mimics relative to models in the UK may be the result not just of mimic model dynamics, but of habitat changes caused by humans. Most of the larvae of poor mimics are aphidophagous, and changes from ancient forest to agricultural and/or urban habitats may have vastly augmented aphid numbers. Using new and literature data, we compared mimicry profiles of habitats differing in their degree of habitat disturbance. In both cases more highly disturbed habitats had proportionally more poor mimics and fewer high-fidelity mimics than less disturbed habitats. This supports the hypothesis that habitat change has an effect on model to mimic ratios. PMID:9881474

  1. Mimicry profiles are affected by human-induced habitat changes.

    PubMed

    Azmeh, S; Owen, J; Sørensen, K; Grewcock, D; Gilbert, F

    1998-12-01

    Mimicry theory predicts that mimics in a Batesian mimicry complex evolve to resemble models closely, and that there is a limit on the numbers of mimics relative to models. For hoverflies (Diptera: Syrphidae), supposed mimics of social wasps (Hymenoptera: Vespidae, neither of these is true; many mimics are imperfect and in the UK and Europe they outnumber their models manifold. We hypothesized that the high abundance of mimics relative to models in the UK may be the result not just of mimic model dynamics, but of habitat changes caused by humans. Most of the larvae of poor mimics are aphidophagous, and changes from ancient forest to agricultural and/or urban habitats may have vastly augmented aphid numbers. Using new and literature data, we compared mimicry profiles of habitats differing in their degree of habitat disturbance. In both cases more highly disturbed habitats had proportionally more poor mimics and fewer high-fidelity mimics than less disturbed habitats. This supports the hypothesis that habitat change has an effect on model to mimic ratios.

  2. The efficacy and safety of human oocyte vitrification.

    PubMed

    Nagy, Zsolt Peter; Chang, Ching-Chien; Shapiro, Daniel B; Bernal, Diana Patricia; Kort, Hilton I; Vajta, Gábor

    2009-11-01

    Vitrification is now a widely applied and highly successful approach for cryopreservation in reproductive biology. Rapidly increasing data prove that it is also a highly efficient technique for low-temperature storage of human oocytes. The latest approaches with appropriately selected cryoprotectants, tools and techniques, and properly adjusted parameters allow close to 100% morphological survival rates, and in vitro embryo development, as well pregnancy and implantation rates, comparable with those achieved with fresh oocytes. With standardization of the technique and elimination of biosafety problems by preserving all the positive features, vitrification may become a common part of the everyday routine in a human embryo laboratory, and it may offer a solution for various medical and social situations as well as for simple logistic problems commonly occurring in assisted reproduction. PMID:19806513

  3. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  4. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

  5. Human safety study of body lotion containing Kathon CG.

    PubMed

    Schwartz, S R; Weiss, S; Stern, E; Morici, I J; Moss, J N; Goodman, J J; Scarborough, N L

    1987-04-01

    The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

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

    PubMed

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

    2011-01-01

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

  7. Sociopsychological factors affecting the human response to noise exposure.

    PubMed

    Borsky, P N

    1979-08-01

    Community noise is reported to be the most often mentioned undesirable neighborhood condition in a recent U.S. Census survey. Understanding community response to noise involves the measurement of a number of complex acoustic and nonacoustic variables and establishing the chain of relationships between physical exposure, perception, annoyance, and acceptability responses and finally complaint behavior. The perceived loudness of a noise is the most important acoustic parameter influencing annoyance and complaints, and the simple dBA unit can be used to integrate spectral characteristics of complex sounds in community studies. Although energy averaging such as Leq or Ldn can be used to describe multiple noise exposures over time, the variable trade-off relationships between number and level of exposures are somewhat obscured by such summary measures. However, they are still the best available descriptors and, until more accurate ones are developed, can be used to measure community noise environments. Perception of an identical noise exposure can vary according to the physiological noise sensitivity of a person and the activity context in which the noise is heard. Although the acoustic quality of the noise itself usually explains about 10 to 25 per cent of the variability in annoyance responses, sociopsychological variables measured in field studies account for 35 to 50 per cent of the variations in human annoyance responses. Three of the most important nonacoustic factors are the connotative fear effects of the noise signal, the feeling that those responsible for the noise are misfeasant in not reducing the noise, and the feeling that harmful health effects are produced by the noise. When residents report great fear, a high misfeasance, and marked health effects, about 90 per cent report a high annoyance level whether their noise exposure level is above 90 Ldn or 65 to 70 Ldn. In contrast, if the feelings are a low fear level, a low degree of misfeasance, and minimal

  8. Pregnancy and Preeclampsia Affect Monocyte Subsets in Humans and Rats

    PubMed Central

    Borghuis, Theo; Klok, Pieter A.; Groen, Bart; Bolt, Annemarie; de Vos, Paul; van Pampus, Maria G.; Wong, Tsz Y.; van Goor, Harry; Bakker, Winston W.; Faas, Marijke M.

    2012-01-01

    Introduction Both nonclassical and intermediate monocytes have been implicated in different inflammatory conditions. We hypothesized that these monocytes would increase during pregnancy, a condition associated with generalized activation of inflammatory responses and that they would increase even more during preeclampsia, in which inflammatory responses are further stimulated. In the present study we investigated changes in monocyte subsets during healthy pregnancy and preeclampsia in humans and rats. Methods Blood monocyte subsets of nonpregnant, preeclamptic and healthy pregnant women were identified with CD14 and CD16. In nonpregnant and pregnant rats, blood monocytes were identified with CD172a and CD43, as well as in rats infused with adenosine triphosphate (ATP), a pro-inflammatory stimulus known to induce preeclampsia-like symptoms. Total and CD206-positive macrophages were quantified in placentas of these animals. Results Lower percentages of classical monocytes were found in pregnant women (91%–[83–98%]) compared to nonpregnant women (94%–[90–98%]) and even less in preeclamptic patients (90%–[61–92%]). In contrast, the percentage of combined nonclassical/intermediate monocytes was higher in pregnant women (8.5%–[2.3–16.6%] vs. 5.6%–[1.9–9.5%]) and even higher in preeclamptic patients (9.9%–[7.8–38.7%]), which was caused by a selective increase of intermediate monocytes. In rats, we also found lower percentages of classical monocytes and higher percentages of nonclassical monocytes in pregnant versus nonpregnant rats. ATP infusion increased the percentage of nonclassical monocytes in pregnant rats even further but not in nonpregnant rats. These nonclassical monocytes showed a more activated phenotype in pregnant ATP-infused rats only. Mesometrial triangles of ATP-infused rats had less CD206-positive macrophages as compared to those of saline-infused rats. Conclusion The higher percentage of nonclassical/intermediate monocytes found

  9. Forced expression of chimeric human fibroblast tropomyosin mutants affects cytokinesis

    PubMed Central

    1995-01-01

    Human fibroblasts generate at least eight tropomyosin (TM) isoforms (hTM1, hTM2, hTM3, hTM4, hTM5, hTM5a, hTM5b, and hTMsm alpha) from four distinct genes, and we have previously demonstrated that bacterially produced chimera hTM5/3 exhibits an unusually high affinity for actin filaments and a loss of the salt dependence typical for TM-actin binding (Novy, R.E., J. R. Sellers, L.-F. Liu, and J.J.-C. Lin, 1993. Cell Motil. & Cytoskeleton. 26: 248-261). To examine the functional consequences of expressing this mutant TM isoform in vivo, we have transfected CHO cells with the full-length cDNA for hTM5/3 and compared them to cells transfected with hTM3 and hTM5. Immunofluorescence microscopy reveals that stably transfected CHO cells incorporate force- expressed hTM3 and hTM5 into stress fibers with no significant effect on general cell morphology, microfilament organization or cytokinesis. In stable lines expressing hTM5/3, however, cell division is slow and sometimes incomplete. The doubling time and the incidence of multinucleate cells in the stable hTM5/3 lines roughly parallel expression levels. A closely related chimeric isoform hTM5/2, which differs only in the internal, alternatively spliced exon also produces defects in cytokinesis, suggesting that normal TM function may involve coordination between the amino and carboxy terminal regions. This coordination may be prevented in the chimeric mutants. As bacterially produced hTM5/3 and hTM5/2 can displace hTM3 and hTM5 from actin filaments in vitro, it is likely that CHO-expressed hTM5/3 and hTM5/2 can displace endogenous TMs to act dominantly in vivo. These results support a role for nonmuscle TM isoforms in the fine tuning of microfilament organization during cytokinesis. Additionally, we find that overexpression of TM does not stabilize endogenous microfilaments, rather, the hTM-expressing cells are actually more sensitive to cytochalasin B. This suggests that regulation of microfilament integrity in vivo

  10. Determining the safety of microbial cultures for consumption by humans and animals.

    PubMed

    Pariza, Michael W; Gillies, Kevin O; Kraak-Ripple, Sarah F; Leyer, Gregory; Smith, Amy B

    2015-10-01

    Fermented foods and feeds have been consumed for millennia, and microorganisms isolated from traditional fermentations have been used as probiotics. There is interest in developing new microbial cultures for these uses, but to date safety evaluation procedures have only been discussed in general terms. We propose a comprehensive approach for determining the safety of microbial cultures that lack an established history of safe use for their intended new applications. Three scenarios are considered: (1) substantially increased exposure to a culture that has an established record of safety in a more limited application; (2) a new strain without a history of safe use that was isolated from a food or feed that has a history of safe use; and (3) a new strain isolated from a non-food or non-feed source. Our safety evaluation process is based on scientific procedures and is in the form of a decision tree composed of 13 questions. Our decision tree for determining the safety of microbial cultures for consumption by humans or animals is modeled on previous decision trees that are used worldwide to evaluate the safety of microbial enzymes for use in human food or animal feed.

  11. Self-portrayal concerns and their relation to safety behaviors and negative affect in social anxiety disorder.

    PubMed

    Moscovitch, David A; Rowa, Karen; Paulitzki, Jeffrey R; Ierullo, Maria D; Chiang, Brenda; Antony, Martin M; McCabe, Randi E

    2013-08-01

    It has been proposed that self-portrayal concerns - fundamental worries that particular negative self-attributes will become exposed during social encounters and criticized by others - underlie the experience of social anxiety (SA) and drive associated avoidance and safety behaviors (Moscovitch, 2009). The development of the Negative Self Portrayal Scale (NSPS) to assess such concerns across the dimensions of social competence, signs of anxiety, and physical appearance has helped yield promising initial findings that support the basic tenets of Moscovitch's (2009) theoretical model in samples of undergraduate students (Moscovitch & Huyder, 2011). The present study investigated the nature of self-portrayal concerns and their relation to affect and behavior in a sample of 194 community-based participants consisting of (a) 62 individuals with a principal diagnosis of generalized SAD, either with (n = 35) or without (n = 27) an additional depressive disorder diagnosis, (b) 51 individuals with another principal anxiety disorder diagnosis, either with (n = 22) or without (n = 29) an additional diagnosis of SAD, and (c) 81 healthy controls. Participants completed trait questionnaires, daily diaries of naturalistic social encounters, and a laboratory-based speech task. Results demonstrated (a) that a diagnosis of SAD confers unique risk for elevated self-portrayal concerns, (b) that such concerns predict significant variance in safety behavior use across diverse contexts, and (c) that the use of safety behaviors mediates the relation between such concerns and the experience of heightened negative affect. Implications for case conceptualization and treatment of SAD are discussed.

  12. Self-portrayal concerns and their relation to safety behaviors and negative affect in social anxiety disorder.

    PubMed

    Moscovitch, David A; Rowa, Karen; Paulitzki, Jeffrey R; Ierullo, Maria D; Chiang, Brenda; Antony, Martin M; McCabe, Randi E

    2013-08-01

    It has been proposed that self-portrayal concerns - fundamental worries that particular negative self-attributes will become exposed during social encounters and criticized by others - underlie the experience of social anxiety (SA) and drive associated avoidance and safety behaviors (Moscovitch, 2009). The development of the Negative Self Portrayal Scale (NSPS) to assess such concerns across the dimensions of social competence, signs of anxiety, and physical appearance has helped yield promising initial findings that support the basic tenets of Moscovitch's (2009) theoretical model in samples of undergraduate students (Moscovitch & Huyder, 2011). The present study investigated the nature of self-portrayal concerns and their relation to affect and behavior in a sample of 194 community-based participants consisting of (a) 62 individuals with a principal diagnosis of generalized SAD, either with (n = 35) or without (n = 27) an additional depressive disorder diagnosis, (b) 51 individuals with another principal anxiety disorder diagnosis, either with (n = 22) or without (n = 29) an additional diagnosis of SAD, and (c) 81 healthy controls. Participants completed trait questionnaires, daily diaries of naturalistic social encounters, and a laboratory-based speech task. Results demonstrated (a) that a diagnosis of SAD confers unique risk for elevated self-portrayal concerns, (b) that such concerns predict significant variance in safety behavior use across diverse contexts, and (c) that the use of safety behaviors mediates the relation between such concerns and the experience of heightened negative affect. Implications for case conceptualization and treatment of SAD are discussed. PMID:23778055

  13. How does enhancing cognition affect human values? How does this translate into social responsibility?

    PubMed

    Cabrera, Laura Y

    2015-01-01

    The past decade has seen a rise in the use of different technologies aimed at enhancing cognition of normal healthy individuals. While values have been acknowledged to be an important aspect of cognitive enhancement practices, the discussion has predominantly focused on just a few values, such as safety, peer pressure, and authenticity. How are values, in a broader sense, affected by enhancing cognitive abilities? Is this dependent on the type of technology or intervention used to attain the enhancement, or does the cognitive domain targeted play a bigger role in how values are affected? Values are not only likely to be affected by cognitive enhancement practices; they also play a crucial role in defining the type of interventions that are likely to be undertaken. This paper explores the way values affect and are affected by enhancing cognitive abilities. Furthermore, it argues that knowledge of the interplay between values and cognitive enhancement makes a strong case for social responsibility around cognitive enhancement practices.

  14. Food safety: are human activities really worse than nature's?

    PubMed

    Clayson, D B

    1993-04-01

    Those chemicals that are added to food during modern processing are most stringently examined for toxic effects and, if they demonstrate toxicity, are strictly controlled. Despite this, a considerable proportion of the North American human cancer burden has been associated with diet and nutrition. The possible contributions of excess calories, excess and wrongly balanced fats, natural contaminants, and naturally occurring carcinogens within the food supply to this horrendous burden of cancer is considered. The theoretically possible use of bioengineering techniques to modify the composition of food crops and thus to minimize the levels of carcinogens in the food supply is discussed. This is considered important since failure to monitor the effect of bioengineering may lead to an increase in the level of such noxious agents, especially if the goal of such bioengineering is to develop food crops with increased intrinsic resistance to pests and other spoilage organisms.

  15. Preclinical Studies on the Pharmacokinetics, Safety and Toxicology of Oxfendazole: Toward First in Human Studies

    PubMed Central

    Codd, Ellen E.; Ng, Hanna H.; McFarlane, Claire; Riccio, Edward S.; Doppalapudi, Rupa; Mirsalis, Jon C.; Horton, R. John; Gonzalez, Armando E.; Garcia, H. Hugo; Gilman, Robert H.

    2015-01-01

    A two-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased WBC levels, a class effect of benzimidazole anthelminthics, returned to normal during the recovery period. The NOAEL was determined to be >5 but < 25 mg/kg/d and the MTD 100 mg/kg/d. The highest dose, 200 mg/kg/d resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after seven days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma or rat micronucleus assays, nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases. PMID:25701764

  16. Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

    PubMed

    Zeng, Wei; Zhang, Shuying; Liu, Dai; Chai, Mi; Wang, Jiaqi; Zhao, Yuming

    2014-01-01

    Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.

  17. A severe human ESD (electrostatic discharge) model for safety and high reliability system qualification testing

    SciTech Connect

    Fisher, R J

    1989-01-01

    A severe human electrostatic discharge (ESD) equivalent source model has been developed for use in qualification testing of systems that have stringent safety or very high reliability requirements. The model produces the now-acknowledged worst-case waveform, and the values of the constituent components have been selected from measured human body electrical parameters to maximize the peak amplitude and rate of rise of the short-circuit discharge current and energy transfer to the victim system. 18 refs., 5 figs.

  18. To illuminate or not to illuminate: roadway lighting as it affects traffic safety at intersections.

    PubMed

    Bullough, John D; Donnell, Eric T; Rea, Mark S

    2013-04-01

    A two-pronged effort to quantify the impact of lighting on traffic safety is presented. In the statistical approach, the effects of lighting on crash frequency for different intersection types in Minnesota were assessed using count regression models. The models included many geometric and traffic control variables to estimate the association between lighting and nighttime and daytime crashes and the resulting night-to-day crash ratios. Overall, the presence of roadway intersection lighting was found to be associated with an approximately 12% lower night-to-day crash ratio than unlighted intersections. In the parallel analytical approach, visual performance analyses based on roadway intersection lighting practices in Minnesota were made for the same intersection types investigated in the statistical approach. The results of both approaches were convergent, suggesting that visual performance improvements from roadway lighting could serve as input for predicting improvements in crash frequency. A provisional transfer function allows transportation engineers to evaluate alternative lighting systems in the design phase so selections based on expected benefits and costs can be made.

  19. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals.

    PubMed

    Beyerle, Andrea; Nolte, Marc W; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5-2.0g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent.

  20. Practical Applications of Cosmic Ray Science: Spacecraft, Aircraft, Ground Based Computation and Control Systems and Human Health and Safety

    NASA Technical Reports Server (NTRS)

    Atwell, William; Koontz, Steve; Normand, Eugene

    2012-01-01

    In this paper we review the discovery of cosmic ray effects on the performance and reliability of microelectronic systems as well as on human health and safety, as well as the development of the engineering and health science tools used to evaluate and mitigate cosmic ray effects in earth surface, atmospheric flight, and space flight environments. Three twentieth century technological developments, 1) high altitude commercial and military aircraft; 2) manned and unmanned spacecraft; and 3) increasingly complex and sensitive solid state micro-electronics systems, have driven an ongoing evolution of basic cosmic ray science into a set of practical engineering tools (e.g. ground based test methods as well as high energy particle transport and reaction codes) needed to design, test, and verify the safety and reliability of modern complex electronic systems as well as effects on human health and safety. The effects of primary cosmic ray particles, and secondary particle showers produced by nuclear reactions with spacecraft materials, can determine the design and verification processes (as well as the total dollar cost) for manned and unmanned spacecraft avionics systems. Similar considerations apply to commercial and military aircraft operating at high latitudes and altitudes near the atmospheric Pfotzer maximum. Even ground based computational and controls systems can be negatively affected by secondary particle showers at the Earth's surface, especially if the net target area of the sensitive electronic system components is large. Accumulation of both primary cosmic ray and secondary cosmic ray induced particle shower radiation dose is an important health and safety consideration for commercial or military air crews operating at high altitude/latitude and is also one of the most important factors presently limiting manned space flight operations beyond low-Earth orbit (LEO).

  1. A Customized Vision System for Tracking Humans Wearing Reflective Safety Clothing from Industrial Vehicles and Machinery

    PubMed Central

    Mosberger, Rafael; Andreasson, Henrik; Lilienthal, Achim J.

    2014-01-01

    This article presents a novel approach for vision-based detection and tracking of humans wearing high-visibility clothing with retro-reflective markers. Addressing industrial applications where heavy vehicles operate in the vicinity of humans, we deploy a customized stereo camera setup with active illumination that allows for efficient detection of the reflective patterns created by the worker's safety garments. After segmenting reflective objects from the image background, the interest regions are described with local image feature descriptors and classified in order to discriminate safety garments from other reflective objects in the scene. In a final step, the trajectories of the detected humans are estimated in 3D space relative to the camera. We evaluate our tracking system in two industrial real-world work environments on several challenging video sequences. The experimental results indicate accurate tracking performance and good robustness towards partial occlusions, body pose variation, and a wide range of different illumination conditions. PMID:25264956

  2. An Evaluation of the Effects of Human Factors and Ergonomics on Health Care and Patient Safety Practices: A Systematic Review

    PubMed Central

    Zhang, Longhao; Zhao, Pujing; Chen, Ying; Zhang, Mingming

    2015-01-01

    Background From the viewpoint of human factors and ergonomics (HFE), errors often occur because of the mismatch between the system, technique and characteristics of the human body. HFE is a scientific discipline concerned with understanding interactions between human behavior, system design and safety. Objective To evaluate the effectiveness of HFE interventions in improving health care workers’ outcomes and patient safety and to assess the quality of the available evidence. Methods We searched databases, including MEDLINE, EMBASE, BIOSIS Previews and the CBM (Chinese BioMedical Literature Database), for articles published from 1996 to Mar.2015. The quality assessment tool was based on the risk of bias criteria developed by the Cochrane Effective Practice and Organization of Care (EPOC) Group. The interventions of the included studies were categorized into four relevant domains, as defined by the International Ergonomics Association. Results For this descriptive study, we identified 8, 949 studies based on our initial search. Finally, 28 studies with 3,227 participants were included. Among the 28 included studies, 20 studies were controlled studies, two of which were randomized controlled trials. The other eight studies were before/after surveys, without controls. Most of the studies were of moderate or low quality. Five broad categories of outcomes were identified in this study: 1) medical errors or patient safety, 2) health care workers’ quality of working life (e.g. reduced fatigue, discomfort, workload, pain and injury), 3) user performance (e.g., efficiency or accuracy), 4) health care workers’ attitudes towards the interventions(e.g., satisfaction and preference), and 5) economic evaluations. Conclusion The results showed that the interventions positively affected the outcomes of health care workers. Few studies considered the financial merits of these interventions. Most of the included studies were of moderate quality. This review highlights the need

  3. Some Challenges in the Design of Human-Automation Interaction for Safety-Critical Systems

    NASA Technical Reports Server (NTRS)

    Feary, Michael S.; Roth, Emilie

    2014-01-01

    Increasing amounts of automation are being introduced to safety-critical domains. While the introduction of automation has led to an overall increase in reliability and improved safety, it has also introduced a class of failure modes, and new challenges in risk assessment for the new systems, particularly in the assessment of rare events resulting from complex inter-related factors. Designing successful human-automation systems is challenging, and the challenges go beyond good interface development (e.g., Roth, Malin, & Schreckenghost 1997; Christoffersen & Woods, 2002). Human-automation design is particularly challenging when the underlying automation technology generates behavior that is difficult for the user to anticipate or understand. These challenges have been recognized in several safety-critical domains, and have resulted in increased efforts to develop training, procedures, regulations and guidance material (CAST, 2008, IAEA, 2001, FAA, 2013, ICAO, 2012). This paper points to the continuing need for new methods to describe and characterize the operational environment within which new automation concepts are being presented. We will describe challenges to the successful development and evaluation of human-automation systems in safety-critical domains, and describe some approaches that could be used to address these challenges. We will draw from experience with the aviation, spaceflight and nuclear power domains.

  4. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    NASA Astrophysics Data System (ADS)

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-03-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  5. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States.

    PubMed

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-01-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects' affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain's motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID:26996254

  6. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    PubMed Central

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-01-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID:26996254

  7. Factors affecting yield and safety of protein production from cassava by Cephalosporium eichhorniae

    SciTech Connect

    Mikami, Y.; Gregory, K.F.; Levadoux, W.L.; Balagopalan, C.; Whitwill, S.T.

    1982-01-01

    The properties of C. eichhorniae 152 (ATCC 38255) affecting protein production from cassava carbohydrate, for use as an animal feed, were studied. This strain is a true thermophile, showing optimum growth at 45-47 degrees, maximum protein yield at 45 degrees, and no growth at 25 degrees. It has an optimum pH of approximately 3.8 and is obligately acidophilic, being unable to sustain growth at pH of more than or equal to 6.0 in a liquid medium, or pH of more than or equal to 7.0 on solid media. The optimum growth conditions of pH 3.8 and 45 degrees were strongly inhibitive to potential contaminants. It rapidly hydrolyzed cassava starch. It did not utilize sucrose, but approximately 16% of the small sucrose component of cassava was chemically hydrolyzed during the process. Growth with cassava meal (50 g/l) was complete in approximately 20 h, yielding 22.5 g/l (dry biomass), containing 41% crude protein (48-50% crude protein in the mycelium) and 31% true protein (7.0 g/l). Resting and germinating spores (10 to the power of 6 - 10 to the power of 8 per animal) injected by various routes into normal and gamma-irradiated 6-week-old mice and 7-day-old chickens failed to initiate infections.

  8. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective.

    PubMed

    de Borst, Aline W; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations. PMID:26029133

  9. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective.

    PubMed

    de Borst, Aline W; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations.

  10. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective

    PubMed Central

    de Borst, Aline W.; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations. PMID:26029133

  11. Safety-Information-Driven Human Mobility Patterns with Metapopulation Epidemic Dynamics

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Cao, Lang; Suzuki, Hideyuki; Aihara, Kazuyuki

    2012-11-01

    With the help of mass media, people receive information concerning the status of an infectious disease to guide their mobility. Herein, we develop a theoretical framework to investigate the safety-information-driven human mobility with metapopulation epidemic dynamics. Individuals respond to the safety information of a city by taking safe moves (passing cities with a more number of healthy individuals) or unsafe moves (passing cities with a less number of healthy individuals). Our findings show that the critical threshold depends on mobility in such a way that personal execution of safe moves unexpectedly promotes the global spread of a disease, while unsafe moves counterintuitively cause a locally, relatively small outbreak size. Our analysis underlines the role of safety consideration in the spatial spread of an infectious disease with clear implications for the model of mobility driven by individuals' benefit.

  12. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  13. Industry Initiated Core Safety Attributes for Human Spaceflight for the 7th IAASS Conference

    NASA Technical Reports Server (NTRS)

    Mango, Edward J.

    2014-01-01

    Now that the NASA Commercial Crew Program (CCP) is beginning its full certification contract for crew transportation to the International Space Station (ISS), is it time for industry to embrace a minimum set of core safety attributes? Those attributes can then be evolved into an industry-led set of basic safety standards and requirements. After 50 years of human space travel sponsored by governments, there are two basic conditions that now exist within the international space industry. The first, there is enough of a space-faring history to encourage the space industry to design, develop and operate human spaceflight systems without government contracts for anything other than services. Second, industry is capable of defining and enforcing a set of industry-based safety attributes and standards for human spaceflight to low-Earth orbit (LEO). This paper will explore both of these basic conditions with a focus on the safety attributes and standards. In the United States, the Federal Aviation Administration (FAA) is now starting to dialogue with industry about the basic safety principles and attributes needed for potential future regulatory oversight. This process is not yet formalized and will take a number of years once approval is given to move forward. Therefore, throughout the next few years, it is an excellent time and opportunity for industry to collaborate together and develop the core set of attributes and standards. As industry engages and embraces a common set of safety attributes, then government agencies, like the FAA and NASA can use that industry-based product to strengthen their efforts on a safe commercial spaceflight foundation for the future. As the commercial space industry takes the lead role in establishing core safety attributes, and then enforcing those attributes, the entire planet can move away from governmental control of design and development and let industry expand safe and successful space operations in LEO. At that point the

  14. The Human Bathtub: Safety and Risk Predictions Including the Dynamic Probability of Operator Errors

    SciTech Connect

    Duffey, Romney B.; Saull, John W.

    2006-07-01

    Reactor safety and risk are dominated by the potential and major contribution for human error in the design, operation, control, management, regulation and maintenance of the plant, and hence to all accidents. Given the possibility of accidents and errors, now we need to determine the outcome (error) probability, or the chance of failure. Conventionally, reliability engineering is associated with the failure rate of components, or systems, or mechanisms, not of human beings in and interacting with a technological system. The probability of failure requires a prior knowledge of the total number of outcomes, which for any predictive purposes we do not know or have. Analysis of failure rates due to human error and the rate of learning allow a new determination of the dynamic human error rate in technological systems, consistent with and derived from the available world data. The basis for the analysis is the 'learning hypothesis' that humans learn from experience, and consequently the accumulated experience defines the failure rate. A new 'best' equation has been derived for the human error, outcome or failure rate, which allows for calculation and prediction of the probability of human error. We also provide comparisons to the empirical Weibull parameter fitting used in and by conventional reliability engineering and probabilistic safety analysis methods. These new analyses show that arbitrary Weibull fitting parameters and typical empirical hazard function techniques cannot be used to predict the dynamics of human errors and outcomes in the presence of learning. Comparisons of these new insights show agreement with human error data from the world's commercial airlines, the two shuttle failures, and from nuclear plant operator actions and transient control behavior observed in transients in both plants and simulators. The results demonstrate that the human error probability (HEP) is dynamic, and that it may be predicted using the learning hypothesis and the minimum

  15. Analysis of human factors effects on the safety of transporting radioactive waste materials: Technical report

    SciTech Connect

    Abkowitz, M.D.; Abkowitz, S.B.; Lepofsky, M.

    1989-04-01

    This report examines the extent of human factors effects on the safety of transporting radioactive waste materials. It is seen principally as a scoping effort, to establish whether there is a need for DOE to undertake a more formal approach to studying human factors in radioactive waste transport, and if so, logical directions for that program to follow. Human factors effects are evaluated on driving and loading/transfer operations only. Particular emphasis is placed on the driving function, examining the relationship between human error and safety as it relates to the impairment of driver performance. Although multi-modal in focus, the widespread availability of data and previous literature on truck operations resulted in a primary study focus on the trucking mode from the standpoint of policy development. In addition to the analysis of human factors accident statistics, the report provides relevant background material on several policies that have been instituted or are under consideration, directed at improving human reliability in the transport sector. On the basis of reported findings, preliminary policy areas are identified. 71 refs., 26 figs., 5 tabs.

  16. Aviation Safety: Modeling and Analyzing Complex Interactions between Humans and Automated Systems

    NASA Technical Reports Server (NTRS)

    Rungta, Neha; Brat, Guillaume; Clancey, William J.; Linde, Charlotte; Raimondi, Franco; Seah, Chin; Shafto, Michael

    2013-01-01

    The on-going transformation from the current US Air Traffic System (ATS) to the Next Generation Air Traffic System (NextGen) will force the introduction of new automated systems and most likely will cause automation to migrate from ground to air. This will yield new function allocations between humans and automation and therefore change the roles and responsibilities in the ATS. Yet, safety in NextGen is required to be at least as good as in the current system. We therefore need techniques to evaluate the safety of the interactions between humans and automation. We think that current human factor studies and simulation-based techniques will fall short in front of the ATS complexity, and that we need to add more automated techniques to simulations, such as model checking, which offers exhaustive coverage of the non-deterministic behaviors in nominal and off-nominal scenarios. In this work, we present a verification approach based both on simulations and on model checking for evaluating the roles and responsibilities of humans and automation. Models are created using Brahms (a multi-agent framework) and we show that the traditional Brahms simulations can be integrated with automated exploration techniques based on model checking, thus offering a complete exploration of the behavioral space of the scenario. Our formal analysis supports the notion of beliefs and probabilities to reason about human behavior. We demonstrate the technique with the Ueberligen accident since it exemplifies authority problems when receiving conflicting advices from human and automated systems.

  17. Human factors engineering design review acceptance criteria for the safety parameter display

    SciTech Connect

    McGevna, V.; Peterson, L.R.

    1981-10-02

    This report contains human factors engineering design review acceptance criteria developed by the Human Factors Engineering Branch (HFEB) of the Nuclear Regulatory Commission (NRC) to use in evaluating designs of the Safety Parameter Display System (SPDS). These criteria were developed in response to the functional design criteria for the SPDS defined in NUREG-0696, Functional Criteria for Emergency Response Facilities. The purpose of this report is to identify design review acceptance criteria for the SPDS installed in the control room of a nuclear power plant. Use of computer driven cathode ray tube (CRT) displays is anticipated. General acceptance criteria for displays of plant safety status information by the SPDS are developed. In addition, specific SPDS review criteria corresponding to the SPDS functional criteria specified in NUREG-0696 are established.

  18. Biosafety Test for Plant Growth-Promoting Bacteria: Proposed Environmental and Human Safety Index (EHSI) Protocol

    PubMed Central

    Vílchez, Juan I.; Navas, Alfonso; González-López, Jesús; Arcos, Susana C.; Manzanera, Maximino

    2016-01-01

    Plant growth-promoting bacteria (PGPB) colonize plants and enhance their growth by different mechanisms. Some of these microorganisms may represent a potential threat to human, animal or plant health; however, their use might be approved in parts of Europe if they have been recommended as plant growth enhancers. The current regulatory framework has resulted in a fragmented, contradictory system, and there is an urgent need to establish harmonized protocols for the predictability, efficiency, consistency and especially the safety of PGPB for human and animal health and for the environment. In response to current efforts to update biosafety policies and provide alternative methods to replace the use of vertebrate animals, we propose a panel of tests and an evaluation system to reliably determine the biosafety of bacterial strains used as PGPB. Based on the results of different tests, we propose a scoring system to evaluate the safety of candidates for PGPB within the limitations of the assays used. PMID:26779168

  19. Human T-lymphotropic virus and transfusion safety: does one size fit all?

    PubMed

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Facco, Giuseppina; Catalano, Liviana; Piccinini, Vanessa; Liumbruno, Giancarlo Maria; Grazzini, Giuliano

    2016-01-01

    Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries. PMID:26388300

  20. Mutagenesis within human FcepsilonRIalpha differentially affects human and murine IgE binding.

    PubMed

    Mackay, Graham A; Hulett, Mark D; Cook, Justin P D; Trist, Halina M; Henry, Alistair J; McDonnell, James M; Beavil, Andrew J; Beavil, Rebecca L; Sutton, Brian J; Hogarth, P Mark; Gould, Hannah J

    2002-02-15

    Soluble fragments of the alpha-chain of FcepsilonRI, the high-affinity receptor for IgE, compete with membrane-bound receptors for IgE and may thus provide a means to combat allergic responses. Mutagenesis within FcepsilonRIalpha is used in this study, in conjunction with the crystal structure of the FcepsilonRIalpha/IgE complex, to define the relative importance of specific residues within human FcepsilonRIalpha for IgE binding. We have also compared the effects of these mutants on binding to both human and mouse IgE, with a view to evaluating the mouse as an appropriate model for the analysis of future agents designed to mimic the human FcepsilonRIalpha and attenuate allergic disease. Three residues within the C-C' region of the FcepsilonRIalpha2 domain and two residues within the alpha2 proximal loops of the alpha1 domain were selected for mutagenesis and tested in binding assays with human and mouse IgE. All three alpha2 mutations (K117D, W130A, and Y131A) reduced the affinity of human IgE binding to different extents, but K117D had a far more pronounced effect on mouse IgE binding, and although Y131A had little effect, W130A modestly enhanced binding to mouse IgE. The mutations in alpha1 (R15A and F17A) diminished binding to both human and mouse IgE, with these effects most likely caused by disruption of the alpha1/alpha2 interface. Our results demonstrate that the effects of mutations in human FcepsilonRIalpha on mouse IgE binding, and hence the inhibitory properties of human receptor-based peptides assayed in rodent models of allergy, may not necessarily reflect their activity in a human IgE-based system.

  1. The brain's emotional foundations of human personality and the Affective Neuroscience Personality Scales.

    PubMed

    Davis, Kenneth L; Panksepp, Jaak

    2011-10-01

    Six of the primary-process subcortical brain emotion systems - SEEKING, RAGE, FEAR, CARE, GRIEF and PLAY - are presented as foundational for human personality development, and hence as a potentially novel template for personality assessment as in the Affective Neurosciences Personality Scales (ANPS), described here. The ANPS was conceptualized as a potential clinical research tool, which would help experimentalists and clinicians situate subjects and clients in primary-process affective space. These emotion systems are reviewed in the context of a multi-tiered framing of consciousness spanning from primary affect, which encodes biological valences, to higher level tertiary (thought mediated) processing. Supporting neuroscience research is presented along with comparisons to Cloninger's Temperament and Character Inventory and the Five Factor Model (FFM). Suggestions are made for grounding the internal structure of the FFM on the primal emotional systems recognized in affective neuroscience, which may promote substantive dialog between human and animal research traditions. Personality is viewed in the context of Darwinian "continuity" with the inherited subcortical brain emotion systems being foundational, providing major forces for personality development in both humans and animals, and providing an affective infrastructure for an expanded five factor descriptive model applying to normal and clinical human populations as well as mammals generally. Links with ontogenetic and epigenetic models of personality development are also presented. Potential novel clinical applications of the CARE maternal-nurturance system and the PLAY system are also discussed.

  2. Examining dog-human play: the characteristics, affect, and vocalizations of a unique interspecific interaction.

    PubMed

    Horowitz, Alexandra; Hecht, Julie

    2016-07-01

    Despite the growing interest in research on the interaction between humans and dogs, only a very few research projects focus on the routines between dogs and their owners. In this study, we investigated one such routine: dog-human play. Dyadic interspecific play is known to be a common interaction between owner and charge, but the details of what counts as play have not been thoroughly researched. Similarly, though people represent that "play" is pleasurable, no study has yet undertaken to determine whether different forms of play are associated with different affective states. Thus, we aimed to generate an inventory of the forms of dyadic play, the vocalizations within play, and to investigate the relationship of affect to elements of play. Via a global citizen science project, we solicited videotapes of dog-human play sessions from dog owners. We coded 187 play bouts via frame-by-frame video playback. We then assessed the relationship between various intra-bout variables and owner affect (positive or neutral) during play (dog affect was overwhelmingly positive). Amount of physical contact ("touch"), level of activity of owner ("movement"), and physical closeness of dog-owner dyad ("proximity") were highly correlated with positive affect. Owner vocalizations were found to contain different elements in positive- and neutral-affect play. One novel category of play, "tease", was found. We conclude that not all play is created equal: the experience of play to the owner participant is strongly related to a few identifiable characteristics of the interaction.

  3. Human-System Safety Methods for Development of Advanced Air Traffic Management Systems

    SciTech Connect

    Nelson, W.R.

    1999-05-24

    The Idaho National Engineering and Environmental Laboratory (INEEL) is supporting the National Aeronautics and Space Administration in the development of advanced air traffic management (ATM) systems as part of the Advanced Air Transportation Technologies program. As part of this program INEEL conducted a survey of human-system safety methods that have been applied to complex technical systems, to identify lessons learned from these applications and provide recommendations for the development of advanced ATM systems. The domains that were surveyed included offshore oil and gas, commercial nuclear power, commercial aviation, and military. The survey showed that widely different approaches are used in these industries, and that the methods used range from very high-level, qualitative approaches to very detailed quantitative methods such as human reliability analysis (HRA) and probabilistic safety assessment (PSA). In addition, the industries varied widely in how effectively they incorporate human-system safety assessment in the design, development, and testing of complex technical systems. In spite of the lack of uniformity in the approaches and methods used, it was found that methods are available that can be combined and adapted to support the development of advanced air traffic management systems.

  4. [Theoretical analysis of factors affecting heat exchange stability of human body with environment].

    PubMed

    Wu, Q; Wang, X

    1998-06-01

    Life could not be normal without the heat produced by metabolism of human body being transmitted into environment. This paper discussed the ways of heat exchange of human body with the environment, and analyzed their effects on the stability of heat exchange theoretically. In addition, factors that affects the stability of heat exchange were studied. The results indicate that the environmental temperature is the most important factor.

  5. Safety of human blood products: inactivation of retroviruses by heat treatment at 60 degrees C.

    PubMed

    Hilfenhaus, J; Mauler, R; Friis, R; Bauer, H

    1985-04-01

    Acquired immune deficiency syndrome (AIDS) can be transferred to patients by blood transfusions or human blood preparations, such as cryoprecipitates or factor VIII concentrates. Retroviruses have been discussed as infectious AIDS agents and more recently human T-lymphotropic retroviruses designated as HTLV type III and LAV (lymphadenopathy-associated virus) have been isolated from AIDS patients. Whether heat treatment at 60 degrees C (pasteurization) of liquid human plasma protein preparations inactivates retroviruses was therefore investigated. Pasteurization had already been included in the routine manufacturing process of human plasma protein preparations in order to guarantee safety with regard to hepatitis B. Since high titer preparations of human retroviruses were not available, heat inactivation was studied using Rous sarcoma virus added to the various plasma protein preparations tested. This retrovirus which was obtained in preparations of 6.0 log10 FFU/ml was shown to be at least as heat stable as two mammalian retroviruses studied, i.e., feline and simian sarcoma virus. In all of eight different plasma protein preparations tested, Rous sarcoma virus was completely inactivated after a heat treatment lasting no longer than 4 hr. It is thus concluded that pasteurization of liquid plasma protein preparations at 60 degrees C over a period of 10 hr must confer safety to these products with respect to AIDS, provided that the AIDS agents are retroviruses of comparable heat stability as Rous sarcoma virus and the mammalian retroviruses tested.

  6. Affective Education: A Teacher's Manual to Promote Student Self-Actualization and Human Relations Skills.

    ERIC Educational Resources Information Center

    Snyder, Thomas R.

    This teacher's manual presents affective education as a program to promote student self-actualization and human relations skills. Abraham Maslow's hierarchy of needs and Erik Erikson's life stages of psychosocial development form the conceptual base for this program. The goals and objectives of this manual are concerned with problem-solving…

  7. Definition and Measurement in the Affective Domain: Appreciation of Human Accomplishments.

    ERIC Educational Resources Information Center

    Campbell, Paul B.; Beers, Joan S.

    The first three levels of the taxonomy in the affective domain guided the development of two inventories--the Pennsylvania Inventory of Cultural Appreciations (PICA) for 11th graders and Things People Do (TPD) for 5th graders--to measure appreciation of human accomplishments in seven areas: politics, sciences, sports, literature, visual arts,…

  8. The Design of Transportation Equipment in Terms of Human Capabilities. The Role of Engineering Psychology in Transport Safety.

    ERIC Educational Resources Information Center

    McFarland, Ross A.

    Human factors engineering is considered with regard to the design of safety factors for aviation and highway transportation equipment. Current trends and problem areas are identified for jet air transportation and for highway transportation. Suggested solutions to transportation safety problems are developed by applying the techniques of human…

  9. Does human migration affect international trade? A complex-network perspective.

    PubMed

    Fagiolo, Giorgio; Mastrorillo, Marina

    2014-01-01

    This paper explores the relationships between international human migration and merchandise trade, using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960-2000. Next, we ask whether the position of any pair of countries in the migration network affects their bilateral trade flows. We show that: (i) both weighted and binary versions of the networks of international migration and trade are strongly correlated; (ii) such correlations can be mostly explained by country economic/demographic size and geographical distance; and (iii) pairs of countries that are more central in the international-migration network trade more. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries but also by their relative embeddedness in the complex web of corridors making up the network of international human migration.

  10. Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies.

    PubMed

    Codd, Ellen E; Ng, Hanna H; McFarlane, Claire; Riccio, Edward S; Doppalapudi, Rupa; Mirsalis, Jon C; Horton, R John; Gonzalez, Armando E; Garcia, H Hugo; Gilman, Robert H

    2015-01-01

    A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.

  11. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery.

    PubMed

    Crouzier, David; Dabouis, Vincent; Gentilhomme, Edgar; Vignal, Rodolphe; Bourbon, Fréderic; Fauvelle, Florence; Debouzy, Jean-Claude

    2014-01-01

    LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m(2)), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, (1)H-NMR HRMAS metabolomics, (13)C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified. PMID:24757560

  12. Proteome Analysis of Human Sebaceous Follicle Infundibula Extracted from Healthy and Acne-Affected Skin

    PubMed Central

    Bek-Thomsen, Malene; Lomholt, Hans B.; Scavenius, Carsten; Enghild, Jan J.; Brüggemann, Holger

    2014-01-01

    Acne vulgaris is a very common disease of the pilosebaceous unit of the human skin. The pathological processes of acne are not fully understood. To gain further insight sebaceous follicular casts were extracted from 18 healthy and 20 acne-affected individuals by cyanoacrylate-gel biopsies and further processed for mass spectrometry analysis, aiming at a proteomic analysis of the sebaceous follicular casts. Human as well as bacterial proteins were identified. Human proteins enriched in acne and normal samples were detected, respectively. Normal follicular casts are enriched in proteins such as prohibitins and peroxiredoxins which are involved in the protection from various stresses, including reactive oxygen species. By contrast, follicular casts extracted from acne-affected skin contained proteins involved in inflammation, wound healing and tissue remodeling. Among the most distinguishing proteins were myeloperoxidase, lactotransferrin, neutrophil elastase inhibitor and surprisingly, vimentin. The most significant biological process among all acne-enriched proteins was ‘response to a bacterium’. Identified bacterial proteins were exclusively from Propionibacterium acnes. The most abundant P. acnes proteins were surface-exposed dermatan sulphate adhesins, CAMP factors, and a so far uncharacterized lipase in follicular casts extracted from normal as well as acne-affected skin. This is a first proteomic study that identified human proteins together with proteins of the skin microbiota in sebaceous follicular casts. PMID:25238151

  13. Human Infant Faces Provoke Implicit Positive Affective Responses in Parents and Non-Parents Alike

    PubMed Central

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H.; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors. PMID:24282537

  14. Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

    PubMed

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors.

  15. How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria

    PubMed Central

    Kwiatkowski, Dominic P.

    2005-01-01

    Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, α+ thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine. PMID:16001361

  16. Updating Human Factors Engineering Guidelines for Conducting Safety Reviews of Nuclear Power Plants

    SciTech Connect

    O, J.M.; Higgins, J.; Stephen Fleger - NRC

    2011-09-19

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. This paper describes the role of HFE guidelines in the safety review process and the content of the key HFE guidelines used. Then we will present the methodology used to develop HFE guidance and update these documents, and describe the current status of the update program.

  17. Excitotoxic food additives--relevance of animal studies to human safety.

    PubMed

    Olney, J W

    1984-01-01

    Evidence is reviewed supporting the view that excitotoxic food additives pose a significant hazard to the developing nervous system of young children. The following points are stressed: (1) although blood-brain barriers protect most central neurons from excitotoxins, certain brain regions lack such protection (a characteristic common to all vertebrate species); (2) regardless of species, it requires only a transient increase in blood excitotoxin levels for neurons in unprotected brain regions to be "silently" destroyed; (3) humans may be at particularly high risk for this kind of brain damage, since ingestion of a given amount of excitotoxin causes much higher blood excitotoxin levels in humans than in other species; (4) in addition to the heightened risk on a species basis, risk may be further increased for certain consumer sub-populations due to youth, disease or genetic factors; (5) despite these reasons for maintaining a wide margin of safety in the use of excitotoxins in foods, no safety margin is currently being observed, i.e., a comparative evaluation of animal (extensive) and human (limited) data supports the conclusion that excitotoxins, as used in foods today, may produce blood elevations high enough to cause damage to the nervous system of young children, damage which is not detectable at the time of occurrence but which may give rise to subtle disturbances in neuroendocrine function in adolescence and/or adulthood.

  18. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  19. Human factors and safety considerations of night-vision systems flight using thermal imaging systems

    NASA Astrophysics Data System (ADS)

    Rash, Clarence E.; Verona, Robert W.; Crowley, John S.

    1990-10-01

    Helmet Mounted Systems (HMS) must be lightweight, balanced and compatible with life support and head protection assemblies. This paper discusses the design of one particular HMS, the GEC Ferranti NITE-OP/NIGHTBIRD aviator's Night Vision Goggle (NVG) developed under contracts to the Ministry of Defence for all three services in the United Kingdom (UK) for Rotary Wing and fast jet aircraft. The existing equipment constraints, safety, human factor and optical performance requirements are discussed before the design solution is presented after consideration of these material and manufacturing options.

  20. On Space Exploration and Human Error: A Paper on Reliability and Safety

    NASA Technical Reports Server (NTRS)

    Bell, David G.; Maluf, David A.; Gawdiak, Yuri

    2005-01-01

    NASA space exploration should largely address a problem class in reliability and risk management stemming primarily from human error, system risk and multi-objective trade-off analysis, by conducting research into system complexity, risk characterization and modeling, and system reasoning. In general, in every mission we can distinguish risk in three possible ways: a) known-known, b) known-unknown, and c) unknown-unknown. It is probably almost certain that space exploration will partially experience similar known or unknown risks embedded in the Apollo missions, Shuttle or Station unless something alters how NASA will perceive and manage safety and reliability

  1. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans.

    PubMed

    Williams, G M; Kroes, R; Munro, I C

    2000-04-01

    Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption. Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with

  2. Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine

    PubMed Central

    Riede, O; Seifert, K; Oswald, D; Endmann, A; Hock, C; Winkler, A; Salguero, F J; Schroff, M; Croft, S L; Juhls, C

    2015-01-01

    The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine. PMID:25871827

  3. Effects of Virtual Human Appearance Fidelity on Emotion Contagion in Affective Inter-Personal Simulations.

    PubMed

    Volante, Matias; Babu, Sabarish V; Chaturvedi, Himanshu; Newsome, Nathan; Ebrahimi, Elham; Roy, Tania; Daily, Shaundra B; Fasolino, Tracy

    2016-04-01

    Realistic versus stylized depictions of virtual humans in simulated inter-personal situations and their ability to elicit emotional responses in users has been an open question for artists and researchers alike. We empirically evaluated the effects of near visually realistic vs. non-realistic stylized appearance of virtual humans on the emotional response of participants in a medical virtual reality system that was designed to educate users in recognizing the signs and symptoms of patient deterioration. In a between-subjects experiment protocol, participants interacted with one of three different appearances of a virtual patient, namely visually realistic, cartoon-shaded and charcoal-sketch like conditions in a mixed reality simulation. Emotional impact were measured via a combination of quantitative objective measures were gathered using skin Electrodermal Activity (EDA) sensors, and quantitative subjective measures such as the Differential Emotion Survey (DES IV), Positive and Negative Affect Schedule (PANAS), and Social Presence questionnaire. The emotional states of the participants were analyzed across four distinct time steps during which the medical condition of the virtual patient deteriorated (an emotionally stressful interaction), and were contrasted to a baseline affective state. Objective EDA results showed that in all three conditions, male participants exhibited greater levels of arousal as compared to female participants. We found that negative affect levels were significantly lower in the visually realistic condition, as compared to the stylized appearance conditions. Furthermore, in emotional dimensions of interest-excitement, surprise, anger, fear and guilt participants in all conditions responded similarly. However, in social emotional constructs of shyness, presence, perceived personality, and enjoyment-joy, we found that participants responded differently in the visually realistic condition as compared to the cartoon and sketch conditions. Our

  4. Human-based systems in drug and chemical safety testing--toward replacement, the 'single R'.

    PubMed

    Coleman, Robert A

    2014-12-01

    The Three Rs was a concept originally conceived as a means of reducing the suffering of laboratory animals that are used largely in identifying any potential safety issues with chemicals to which humans may be exposed. However, with growing evidence of the shortcomings of laboratory animal testing to reliably predict human responsiveness to such chemicals, questions are now being asked as to whether it is appropriate to use animals as human surrogates at all. This raises the question of whether, of the original Three Rs, two--Reduction and Refinement--are potentially redundant, and whether, instead, we should concentrate on the third R: Replacement. And if this is the best way forward, it is inevitable that this R should be based firmly on human biology. The present review outlines the current state-of-the-art regarding our access to human biology through in vitro, in silico and in vivo technologies, identifying strengths, weaknesses and opportunities, and goes on to address the prospect of achieving a single R, with some suggestions as to how to progress toward this goal.

  5. Safety evaluation of the human-identical milk monosaccharide, l-fucose.

    PubMed

    Choi, Sharon S H; Lynch, Barry S; Baldwin, Nigel; Dakoulas, Emily W; Roy, Shambhu; Moore, Carey; Thorsrud, Bjorn A; Röhrig, Christoph H

    2015-06-01

    l-Fucose is a natural monosaccharide present in mammals where it is found predominantly as an O-glycosidically linked component of glycoproteins, glycolipids, and oligosaccharides. It is also present in its free form in human breast milk (human milk monosaccharide). l-Fucose plays important roles in the development of the immune and nervous systems and is involved in cognitive function and memory formation. The human-identical milk monosaccharide l-fucose is therefore proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of l-fucose, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. l-Fucose was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 1% (highest level tested), corresponding to doses of 516 and 665 mg/kg bw/day in males and females, respectively. l-Fucose was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of l-fucose in infant formula and as a food ingredient at levels equivalent to those present in human breast milk.

  6. Aspergillus flavus genomics: gateway to human and animal health, food safety, and crop resistance to diseases.

    PubMed

    Yu, Jiujiang; Cleveland, Thomas E; Nierman, William C; Bennett, Joan W

    2005-12-01

    Aspergillus flavus is an imperfect filamentous fungus that is an opportunistic pathogen causing invasive and non-invasive aspergillosis in humans, animals, and insects. It also causes allergic reactions in humans. A. flavus infects agricultural crops and stored grains and produces the most toxic and potent carcinogic metabolites such as aflatoxins and other mycotoxins. Breakthroughs in A. flavus genomics may lead to improvement in human health, food safety, and agricultural economy. The availability of A. flavus genomic data marks a new era in research for fungal biology, medical mycology, agricultural ecology, pathogenicity, mycotoxin biosynthesis, and evolution. The availability of whole genome microarrays has equipped scientists with a new powerful tool for studying gene expression under specific conditions. They can be used to identify genes responsible for mycotoxin biosynthesis and for fungal infection in humans, animals and plants. A. flavus genomics is expected to advance the development of therapeutic drugs and to provide information for devising strategies in controlling diseases of humans and other animals. Further, it will provide vital clues for engineering commercial crops resistant to fungal infection by incorporating antifungal genes that may prevent aflatoxin contamination of agricultural harvest. PMID:16499411

  7. Structural Design Requirements and Factors of Safety for Spaceflight Hardware: For Human Spaceflight. Revision A

    NASA Technical Reports Server (NTRS)

    Bernstein, Karen S.; Kujala, Rod; Fogt, Vince; Romine, Paul

    2011-01-01

    This document establishes the structural requirements for human-rated spaceflight hardware including launch vehicles, spacecraft and payloads. These requirements are applicable to Government Furnished Equipment activities as well as all related contractor, subcontractor and commercial efforts. These requirements are not imposed on systems other than human-rated spacecraft, such as ground test articles, but may be tailored for use in specific cases where it is prudent to do so such as for personnel safety or when assets are at risk. The requirements in this document are focused on design rather than verification. Implementation of the requirements is expected to be described in a Structural Verification Plan (SVP), which should describe the verification of each structural item for the applicable requirements. The SVP may also document unique verifications that meet or exceed these requirements with NASA Technical Authority approval.

  8. Integrating Safety and Lessons-Learned Data with Human Performance for Successful Management and Oversight

    SciTech Connect

    Prevette, S.S.; Bilson, H.E.

    2008-07-01

    This paper documents the improvements Fluor Hanford, Inc. (Fluor Hanford) is making in analyzing and using safety-related and lessons-learned data in cleaning up the U.S. Department of Energy's (DOE's) site at Hanford in southeastern Washington state. Results of the application of Statistical Process Control (SPC) and Dashboards to support planning and decision making have been shared at past Waste Management conferences. Recently, Fluor Hanford has implemented and refined a process called the 'Data Analysis Working Group' to integrate data from several sources, including opinions from subject-matter experts. The process also includes a risk-ranking tool used to prioritize potential risks and past problems for management and oversight of the Hanford cleanup. Human Performance and Lessons Learned information also is included in this process. Fluor Hanford has applied SPC in a non-traditional (that is non-manufacturing) manner. Dr. Shewhart's 75-year-old control-chart methodologies have been updated to modern data processing, but are still founded on his sound, tried and true principles. These methods are playing a key role in safety and quality at Hanford. The performance-indicator system used by Fluor Hanford has been featured by several professional societies in their publications, primarily the American Society of Safety Engineers and the American Society for Quality. The system also has been featured in past Waste Management conferences. Eleven years ago, Fluor Hanford's statistician produced 300 data files and accompanying charts a month. Today, those numbers exceed 3,000 a month, almost one chart for every employee. This activity also includes entering data for approximately 500 safety inspections each month. The challenge is in effectively analyzing and prioritizing this information and providing it to senior management to make pro-active decisions and policies. That challenge is being met by Fluor's Data Analysis Working Group process. (authors)

  9. Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor.

    PubMed

    Pettengell, Ruth; Bias, Peter; Mueller, Udo; Lang, Nicole

    2016-06-01

    The recombinant human granulocyte colony-stimulating factor (G-CSF) known as filgrastim (Tevagrastim(®), Ratiograstim(®), Biograstim(®)) in Europe (approved in 2008) and tbo-filgrastim (Granix(®)) in the USA (approved in 2012; Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel) is indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. This article presents pooled clinical data for tbo-filgrastim compared with Neupogen(®) (Amgen, Thousand Oaks, CA, USA) as well as tbo-filgrastim post-marketing safety data. The safety and efficacy of tbo-filgrastim were evaluated in three phase III studies in 677 patients receiving myelosuppressive chemotherapy and study drug (348 patients with breast cancer, 237 with lung cancer, 92 with non-Hodgkin lymphoma). In each study, the efficacy of tbo-filgrastim was similar to that of Neupogen. Overall, 633 (93.5 %) patients receiving the study drug experienced 6093 treatment-emergent adverse events (AEs), most of which were related to chemotherapy. Adverse events related to the study drug (tbo-filgrastim or Neupogen) were experienced by 185 (27.3 %) patients; 19 (2.8 %) had severe drug-related AEs, 5 (0.7 %) had drug-related serious AEs, and 6 (0.9 %) discontinued the study due to drug-related AEs. Overall, the most common drug-related AEs were bone pain (7.1 %), myalgia (4.0 %), and asthenia (4.4 %). The post-marketing safety profile of tbo-filgrastim was consistent with that observed during the clinical studies. The availability of tbo-filgrastim, a G-CSF with safety and efficacy comparable to those of Neupogen, provides physicians with an alternative treatment option for supportive care of patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. PMID:26780505

  10. Short-term safety evaluation of processed calcium montmorillonite clay (NovaSil) in humans.

    PubMed

    Wang, J-S; Luo, H; Billam, M; Wang, Z; Guan, H; Tang, L; Goldston, T; Afriyie-Gyawu, E; Lovett, C; Griswold, J; Brattin, B; Taylor, R J; Huebner, H J; Phillips, T D

    2005-03-01

    NovaSil clay (NS) provides significant protection from the adverse effects of aflatoxins (AFs) in multiple animal species by decreasing bioavailability from the gastrointestinal tract. It is postulated that NS clay can be safely added to human diets to diminish exposure and health risks from AF contaminated food. To determine the safety and tolerance of NS in humans and establish dosimetry protocols for long-term efficacy studies, a randomized and double-blinded phase I clinical trial was conducted. Volunteers (20-45 yr in age), were clinically screened for confirmation of their health status. Fifty subjects (23 males and 27 females) were randomly divided into two groups: The low-dose group received nine capsules containing 1.5 g/day, and the high-dose group received nine capsules containing 3.0 g/day for a period of 2?wk. NS capsules were manufactured in the same color and size and were distributed to each participant three times a day at designated sites where follow-up was taken to record any side effects and complaints. Blood and urine samples were collected before and after the study for laboratory analysis. All participants completed the trial and compliance was 99.1%. Mild GI effects were reported in some participants. Symptoms included abdominal pain (6%, 3/50), bloating (4%, 2/50), constipation (2%, 1/50), diarrhea (2%, 1/50), and flatulence (8%, 4/50). No statistical significance was found between the two groups for these adverse effects (p > 0.25). No significant differences were shown in hematology, liver and kidney function, electrolytes, vitamins A and E, and minerals in either group. These results demonstrate the relative safety of NS clay in human subjects and will serve as a basis for long-term human trials in populations at high risk for aflatoxicosis. PMID:16019795

  11. Low-frequency sound affects active micromechanics in the human inner ear

    PubMed Central

    Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

    2014-01-01

    Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing. PMID:26064536

  12. Does Human Migration Affect International Trade? A Complex-Network Perspective

    PubMed Central

    Fagiolo, Giorgio; Mastrorillo, Marina

    2014-01-01

    This paper explores the relationships between international human migration and merchandise trade using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960–2000. Next, we ask whether pairs of countries that are more central in the migration network trade more. We show that: (i) the networks of international migration and trade are strongly correlated, and such correlation can be mostly explained by country economic/demographic size and geographical distance; (ii) centrality in the international-migration network boosts bilateral trade; (iii) intensive forms of country centrality are more trade enhancing than their extensive counterparts. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries, but also by their relative embeddedness in the complex web of corridors making up the network of international human migration. PMID:24828376

  13. A Real-time Evaluation of Human-based Approaches to Safety Testing: What We Can Do Now (TDS)

    EPA Science Inventory

    Despite ever-increasing efforts in early safety assessment in all industries, there are still many chemicals that prove toxic in humans. While greater use of human in vitro test methods may serve to reduce this problem, the formal validation process applied to such tests represen...

  14. Practical Applications of Cosmic Ray Science: Spacecraft, Aircraft, Ground-Based Computation and Control Systems, and Human Health and Safety

    NASA Technical Reports Server (NTRS)

    Atwell, William; Koontz, Steve; Normand, Eugene

    2012-01-01

    Three twentieth century technological developments, 1) high altitude commercial and military aircraft; 2) manned and unmanned spacecraft; and 3) increasingly complex and sensitive solid state micro-electronics systems, have driven an ongoing evolution of basic cosmic ray science into a set of practical engineering tools needed to design, test, and verify the safety and reliability of modern complex technological systems. The effects of primary cosmic ray particles and secondary particle showers produced by nuclear reactions with the atmosphere, can determine the design and verification processes (as well as the total dollar cost) for manned and unmanned spacecraft avionics systems. Similar considerations apply to commercial and military aircraft operating at high latitudes and altitudes near the atmospheric Pfotzer maximum. Even ground based computational and controls systems can be negatively affected by secondary particle showers at the Earth s surface, especially if the net target area of the sensitive electronic system components is large. Finally, accumulation of both primary cosmic ray and secondary cosmic ray induced particle shower radiation dose is an important health and safety consideration for commercial or military air crews operating at high altitude/latitude and is also one of the most important factors presently limiting manned space flight operations beyond low-Earth orbit (LEO). In this paper we review the discovery of cosmic ray effects on the performance and reliability of microelectronic systems as well as human health and the development of the engineering and health science tools used to evaluate and mitigate cosmic ray effects in ground-based atmospheric flight, and space flight environments. Ground test methods applied to microelectronic components and systems are used in combinations with radiation transport and reaction codes to predict the performance of microelectronic systems in their operating environments. Similar radiation transport

  15. Assessment of Human Safety and Thermal Comfort in High-Temperature Environment: CFD and Human Thermoregulation Model

    NASA Astrophysics Data System (ADS)

    Xuefeng, Han; Wenguo, Weng; Shifei, Shen

    2010-05-01

    The safety and the thermal comfort of victims and firefighters are important in the building fires, which are a little dependent on the occupant fatalities. In order to investigate the effects of the dangerous environment on human body in fires, numerical calculation of the heat transfer and human thermoregulation are presented in this paper. The numerical manikins coupled with human thermal models were proved as powerful tools for visualizing thermal comfort. The two-node model by Gagge and multi-code thermoregulation models were investigated, and the Gagge's model was coupled with the CFD for high-temperature environment simulation, with which a numerical manikin was built. During the simulation, temperatures of skin and core compartment of Computer Simulated Person (CPS) were recorded respectively, and the Predicted Mean Vote index values were counted. The thermal load on skin is much higher than neutral cases and the skin can be burnt in minutes if no protection and heat abstraction methods were introduced. Though existing models can predict thermal comfort in general indoor environment, they are not suitable in predicting the thermal comfort with high-temperature cases. It was suggested that more research combining CFD coupling thermoregulation models with thermal manikin experiment are needed.

  16. Water content and apparent stiffness of non-caries versus caries-affected human dentin.

    PubMed

    Ito, Shuichi; Saito, Takashi; Tay, Franklin R; Carvalho, Ricardo M; Yoshiyama, Masahiro; Pashley, David H

    2005-01-15

    Caries-affected dentin contains less mineral and more water than surrounding normal dentin. Such dentin should be less stiff and should shrink more than normal dentin when dried. The purpose of this study was to test the relationships between the stiffness, shrinkage, and water content of caries-affected versus normal dentin. Extracted human carious third molars were stained with caries-detector dye and the occlusal surfaces ground down until only caries-affected dentin remained, surrounded by normal dentin. Dentin disks were prepared from these crowns placed in a aluminum well positioned under a modified thermal mechanical analyzer. Changes in specimen height and stiffness were measured following drying or static loading in both caries-affected and surrounding normal dentin. Core samples of these two types of dentin were used to gravimetrically measure water content. Two-way ANOVA and regression analysis was used to test the relationship between shrinkage versus water content, stiffness versus water content, and stiffness versus shrinkage. Caries-affected dentin was found to be less stiff and contained more water than normal dentin (p < 0.05). Regression analysis revealed highly significant inverse relationships between stiffness and water content, and stiffness and shrinkage (p < 0.0005).

  17. 1981 NRC/BNL/IEEE standards workshop on human factors and nuclear safety. The man-machine interface and human reliability: an assessment and projection

    SciTech Connect

    Hall, R.E.; Fragola, J.R.; Luckas, W.J. Jr.

    1981-09-01

    The role of the human in the safety of nuclear power plant operations was addressed in a meeting held in Myrtle Beach, SC in August 1981. Presentation were made on Control Room reviews, safety parameter display systems, the integration of human factors in the entire design process, and the use of automated control features. A need was shown for the development of a taxonomy or model to structure future data gathering and the need for models and data to address the issue of cognitive behavior. The primary effect of this behavior on risk was identified. Discussion sessions on the human impact on reliability, and control room design and evaluation were included. (ACR)

  18. Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis

    PubMed Central

    Coelho, Pedro Luiz Spinelli; Calestini, Gustavo Lacerda da Silva; Alvo, Fernando Salgueiro; Freitas, Jefferson Michel de Moura; Castro, Paula Marcela Vilela; Konstantyner, Tulio

    2015-01-01

    Objective: To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Data source: Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Data synthesis: Fourteen studies were included. The most common adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: pain-risk difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). Conclusions: The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. PMID:26376359

  19. 4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro.

    PubMed Central

    Forsgren, A; Schlossman, S F; Tedder, T F

    1987-01-01

    Most antibacterial agents do not affect human lymphocyte function, but a few are inhibitory. In contrast, a pronounced increase in the incorporation of [3H]thymidine in the presence of 4-quinolones was observed in these studies. The uptake of [3H]thymidine into DNA (trichloroacetic acid precipitable) was significantly increased in phytohemagglutinin-stimulated human lymphocytes when they were exposed to eight new 4-quinolone derivatives, ciprofloxacin, norfloxacin, ofloxacin, A-56619, A-56620, amifloxacin, enoxacin, and pefloxacin, at 1.6 to 6.25 micrograms/ml for 5 days. Four less antibacterially active 4-quinolones (nalidixic acid, cinoxacin, flumequine, and pipemidic acid) stimulated [3H]thymidine incorporation only at higher concentrations or not at all. Kinetic studies showed that incorporation of [3H]thymidine was not affected or slightly inhibited by ciprofloxacin 2 days after phytohemagglutinin stimulation but was increased on days 3 to 6. The total incorporation of [3H]thymidine from day 1 to day 6 after phytohemagglutinin stimulation was increased by 42 to 45% at 5 to 20 micrograms of ciprofloxacin per ml. Increased [3H]thymidine incorporation was also seen when human lymphocytes were stimulated with mitogens other than phytohemagglutinin. Ciprofloxacin added at the start of the culture had a more pronounced effect on [3H]thymidine incorporation than when added later. In spite of the apparent increase in DNA synthesis, lymphocyte growth was inhibited by 20 micrograms of ciprofloxacin per ml, and cell cycle analysis showed that ciprofloxacin inhibited progression through the cell cycle. In addition, immunoglobulin secretion by human lymphocytes stimulated by pokeweed mitogen for Epstein-Barr virus was inhibited by approximately 50% at 5 micrograms of ciprofloxacin per ml. These results suggest that the 4-quinolone drugs may also affect eucaryotic cell function in vitro, but additional studies are needed to establish an in vivo relevance. PMID:3606076

  20. Overview of Development and Deployment of Codes, Standards and Regulations Affecting Energy Storage System Safety in the United States

    SciTech Connect

    Conover, David R.

    2014-08-22

    This report acquaints stakeholders and interested parties involved in the development and/or deployment of energy storage systems (ESS) with the subject of safety-related codes, standards and regulations (CSRs). It is hoped that users of this document gain a more in depth and uniform understanding of safety-related CSR development and deployment that can foster improved communications among all ESS stakeholders and the collaboration needed to realize more timely acceptance and approval of safe ESS technology through appropriate CSR.

  1. Ecology of conflict: marine food supply affects human-wildlife interactions on land

    PubMed Central

    Artelle, Kyle A.; Anderson, Sean C.; Reynolds, John D.; Cooper, Andrew B.; Paquet, Paul C.; Darimont, Chris T.

    2016-01-01

    Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960–2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km2 killed due to conflicts with humans increased by an average of 20% (6–32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1st), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID:27185189

  2. Ecology of conflict: marine food supply affects human-wildlife interactions on land.

    PubMed

    Artelle, Kyle A; Anderson, Sean C; Reynolds, John D; Cooper, Andrew B; Paquet, Paul C; Darimont, Chris T

    2016-01-01

    Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960-2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km(2) killed due to conflicts with humans increased by an average of 20% (6-32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1(st)), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID:27185189

  3. A human factors engineering paradigm for patient safety: designing to support the performance of the healthcare professional

    PubMed Central

    Karsh, B‐T; Holden, R J; Alper, S J; Or, C K L

    2006-01-01

    The goal of improving patient safety has led to a number of paradigms for directing improvement efforts. The main paradigms to date have focused on reducing injuries, reducing errors, or improving evidence based practice. In this paper a human factors engineering paradigm is proposed that focuses on designing systems to improve the performance of healthcare professionals and to reduce hazards. Both goals are necessary, but neither is sufficient to improve safety. We suggest that the road to patient and employee safety runs through the healthcare professional who delivers care. To that end, several arguments are provided to show that designing healthcare delivery systems to support healthcare professional performance and hazard reduction should yield significant patient safety benefits. The concepts of human performance and hazard reduction are explained. PMID:17142611

  4. The voice of emotion across species: how do human listeners recognize animals' affective states?

    PubMed

    Scheumann, Marina; Hasting, Anna S; Kotz, Sonja A; Zimmermann, Elke

    2014-01-01

    Voice-induced cross-taxa emotional recognition is the ability to understand the emotional state of another species based on its voice. In the past, induced affective states, experience-dependent higher cognitive processes or cross-taxa universal acoustic coding and processing mechanisms have been discussed to underlie this ability in humans. The present study sets out to distinguish the influence of familiarity and phylogeny on voice-induced cross-taxa emotional perception in humans. For the first time, two perspectives are taken into account: the self- (i.e. emotional valence induced in the listener) versus the others-perspective (i.e. correct recognition of the emotional valence of the recording context). Twenty-eight male participants listened to 192 vocalizations of four different species (human infant, dog, chimpanzee and tree shrew). Stimuli were recorded either in an agonistic (negative emotional valence) or affiliative (positive emotional valence) context. Participants rated the emotional valence of the stimuli adopting self- and others-perspective by using a 5-point version of the Self-Assessment Manikin (SAM). Familiarity was assessed based on subjective rating, objective labelling of the respective stimuli and interaction time with the respective species. Participants reliably recognized the emotional valence of human voices, whereas the results for animal voices were mixed. The correct classification of animal voices depended on the listener's familiarity with the species and the call type/recording context, whereas there was less influence of induced emotional states and phylogeny. Our results provide first evidence that explicit voice-induced cross-taxa emotional recognition in humans is shaped more by experience-dependent cognitive mechanisms than by induced affective states or cross-taxa universal acoustic coding and processing mechanisms.

  5. The Voice of Emotion across Species: How Do Human Listeners Recognize Animals' Affective States?

    PubMed Central

    Scheumann, Marina; Hasting, Anna S.; Kotz, Sonja A.; Zimmermann, Elke

    2014-01-01

    Voice-induced cross-taxa emotional recognition is the ability to understand the emotional state of another species based on its voice. In the past, induced affective states, experience-dependent higher cognitive processes or cross-taxa universal acoustic coding and processing mechanisms have been discussed to underlie this ability in humans. The present study sets out to distinguish the influence of familiarity and phylogeny on voice-induced cross-taxa emotional perception in humans. For the first time, two perspectives are taken into account: the self- (i.e. emotional valence induced in the listener) versus the others-perspective (i.e. correct recognition of the emotional valence of the recording context). Twenty-eight male participants listened to 192 vocalizations of four different species (human infant, dog, chimpanzee and tree shrew). Stimuli were recorded either in an agonistic (negative emotional valence) or affiliative (positive emotional valence) context. Participants rated the emotional valence of the stimuli adopting self- and others-perspective by using a 5-point version of the Self-Assessment Manikin (SAM). Familiarity was assessed based on subjective rating, objective labelling of the respective stimuli and interaction time with the respective species. Participants reliably recognized the emotional valence of human voices, whereas the results for animal voices were mixed. The correct classification of animal voices depended on the listener's familiarity with the species and the call type/recording context, whereas there was less influence of induced emotional states and phylogeny. Our results provide first evidence that explicit voice-induced cross-taxa emotional recognition in humans is shaped more by experience-dependent cognitive mechanisms than by induced affective states or cross-taxa universal acoustic coding and processing mechanisms. PMID:24621604

  6. Triclosan and bisphenol a affect decidualization of human endometrial stromal cells.

    PubMed

    Forte, Maurizio; Mita, Luigi; Cobellis, Luigi; Merafina, Verdiana; Specchio, Raffaella; Rossi, Sergio; Mita, Damiano Gustavo; Mosca, Lavinia; Castaldi, Maria Antonietta; De Falco, Maria; Laforgia, Vincenza; Crispi, Stefania

    2016-02-15

    In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis. Cell proliferation, cell cycle, migration and decidualization mechanisms were investigated. Treatments have been performed with both the EDCs separately or in presence and in absence of progesterone used as decidualization stimulus. Both TCL and BPA did not affect cell proliferation, but they arrested ESCs at G2/M phase of cell cycle enhancing cell migration. TCL and BPA also increased gene expression and protein levels of some decidualization markers, such as insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL), amplifying the effect of progesterone alone. All together, our data strongly suggest that TCL and BPA might alter human endometrium physiology so affecting fertility and pregnancy outcome. PMID:26604029

  7. Do different degrees of human activity affect the diet of Brazilian silverside Atherinella brasiliensis?

    PubMed

    Alves, V E N; Patrício, J; Dolbeth, M; Pessanha, A; Palma, A R T; Dantas, E W; Vendel, A L

    2016-08-01

    The aim of the present study was to test whether different degrees of human activity affect the diet of the Brazilian silverside Atherinella brasiliensis in two tropical estuaries. Fish were collected along the salinity gradient of two Brazilian estuaries, the heavily impacted Paraiba Estuary and the less impacted Mamanguape Estuary, in the dry and wet seasons. The findings confirm that A. brasiliensis has generalist feeding habits and is able to change its diet under different environmental conditions. The results indicate clear spatial (i.e. along the estuarine gradient) changes in diet composition in both estuaries, but diet was also influenced by the degree of anthropogenic disturbance. During the wet season in the nutrient enriched Paraiba Estuary, when human activity was higher, the diet of A. brasiliensis was poorer and dominated by few dietary items, reflecting the potential impoverishment of prey items in this heavily disturbed system. The specimens collected in the most affected estuary also had a greater frequency of micro-plastics and parasites in their stomachs, reflecting the greater degree of human disturbance in the estuary. The present findings suggest that the diet of A. brasiliensis could be a useful indicator of changes in the ecological quality of these and other tropical estuaries of the western Atlantic Ocean. PMID:27328827

  8. Nonsense mutations in the human. beta. -globin gene affect mRNA metabolism

    SciTech Connect

    Baserga, S.J.; Benz, E.J. Jr. )

    1988-04-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.

  9. Inference of human affective states from psychophysiological measurements extracted under ecologically valid conditions

    PubMed Central

    Betella, Alberto; Zucca, Riccardo; Cetnarski, Ryszard; Greco, Alberto; Lanatà, Antonio; Mazzei, Daniele; Tognetti, Alessandro; Arsiwalla, Xerxes D.; Omedas, Pedro; De Rossi, Danilo; Verschure, Paul F. M. J.

    2014-01-01

    Compared to standard laboratory protocols, the measurement of psychophysiological signals in real world experiments poses technical and methodological challenges due to external factors that cannot be directly controlled. To address this problem, we propose a hybrid approach based on an immersive and human accessible space called the eXperience Induction Machine (XIM), that incorporates the advantages of a laboratory within a life-like setting. The XIM integrates unobtrusive wearable sensors for the acquisition of psychophysiological signals suitable for ambulatory emotion research. In this paper, we present results from two different studies conducted to validate the XIM as a general-purpose sensing infrastructure for the study of human affective states under ecologically valid conditions. In the first investigation, we recorded and classified signals from subjects exposed to pictorial stimuli corresponding to a range of arousal levels, while they were free to walk and gesticulate. In the second study, we designed an experiment that follows the classical conditioning paradigm, a well-known procedure in the behavioral sciences, with the additional feature that participants were free to move in the physical space, as opposed to similar studies measuring physiological signals in constrained laboratory settings. Our results indicate that, by using our sensing infrastructure, it is indeed possible to infer human event-elicited affective states through measurements of psychophysiological signals under ecological conditions. PMID:25309310

  10. Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine.

    PubMed Central

    Chien, S C; Chow, A T; Rogge, M C; Williams, R R; Hendrix, C W

    1997-01-01

    This phase I, double-blind, randomized, placebo-controlled, parallel-design study was conducted to evaluate the safety and pharmacokinetics of levofloxacin in human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell counts ranging from 100 to 550 and not experiencing significant AZT intolerance were enrolled. Subjects received levofloxacin (350 mg of levofloxacin hemihydrate) or a placebo (eight subjects per treatment group) as a single oral dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with the study drug. In between these doses, AZT was administered according to the regimen used by the subject prior to entering the study up to a maximum of 500 mg/day. Plasma levofloxacin concentrations were monitored for 36 h after levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to 9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma concentration, approximately 1.0 h) and extensively distributed in the body with an apparent volume of distribution of approximately 104 liters (approximately 1.34 liters/kg). Steady-state conditions on day 10 were confirmed. Pharmacokinetic profiles of levofloxacin from single doses and multiple (three-times-daily) doses were similar, with a moderate accumulation (observed day 10-to-day 1 ratio of the maximum plasma concentration, approximately 185% versus expected 169%; for the corresponding ratio of the area under the concentration-time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus expected 169%) at steady state. Mean average steady-state peak plasma concentration, plasma levofloxacin concentration at the

  11. Cognitive and affective components of mental workload: Understanding the effects of each on human decision making behavior

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1992-01-01

    Human factors and ergonomics researchers have recognized for some time the increasing importance of understanding the role of the construct of mental workload in flight research. Current models of mental workload suggest that it is a multidimensional and complex construct, but one that has proved difficult to measure. Because of this difficulty, emphasis has usually been placed on using direct reports through subjective measures such as rating scales to assess levels of mental workload. The NASA Task Load Index (NASA/TLX, Hart and Staveland) has been shown to be a highly reliable and sensitive measure of perceived mental workload. But a problem with measures like TLX is that there is still considerable disagreement as to what it is about mental workload that these subjective measures are actually measuring. The empirical use of subjective workload measures has largely been to provide estimates of the cognitive components of the actual mental workload required for a task. However, my research suggests that these measures may, in fact have greater potential in accurately assessing the affective components of workload. That is, for example, TLX may be more likely to assess the positive and negative feelings associated with varying workload levels, which in turn may potentially influence the decision making behavior that directly bears on performance and safety issues. Pilots, for example, are often called upon to complete many complex tasks that are high in mental workload, stress, and frustration, and that have significant dynamic decision making components -- often ones that involve risk as well.

  12. Biological effects of weak blast waves and safety limits for internal organ injury in the human body.

    PubMed

    Yang, Z; Wang, Z; Tang, C; Ying, Y

    1996-03-01

    One hundred and seventeen adult sheep of both sexes, each weighing 15.2-42.4 kg, were used for this study. The purpose of this study was to investigate the relationship of the physical parameters of the waves to internal organ injury by exposing sheep to weak blast waves in TNT (trinitrotoluene) explosions, biological shock tube, and gun muzzle blasts. The results showed that the organ most sensitive to the TNT explosion was the lungs, whereas the upper respiratory tract was most sensitive to muzzle blast waves. The injury thresholds of overpressure were 29.0, 29.5, and 41.2 kPa for upper respiratory tract, lungs, and gastrointestinal tract respectively at a single exposure. Repeated exposure to 60 blasts reduced the injury threshold of the internal organs. The injury thresholds for upper respiratory tract, lungs, and gastrointestinal tract were 21.0, 18.0, and 40.4 kPa, respectively. The duration of overpressure of weak blast waves was 2.4-4.2 milliseconds, which did not significantly affect the severity of injury. The safety limits of weak blast waves to internal organ injury of human body were as follows: Ps = 37-3Ln.Tc.N/4(Tc.N < or = 1000) and Ps = 20.4(Tc.N > 1000). The results suggest that repeated exposures decrease the injury threshold of the internal organs. The safety limits proposed could protect 90% of the exposed population against internal organ injury caused by weak blast waves. PMID:8606431

  13. Intra-articular corticosteroids in the treatment of juvenile idiopathic arthritis: Safety, efficacy, and features affecting outcome. A comprehensive review of the literature

    PubMed Central

    Gotte, Alisa Carman

    2009-01-01

    Intra-articular corticosteroid injection (IACI) has been used in the treatment of inflammatory arthritis in adults for over fifty years. Over the last two decades, IACI has become an important tool in the management of juvenile idiopathic arthritis (JIA), particularly in the oligoarthritis subset of JIA. Many factors may affect the efficacy of this treatment modality, although the majority of evidence on this topic is anecdotal, nonconvincing, or conflicting. The review examines the rationale, efficacy, safety, and application of the use of IACI in the treatment of JIA, focusing on factors that affect the outcome following IACI.

  14. Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans.

    PubMed

    Márquez, Fabiola; Babio, Nancy; Bulló, Mònica; Salas-Salvadó, J

    2012-01-01

    Several studies have shown that Garcinia cambogia plays an important role in the regulation of endogenous lipid biosynthesis. This effect is specially attributed to (-)-hydroxycitric acid (HCA) inhibiting the enzyme ATP-dependent citrate lyase, which catalyzes the cleavage of citrate to oxaloacetate and acetyl-CoA. Although several studies have found that the administration of G. cambogia extracts is associated with body weight and fat loss in both experimental animals and humans, we should be cautious when interpreting the results as other randomized, placebo-controlled clinical trials have not reported the same outcomes. Furthermore, most studies in humans have been conducted on small samples and mainly in the short term. None of them have shown whether these effects persist beyond 12 weeks of intervention. Therefore, there is still little evidence to support the potential effectiveness and long-term benefits of G. cambogia extracts. With regard to toxicity and safety, it is important to note that except in rare cases, studies conducted in experimental animals have not reported increased mortality or significant toxicity. Furthermore, at the doses usually administered, no differences have been reported in terms of side effects or adverse events (those studied) in humans between individuals treated with G. cambogia and controls. PMID:22530711

  15. Safety Assessment of Two New Lactobacillus Strains as Probiotic for Human Using a Rat Model.

    PubMed

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Liang, Juan Boo; Kalavathy, Ramasamy; Sieo, Chin Chin; Ho, Yin Wan

    2016-01-01

    Two previously isolated Lactobacillus strains (L. fermentum HM3 from human milk and L. buchneri FD2 from fermented dates), intended as probiotic for human, were assessed for their safety using acute and subacute oral toxicity tests in rats. In addition, their effects on cecal microflora and harmful bacterial enzymes (β-glucuronidase and β-glucosidase) of the tested animals were also determined. The results showed that L. buchneri FD2, L. fermentum HM3, or a mixture of them were safe up to a level of 1010 CFU/kg BW/day in a 14-day or 28-day treatment period. Both strains were well tolerated and there were no observed adverse effects on growth, feed consumption, cellular blood components and vital organs of the treated animals. The Lactobacillus strains were also able to reduce harmful intestinal bacterial enzymes, and decrease pathogenic bacterial populations while increasing beneficial bacterial populations. These results suggest that the two Lactobacillus strains are safe and could be potential probiotic for human. PMID:27467068

  16. Safety Assessment of Two New Lactobacillus Strains as Probiotic for Human Using a Rat Model

    PubMed Central

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Liang, Juan Boo; Kalavathy, Ramasamy; Sieo, Chin Chin; Ho, Yin Wan

    2016-01-01

    Two previously isolated Lactobacillus strains (L. fermentum HM3 from human milk and L. buchneri FD2 from fermented dates), intended as probiotic for human, were assessed for their safety using acute and subacute oral toxicity tests in rats. In addition, their effects on cecal microflora and harmful bacterial enzymes (β-glucuronidase and β-glucosidase) of the tested animals were also determined. The results showed that L. buchneri FD2, L. fermentum HM3, or a mixture of them were safe up to a level of 1010 CFU/kg BW/day in a 14-day or 28-day treatment period. Both strains were well tolerated and there were no observed adverse effects on growth, feed consumption, cellular blood components and vital organs of the treated animals. The Lactobacillus strains were also able to reduce harmful intestinal bacterial enzymes, and decrease pathogenic bacterial populations while increasing beneficial bacterial populations. These results suggest that the two Lactobacillus strains are safe and could be potential probiotic for human. PMID:27467068

  17. Health in the hot zone - How could global warming affect humans?

    SciTech Connect

    Monastersky, R.

    1996-04-06

    A soon-to-be-released report from the World Health Organization examines the health effects of global warming, calling climate change one of the largest public health challenges for the upcoming century. The issue extends beyond tropical illness: deaths caused directly by heat, dwindling agricultural yields etc. could all affect human health. This article looks at the following health related effects and gives an overview of the scientific information available on each: temperature and mortality; tropical trouble, including vecorborne diseases and increase in susceptable populations; and waterborne problems such as cholera, harmful algal bloomes, food shortages.

  18. Does correlated color temperature affect the ability of humans to identify veins?

    PubMed

    Argyraki, Aikaterini; Clemmensen, Line Katrine Harder; Petersen, Paul Michael

    2016-01-01

    In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84-95) was developed and the effect of correlated color temperature was evaluated, in the range between 2600 and 5700 K at an illuminance of 40±9  lx on the ability of adult humans to identify veins. It is shown that the ability to identify veins can, on average, be increased up to 24% when white illumination settings that do not resemble incandescent light are applied. The illuminance reported together with the effect of white illumination settings on direct visual perception of biosamples are relevant for clinical investigations during the night. PMID:26831595

  19. Do human activities affect the picoplankton structure of the Ahe atoll lagoon (Tuamotu Archipelago, French Polynesia)?

    PubMed

    Bouvy, Marc; Dupuy, Christine; Pagano, Marc; Barani, Aude; Charpy, Loic

    2012-01-01

    The spatial variations of the picoplankton (photoautotrophic and heterotrophic microorganisms) in the Ahe atoll lagoon were studied in May and October 2008 to assess whether they were affected by human activities along the atoll. Spatial patterns were studied using 10 sampling stations chosen according to the location of the anthropogenic activities (pearl farming, harbor). Experiments were also carried out to determine whether bacterial growth, with or without predators, was limited by inorganic (N and P) substrates. The results showed that heterotrophic bacterioplankton abundance was superior to the photoautotrophic organisms, especially in May. Significant increases in bacterial abundance were observed in May after 24 h incubation with +P and +N (but not in October). All samples complied with the quality levels for fecal indicator bacteria (FIB) defined by the European Union and there was no evidence that human sewage had any impact on picoplankton over the whole atoll. PMID:22306310

  20. Do human activities affect the picoplankton structure of the Ahe atoll lagoon (Tuamotu Archipelago, French Polynesia)?

    PubMed

    Bouvy, Marc; Dupuy, Christine; Pagano, Marc; Barani, Aude; Charpy, Loic

    2012-01-01

    The spatial variations of the picoplankton (photoautotrophic and heterotrophic microorganisms) in the Ahe atoll lagoon were studied in May and October 2008 to assess whether they were affected by human activities along the atoll. Spatial patterns were studied using 10 sampling stations chosen according to the location of the anthropogenic activities (pearl farming, harbor). Experiments were also carried out to determine whether bacterial growth, with or without predators, was limited by inorganic (N and P) substrates. The results showed that heterotrophic bacterioplankton abundance was superior to the photoautotrophic organisms, especially in May. Significant increases in bacterial abundance were observed in May after 24 h incubation with +P and +N (but not in October). All samples complied with the quality levels for fecal indicator bacteria (FIB) defined by the European Union and there was no evidence that human sewage had any impact on picoplankton over the whole atoll.

  1. Fusion of nonclinical and clinical data to predict human drug safety.

    PubMed

    Johnson, Dale E

    2013-03-01

    Adverse drug reactions continue to be a major cause of morbidity in both patients receiving therapeutics and in drug R&D programs. Predicting and possibly eliminating these adverse events remains a high priority in industry, government agencies and healthcare systems. With small molecule candidates, the fusion of nonclinical and clinical data is essential in establishing an overall system that creates a true translational science approach. Several new advances are taking place that attempt to create a 'patient context' mechanism early in drug research and development and ultimately into the marketplace. This 'life-cycle' approach has as its core the development of human-oriented, nonclinical end points and the incorporation of clinical knowledge at the drug design stage. The next 5 years should witness an explosion of what the author views as druggable and safe chemical space, pharmacosafety molecular targets and the most important aspect, an understanding of unique susceptibilities in patients developing adverse drug reactions. Our current knowledge of clinical safety relies completely on pharmacovigilance data from approved and marketed drugs, with a few exceptions of drugs failing in clinical trials. Massive data repositories now and soon to be available via cloud computing should stimulate a major effort in expanding our view of clinical drug safety and its incorporation into early drug research and development.

  2. Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure

    NASA Astrophysics Data System (ADS)

    Laakso, Ilkka; Hirata, Akimasa

    2011-12-01

    Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters—some of which may be subject to considerable uncertainty—that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg-1.

  3. Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles

    PubMed Central

    Waterland, Robert A.; Kellermayer, Richard; Laritsky, Eleonora; Rayco-Solon, Pura; Harris, R. Alan; Travisano, Michael; Zhang, Wenjuan; Torskaya, Maria S.; Zhang, Jiexin; Shen, Lanlan; Manary, Mark J.; Prentice, Andrew M.

    2010-01-01

    Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease. PMID:21203497

  4. Factors affecting circulating levels of peptide YY in humans: a comprehensive review.

    PubMed

    Cooper, Jamie A

    2014-06-01

    As obesity continues to be a global epidemic, research into the mechanisms of hunger and satiety and how those signals act to regulate energy homeostasis persists. Peptide YY (PYY) is an acute satiety signal released upon nutrient ingestion and has been shown to decrease food intake when administered exogenously. More recently, investigators have studied how different factors influence PYY release and circulating levels in humans. Some of these factors include exercise, macronutrient composition of the diet, body-weight status, adiposity levels, sex, race and ageing. The present article provides a succinct and comprehensive review of the recent literature published on the different factors that influence PYY release and circulating levels in humans. Where human data are insufficient, evidence in animal or cell models is summarised. Additionally, the present review explores the recent findings on PYY responses to different dietary fatty acids and how this new line of research will make an impact on future studies on PYY. Human demographics, such as sex and age, do not appear to influence PYY levels. Conversely, adiposity or BMI, race and acute exercise all influence circulating PYY levels. Both dietary fat and protein strongly stimulate PYY release. Furthermore, MUFA appear to result in a smaller PYY response compared with SFA and PUFA. PYY levels appear to be affected by acute exercise, macronutrient composition, adiposity, race and the composition of fatty acids from dietary fat.

  5. In silico assessment of drug safety in human heart applied to late sodium current blockers

    PubMed Central

    Trenor, Beatriz; Gomis-Tena, Julio; Cardona, Karen; Romero, Lucia; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R; Saiz, Javier

    2013-01-01

    Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (INaL) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K+ current (IKr). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of IKr/INaL ratio of steady-state block of drug candidates on “torsadogenic” biomarkers. The O’Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of INaL and IKr were evaluated. “Safety plots” were developed to illustrate the value of the specific biomarker for selected combinations of IC50s for IKr and INaL of potential drugs. The reference biomarkers at baseline changed depending on the “drug” specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of INaL) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle. PMID:23696033

  6. Human factors and safety issues associated with actinide retrieval from spent light water reactor fuel assemblies

    SciTech Connect

    Spelt, P.F.

    1992-01-01

    A major problem in environmental restoration and waste management is the disposition of used fuel assemblies from the many light water reactors in the United States, which present a radiation hazard to those whose job is to dispose of them, with a similar threat to the general environment associated with long-term storage in fuel repositories around the country. Actinides resident in the fuel pins as a result of their use in reactor cores constitute a significant component of this hazard. Recently, the Department of Energy has initiated an Actinide Recycle Program to study the feasibility of using pyrochemical (molten salt) processes to recover actinides from the spent fuel assemblies of commercial reactors. This project concerns the application of robotics technology to the operation and maintenance functions of a plant whose objective is to recover actinides from spent fuel assemblies, and to dispose of the resulting hardware and chemical components from this process. Such a procedure involves a number of safety and human factors issues. The purpose of the project is to explore the use of robotics and artificial intelligence to facilitate accomplishment of the program goals while maintaining the safety of the humans doing the work and the integrity of the environment. This project will result in a graphic simulation on a Silicon Graphics workstation as a proof of principle demonstration of the feasibility of using robotics along with an intelligent operator interface. A major component of the operator-system interface is a hybrid artificial intelligence system developed at Oak Ridge National Laboratory, which combines artificial neural networks and an expert system into a hybrid, self-improving computer-based system interface. 10 refs.

  7. Human factors and safety issues associated with actinide retrieval from spent light water reactor fuel assemblies

    SciTech Connect

    Spelt, P.F.

    1992-08-01

    A major problem in environmental restoration and waste management is the disposition of used fuel assemblies from the many light water reactors in the United States, which present a radiation hazard to those whose job is to dispose of them, with a similar threat to the general environment associated with long-term storage in fuel repositories around the country. Actinides resident in the fuel pins as a result of their use in reactor cores constitute a significant component of this hazard. Recently, the Department of Energy has initiated an Actinide Recycle Program to study the feasibility of using pyrochemical (molten salt) processes to recover actinides from the spent fuel assemblies of commercial reactors. This project concerns the application of robotics technology to the operation and maintenance functions of a plant whose objective is to recover actinides from spent fuel assemblies, and to dispose of the resulting hardware and chemical components from this process. Such a procedure involves a number of safety and human factors issues. The purpose of the project is to explore the use of robotics and artificial intelligence to facilitate accomplishment of the program goals while maintaining the safety of the humans doing the work and the integrity of the environment. This project will result in a graphic simulation on a Silicon Graphics workstation as a proof of principle demonstration of the feasibility of using robotics along with an intelligent operator interface. A major component of the operator-system interface is a hybrid artificial intelligence system developed at Oak Ridge National Laboratory, which combines artificial neural networks and an expert system into a hybrid, self-improving computer-based system interface. 10 refs.

  8. Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.

    PubMed Central

    Stewart, D. J.; Molepo, J. M.; Green, R. M.; Montpetit, V. A.; Hugenholtz, H.; Lamothe, A.; Mikhael, N. Z.; Redmond, M. D.; Gadia, M.; Goel, R.

    1995-01-01

    We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours. PMID:7880744

  9. Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive.

    PubMed

    Odenthal-Hesse, Linda; Berg, Ingrid L; Veselis, Amelia; Jeffreys, Alec J; May, Celia A

    2014-02-01

    Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes. PMID:24516398

  10. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease.

    PubMed

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L; Brull, Astrid; Andreu, Antoni L; Vissing, John

    2016-05-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray, variations in fiber size, vacuoles, and some internal nuclei associated with cytosolic glycogen accumulation and ongoing regeneration; structural damage was seen only in a minority of human patients. Neither liver nor brain isoforms of glycogen phosphorylase were upregulated in muscles, thus providing no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus, despite differences, the mouse model of McArdle disease shares fundamental physiological and clinical features with the human disease and could be used for studies of pathogenesis and development of therapies. PMID:27030740

  11. Relevance of UV filter/sunscreen product photostability to human safety.

    PubMed

    Nash, J Frank; Tanner, Paul R

    2014-01-01

    Photostability or photo-instability of sunscreen products is most often discussed in undesirable terms with respect to human safety. The health risks, specifically associated with sunscreens, photostable or photo-unstable, include phototoxic/photoirritation or photoallergic responses and, longer-term, an increased risk of skin cancers or photoageing. The aims of this paper are to define photostability/photo-instability and objectively assess the acute and chronic toxicological consequences from the human exposure to UV filter/sunscreens and any probable photo-degradation products. The reported prevalence of photoirritation and photoallergic responses to sunscreens is rare compared with adverse events, for example, skin irritation or sensitization, produced by cosmetics or topically applied drugs and do not directly implicate potential photo-degradation products of UV filters. Moreover, for at least one photo-unstable combination, octyl methoxycinnamate and avobenzone, the long-term benefits to humans, i.e., reduction in skin cancers, seem to outweigh any potential adverse consequences attributed to photo-degradation. Sunscreen products are formulated to achieve maximum efficacy which, by necessity and design, incorporate measures to support and promote photostability since all organic UV filters have the potential to photo-degrade. Current performance measures, in vivo SPF and in vitro UVA, conducted under standardized conditions, in part account for photostability. The concerns expressed when considering human exposure to potential photo-unstable UV filters or sunscreen products may not manifest as health risks under conditions of use. Still, improvement in sunscreen product photostability continues to be a key strategic objective for manufacturers.

  12. Human erythrocytes and neuroblastoma cells are in vitro affected by sodium orthovanadate.

    PubMed

    Suwalsky, M; Fierro, P; Villena, F; Aguilar, L F; Sotomayor, C P; Jemiola-Rzeminska, M; Strzalka, K; Gul-Hinc, S; Ronowska, A; Szutowicz, A

    2012-09-01

    Research on biological influence of vanadium has gained major importance because it exerts potent toxic, mutagenic, and genotoxic effects on a wide variety of biological systems. However, hematological toxicity is one of the less studied effects. The lack of information on this issue prompted us to study the structural effects induced on the human erythrocyte membrane by vanadium (V). Sodium orthovanadate was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence in order that orthovanadate interacted with red cell membranes as follows: a) in scanning electron microscopy (SEM) studies it was observed that morphological changes on human erythrocytes were induced; b) fluorescence spectroscopy experiments in isolated unsealed human erythrocyte membranes (IUM) showed that an increase in the molecular dynamics and/or water content at the shallow depth of the lipids glycerol backbone at concentrations as low as 50μM was produced; c) X-ray diffraction studies showed that orthovanadate 0.25-1mM range induced increasing structural perturbation to DMPE; d) somewhat similar effects were observed by differential scanning calorimetry (DSC) with the exception of the fact that DMPC pretransition was shown to be affected; and e) fluorescence spectroscopy experiments performed in DMPC large unilamellar vesicles (LUV) showed that at very low concentrations induced changes in DPH fluorescence anisotropy at 18°C. Additional experiments were performed in mice cholinergic neuroblastoma SN56 cells; a statistically significant decrease of cell viability was observed on orthovanadate in low or moderate concentrations. PMID:22546530

  13. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    PubMed

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. PMID:27103578

  14. Latent Variables Affecting Behavioral Response to the Human Intruder Test in Infant Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Gottlieb, Daniel H.; Capitanio, John P.

    2012-01-01

    The human intruder test is a testing paradigm designed to measure rhesus macaques’ behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over twenty years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3–4 month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001–2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: “Activity,” “Emotionality,” “Aggression,” and “Displacement.” Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially-reared animals had the lowest Activity score (P < 0.001), indoor mother-reared animals had the highest Displacement score (P < 0.001), and nursery-reared animals had the highest Emotionality (P < 0.001) and lowest Aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal’s rearing history. PMID:23229557

  15. Identification of Climatic Factors Affecting the Epidemiology of Human West Nile Virus Infections in Northern Greece.

    PubMed

    Stilianakis, Nikolaos I; Syrris, Vasileios; Petroliagkis, Thomas; Pärt, Peeter; Gewehr, Sandra; Kalaitzopoulou, Stella; Mourelatos, Spiros; Baka, Agoritsa; Pervanidou, Danai; Vontas, John; Hadjichristodoulou, Christos

    2016-01-01

    Climate can affect the geographic and seasonal patterns of vector-borne disease incidence such as West Nile Virus (WNV) infections. We explore the association between climatic factors and the occurrence of West Nile fever (WNF) or West Nile neuro-invasive disease (WNND) in humans in Northern Greece over the years 2010-2014. Time series over a period of 30 years (1979-2008) of climatic data of air temperature, relative humidity, soil temperature, volumetric soil water content, wind speed, and precipitation representing average climate were obtained utilising the ECMWF's (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-Interim) system allowing for a homogeneous set of data in time and space. We analysed data of reported human cases of WNF/WNND and Culex mosquitoes in Northern Greece. Quantitative assessment resulted in identifying associations between the above climatic variables and reported human cases of WNF/WNND. A substantial fraction of the cases was linked to the upper percentiles of the distribution of air and soil temperature for the period 1979-2008 and the lower percentiles of relative humidity and soil water content. A statistically relevant relationship between the mean weekly value climatic anomalies of wind speed (negative association), relative humidity (negative association) and air temperature (positive association) over 30 years, and reported human cases of WNF/WNND during the period 2010-2014 could be shown. A negative association between the presence of WNV infected Culex mosquitoes and wind speed could be identified. The statistically significant associations could also be confirmed for the week the WNF/WNND human cases appear and when a time lag of up to three weeks was considered. Similar statistically significant associations were identified with the weekly anomalies of the maximum and minimum values of the above climatic factors. Utilising the ERA-Interim re-analysis methodology it could be shown that besides air

  16. Identification of Climatic Factors Affecting the Epidemiology of Human West Nile Virus Infections in Northern Greece.

    PubMed

    Stilianakis, Nikolaos I; Syrris, Vasileios; Petroliagkis, Thomas; Pärt, Peeter; Gewehr, Sandra; Kalaitzopoulou, Stella; Mourelatos, Spiros; Baka, Agoritsa; Pervanidou, Danai; Vontas, John; Hadjichristodoulou, Christos

    2016-01-01

    Climate can affect the geographic and seasonal patterns of vector-borne disease incidence such as West Nile Virus (WNV) infections. We explore the association between climatic factors and the occurrence of West Nile fever (WNF) or West Nile neuro-invasive disease (WNND) in humans in Northern Greece over the years 2010-2014. Time series over a period of 30 years (1979-2008) of climatic data of air temperature, relative humidity, soil temperature, volumetric soil water content, wind speed, and precipitation representing average climate were obtained utilising the ECMWF's (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-Interim) system allowing for a homogeneous set of data in time and space. We analysed data of reported human cases of WNF/WNND and Culex mosquitoes in Northern Greece. Quantitative assessment resulted in identifying associations between the above climatic variables and reported human cases of WNF/WNND. A substantial fraction of the cases was linked to the upper percentiles of the distribution of air and soil temperature for the period 1979-2008 and the lower percentiles of relative humidity and soil water content. A statistically relevant relationship between the mean weekly value climatic anomalies of wind speed (negative association), relative humidity (negative association) and air temperature (positive association) over 30 years, and reported human cases of WNF/WNND during the period 2010-2014 could be shown. A negative association between the presence of WNV infected Culex mosquitoes and wind speed could be identified. The statistically significant associations could also be confirmed for the week the WNF/WNND human cases appear and when a time lag of up to three weeks was considered. Similar statistically significant associations were identified with the weekly anomalies of the maximum and minimum values of the above climatic factors. Utilising the ERA-Interim re-analysis methodology it could be shown that besides air

  17. Identification of Climatic Factors Affecting the Epidemiology of Human West Nile Virus Infections in Northern Greece

    PubMed Central

    Stilianakis, Nikolaos I.; Syrris, Vasileios; Petroliagkis, Thomas; Pärt, Peeter; Gewehr, Sandra; Kalaitzopoulou, Stella; Mourelatos, Spiros; Baka, Agoritsa; Pervanidou, Danai; Vontas, John; Hadjichristodoulou, Christos

    2016-01-01

    Climate can affect the geographic and seasonal patterns of vector-borne disease incidence such as West Nile Virus (WNV) infections. We explore the association between climatic factors and the occurrence of West Nile fever (WNF) or West Nile neuro-invasive disease (WNND) in humans in Northern Greece over the years 2010–2014. Time series over a period of 30 years (1979–2008) of climatic data of air temperature, relative humidity, soil temperature, volumetric soil water content, wind speed, and precipitation representing average climate were obtained utilising the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-Interim) system allowing for a homogeneous set of data in time and space. We analysed data of reported human cases of WNF/WNND and Culex mosquitoes in Northern Greece. Quantitative assessment resulted in identifying associations between the above climatic variables and reported human cases of WNF/WNND. A substantial fraction of the cases was linked to the upper percentiles of the distribution of air and soil temperature for the period 1979–2008 and the lower percentiles of relative humidity and soil water content. A statistically relevant relationship between the mean weekly value climatic anomalies of wind speed (negative association), relative humidity (negative association) and air temperature (positive association) over 30 years, and reported human cases of WNF/WNND during the period 2010–2014 could be shown. A negative association between the presence of WNV infected Culex mosquitoes and wind speed could be identified. The statistically significant associations could also be confirmed for the week the WNF/WNND human cases appear and when a time lag of up to three weeks was considered. Similar statistically significant associations were identified with the weekly anomalies of the maximum and minimum values of the above climatic factors. Utilising the ERA-Interim re-analysis methodology it could be shown that besides

  18. The impact of pre- and/or probiotics on human colonic metabolism: does it affect human health?

    PubMed

    De Preter, Vicky; Hamer, Henrike M; Windey, Karen; Verbeke, Kristin

    2011-01-01

    Since many years, the role of the colonic microbiota in maintaining the host's overall health and well-being has been recognized. Dietary modulation of the microbiota composition and activity has been achieved by the use of pre-, pro- and synbiotics. In this review, we will summarize the available evidence on the modification of bacterial metabolism by dietary intervention with pre-, pro- and synbiotics. Enhanced production of SCFA as a marker of increased saccharolytic fermentation is well documented in animal and in vitro studies. Decreased production of potentially toxic protein fermentation metabolites, such as sulfides, phenolic and indolic compounds, has been less frequently demonstrated. Besides, pre-, pro- and synbiotics also affect other metabolic pathways such as the deconjugation of secondary bile acids, bacterial enzyme activities and mineral absorption. Data from human studies are less conclusive. The emergence of new analytical techniques such as metabolite profiling has revealed new pathways affected by dietary intervention. However, an important challenge for current and future research is to relate changes in bacterial metabolism to concrete health benefits. Potential targets and expected benefits have been identified: reduced risk for the metabolic syndrome and prevention of colorectal cancer. PMID:21207512

  19. 4-Methylthiobutyl isothiocyanate (Erucin) from rocket plant dichotomously affects the activity of human immunocompetent cells.

    PubMed

    Gründemann, Carsten; Garcia-Käufer, Manuel; Lamy, Evelyn; Hanschen, Franziska S; Huber, Roman

    2015-03-15

    Isothiocyanates (ITC) from the Brassicaceae plant family are regarded as promising for prevention and treatment of cancer. However, experimental settings consider their therapeutic action without taking into account the risk of unwanted effects on healthy tissues. In the present study we investigated the effects of Eruca sativa seed extract containing MTBITC (Erucin) and pure Erucin from rocket plant on healthy cells of the human immune system in vitro. Hereby, high doses of the plant extract as well as of Erucin inhibited cell viability of human lymphocytes via induction of apoptosis to comparable amounts. Non-toxic low concentrations of the plant extract and pure Erucin altered the expression of the interleukin (IL)-2 receptor but did not affect further T cell activation, proliferation and the release of the effector molecules interferon (IFN)-gamma and IL-2 of T-lymphocytes. However, the activity of NK-cells was significantly reduced by non-toxic concentrations of the plant extract and pure Erucin. These results indicate that the plant extract and pure Erucin interfere with the function of human T lymphocytes and decreases the activity of NK-cells in comparable concentrations. Long-term clinical studies with ITC-enriched plant extracts from Brassicaceae should take this into account.

  20. Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture

    PubMed Central

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Miraldi, Fabio; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation. Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells. Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production. Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures. PMID:27340620

  1. Human cells and cell membrane molecular models are affected in vitro by chlorpromazine.

    PubMed

    Suwalsky, Mario; Villena, Fernando; Sotomayor, Carlos P; Bolognin, Silvia; Zatta, Paolo

    2008-06-01

    This study presents evidence that chlorpromazine (CPZ) affects human cells and cell membrane molecular models. Human SH-SY5Y neuroblastoma cells incubated with 0.1 mM CPZ suffered a decrease of cell viability. On the other hand, phase contrast microscopy observations of human erythrocytes indicated that they underwent a morphological alteration as 1 microM CPZ changed their discoid normal shape to stomatocytes, and to hemolysis with 1 mM CPZ. X-ray diffraction experiments performed on dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of the major phospholipids present in the outer and inner sides of the erythrocyte membrane, respectively showed that CPZ disordered the polar head and acyl chain regions of both DMPC and DMPE, where these interactions were stronger with DMPC bilayers. Fluorescence spectroscopy on DMPC LUV at 18 degrees C confirmed these results. In fact, the assays showed that CPZ induced a significant reduction of their generalized polarization (GP) and anisotropy (r) values, indicative of enhanced disorder at the polar head and acyl chain regions of the DMPC lipid bilayer. PMID:18372093

  2. Fya/Fyb antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria

    PubMed Central

    King, Christopher L.; Adams, John H.; Xianli, Jia; Grimberg, Brian T.; McHenry, Amy M.; Greenberg, Lior J.; Siddiqui, Asim; Howes, Rosalind E.; da Silva-Nunes, Monica; Ferreira, Marcelo U.; Zimmerman, Peter A.

    2011-01-01

    Plasmodium vivax (Pv) is a major cause of human malaria and is increasing in public health importance compared with falciparum malaria. Pv is unique among human malarias in that invasion of erythrocytes is almost solely dependent on the red cell's surface receptor, known as the Duffy blood-group antigen (Fy). Fy is an important minor blood-group antigen that has two immunologically distinct alleles, referred to as Fya or Fyb, resulting from a single-point mutation. This mutation occurs within the binding domain of the parasite's red cell invasion ligand. Whether this polymorphism affects susceptibility to clinical vivax malaria is unknown. Here we show that Fya, compared with Fyb, significantly diminishes binding of Pv Duffy binding protein (PvDBP) at the erythrocyte surface, and is associated with a reduced risk of clinical Pv in humans. Erythrocytes expressing Fya had 41–50% lower binding compared with Fyb cells and showed an increased ability of naturally occurring or artificially induced antibodies to block binding of PvDBP to their surface. Individuals with the Fya+b− phenotype demonstrated a 30–80% reduced risk of clinical vivax, but not falciparum malaria in a prospective cohort study in the Brazilian Amazon. The Fya+b− phenotype, predominant in Southeast Asian and many American populations, would confer a selective advantage against vivax malaria. Our results also suggest that efficacy of a PvDBP-based vaccine may differ among populations with different Fy phenotypes. PMID:22123959

  3. The cross-mammalian neurophenomenology of primal emotional affects: From animal feelings to human therapeutics.

    PubMed

    Panksepp, Jaak

    2016-06-01

    The neural correlates of human emotions are easy to harvest. In contrast, the neural constitution of emotional feelings in humans has resisted systematic scientific analysis. This review summarizes how preclinical affective neuroscience initiatives are making progress in decoding the neural nature of such feelings in animal brains. This has been achieved by studying the rewarding and punishing effects of deep brain stimulation (DBS) of subcortical emotional networks (labeled SEEING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY systems) that evoke distinct emotion action patterns, as well as rewarding and punishing effects in animals. The implications of this knowledge for development of new psychiatric interventions, especially depression, are discussed. Three new antidepressive therapeutics arising from this work are briefly noted: 1) DBS of the medial forebrain bundle (MFB) in humans, 2) reduction of psychological pain that may arise from excessive PANIC arousal, and 3) facilitation of social joy through the study of social play in rats The overall argument is that we may more readily develop new psychiatric interventions through preclinical models if we take animal emotional feelings seriously, as opposed to just behavioral changes, as targets for development of new treatments. PMID:26876723

  4. Assuring safety without animal testing: the case for the human testis in vitro.

    PubMed

    Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

    2013-08-01

    From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable.

  5. Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex?

    PubMed

    Vennewald, Nadja; Winter, Bernward; Limburg, Karina; Diemer, Julia; Notzon, Swantje; Fohrbeck, Inga; Arolt, Volker; Domschke, Katharina; Pauli, Paul; Zwanzger, Peter

    2016-10-01

    Repetitive transcranial magnetic stimulation (rTMS) enables the local and non-invasive modulation of cortical activity and has proved to achieve antidepressant effects. To a lesser extent, rTMS is investigated as a treatment option for anxiety disorders. As the prefrontal cortex and the amygdala represent key components of human emotion regulation, we investigated how prefrontally applied rTMS affects the responsiveness of the subcortical amygdala during a fear-relevant study paradigm to examine potential cortico-limbic effects. Sham-controlled, randomised inhibitory rTMS (continuous theta burst stimulation, TBS) was applied to 102 healthy subjects (female = 54) over the right dorsolateral prefrontal cortex. Subsequently, the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) acoustic startle response was investigated. Subjective anxiety ratings (anxiety sensitivity, trait and state anxiety) were considered. Picture category affected the startle magnitude as expected for both TBS intervention groups (highest startle response for unpleasant, lowest for pleasant pictures). However, no modulatory effects of TBS on startle potentiation were discerned. No significant interaction effects of TBS intervention, subjective anxiety ratings, and gender were identified. Interestingly, startle habituation was influenced by TBS intervention on a trend-level, with verum TBS leading to an accelerated habituation. We found no evidence for the hypothesis that prefrontal inhibitory TBS affects the responsiveness of the amygdala during the presentation of emotionally relevant stimuli in healthy subjects. Instead, we found accelerated habituation under verum TBS on a statistical trend-level. Hence, some preliminary hints for modulatory effects of inhibitory TBS on basic learning mechanisms could be found.

  6. The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions.

    PubMed

    Betella, Alberto; Verschure, Paul F M J

    2016-01-01

    Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID:26849361

  7. The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions

    PubMed Central

    Betella, Alberto; Verschure, Paul F. M. J.

    2016-01-01

    Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID:26849361

  8. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    PubMed

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  9. Exposure to Phthalates Affects Calcium Handling and Intercellular Connectivity of Human Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Posnack, Nikki Gillum; Idrees, Rabia; Ding, Hao; Jaimes III, Rafael; Stybayeva, Gulnaz; Karabekian, Zaruhi; Laflamme, Michael A.; Sarvazyan, Narine

    2015-01-01

    Background The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes. Methods and Results The effect of DEHP on calcium handling was examined using monolayers of gCAMP3 human embryonic stem cell-derived cardiomyocytes, which contain an endogenous calcium sensor. Cardiomyocytes were exposed to DEHP (5 – 50 μg/mL), and calcium transients were recorded using a Zeiss confocal imaging system. DEHP exposure (24 – 72 hr) had a negative chronotropic and inotropic effect on cardiomyocytes, increased the minimum threshold voltage required for external pacing, and modified connexin-43 expression. Application of Wy-14,643 (100 μM), an agonist for the peroxisome proliferator-activated receptor alpha, did not replicate DEHP’s effects on calcium transient morphology or spontaneous beating rate. Conclusions Phthalates can affect the normal physiology of human cardiomyocytes, including DEHP elicited perturbations in cardiac calcium handling and intercellular connectivity. Our findings call for additional studies to clarify the extent by which phthalate exposure can alter cardiac function, particularly in vulnerable patient populations who are at risk for high phthalate exposure. PMID:25799571

  10. GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant human Growth Hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, t...

  11. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    SciTech Connect

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  12. Copper, lead and zinc concentrations of human breast milk as affected by maternal dietary practices

    SciTech Connect

    Umoren, J.; Kies, C.

    1986-03-01

    Maternal dietary practices have been found to affect the concentrations of some nutrients in human breast milk. Lead toxicity is a concern in young children. Lead, copper and zinc are thought to compete for intestinal absorption sites. The objective of the current project was to compare copper, lead and zinc contents of breast milk from practicing lacto-vegetarian and omnivore, lactating women at approximately four months post-partum. Analyses were done by atomic absorption spectrophotometry using a carbon rod attachment. Copper concentrations were higher in milk samples from lacto-ovo-vegetarians. Milk samples from the omnivores had the highest lead and zinc concentrations. Lead and copper concentrations in milk were negatively correlated. The higher zinc concentrations in the milk of the omnivore women may have been related to better utilization of zinc from meat than from plant food sources.

  13. Factors Affecting the Absorption, Metabolism, and Excretion of Cocoa Flavanols in Humans.

    PubMed

    Cifuentes-Gomez, Tania; Rodriguez-Mateos, Ana; Gonzalez-Salvador, Isidro; Alañon, María Elena; Spencer, Jeremy P E

    2015-09-01

    Cocoa is rich in a subclass of flavonoids known as flavanols, the cardiovascular health benefits of which have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich food consumption is likely to mediate the physiological effects on the vascular system, and these levels are influenced by numerous factors, including food matrix, processing, intake, age, gender, or genetic polymorphisms, among others. This review will focus on our current understanding of factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. Second, it will identify gaps in these contributing factors that need to be addressed to conclusively translate our collective knowledge into the context of public health, dietary guidelines, and evidence-based dietary recommendations.

  14. Rewards, aversions and affect in adolescence: Emerging convergences across laboratory animal and human data

    PubMed Central

    Spear, Linda Patia

    2011-01-01

    The adolescent transition is associated with increases in reward- and sensation-seeking, peer-directed social interactions, and risk-taking, with exploratory use of alcohol and other drugs often beginning at this time. These age-related behaviors may have biological roots embedded in the evolutionary past, with similar adolescent-typical characteristics evident across a variety of mammalian species. Drawing across human behavioral and fMRI data and studies conducting in laboratory animals, this review examines processing of rewards, aversions, and affect in adolescence. Evidence for both hyper- and hypo-reactivity during adolescence in the processing of rewards is reviewed, along with possible contributors to these differences. Indications of sometimes heightened reward reactivity during adolescence are contrasted with frequent attenuations in adolescent sensitivity to aversive stimuli. At the same time, adolescents appear particularly prone to becoming emotionally aroused, especially in social contexts. Emerging evidence hints that exaggerated adolescent reactivity in reward and affective systems may be promoted in part by unusual strong cross-reactivity between these systems during adolescence. Such age-related propensities may promote adolescent risk taking, especially in social and exciting contexts, and contribute to adolescent-typical propensities to attach greater benefit and less cost to risky behaviors such as alcohol and drug use than individuals at other ages. PMID:21918675

  15. Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

    PubMed

    Sami, Musa Basser; Rabiner, Eugenii A; Bhattacharyya, Sagnik

    2015-08-01

    A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated at the neurochemical level is unclear. While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality. One would thus expect cannabis use to be associated with dopamine signaling alterations. This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man. We aimed to review all studies conducted in man, with any reported neurochemical outcomes related to the dopamine system after cannabis, cannabinoid or endocannabinoid administration or use. We identified 25 studies reporting outcomes on over 568 participants, of which 244 participants belonged to the cannabis/cannabinoid exposure group. In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. However some work has suggested that acute cannabis exposure increases dopamine release in striatal and pre-frontal areas in those genetically predisposed for, or at clinical high risk of psychosis. Furthermore, recent studies are suggesting that chronic cannabis use blunts dopamine synthesis and dopamine release capacity. Further well-designed studies are required to definitively delineate the effects of cannabis use on the dopaminergic system in man.

  16. Human resources management and firm performance: The differential role of managerial affective and continuance commitment.

    PubMed

    Gong, Yaping; Law, Kenneth S; Chang, Song; Xin, Katherine R

    2009-01-01

    In this study, the authors developed a dual-concern (i.e., maintenance and performance) model of human resources (HR) management. The authors identified commonly examined HR practices that apply to the middle manager level and classified them into the maintenance- and performance-oriented HR subsystems. The authors found support for the 2-factor model on the basis of responses from 2,148 managers from 463 firms operating in China. Regression results indicate that the performance-oriented HR subsystems had a positive relationship with firm performance and that the relationship was mediated by middle managers' affective commitment to the firm. The maintenance-oriented HR subsystems had a positive relationship with middle managers' continuance commitment but not with their affective commitment and firm performance. This study contributes to the understanding of how HR practices relate to firm performance and offers an improved test of the argument that valuable and firm-specific HR provide a source of competitive advantage. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  17. Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts

    SciTech Connect

    Dai, Jiawen; Itahana, Koji; Baskar, Rajamanickam

    2015-02-27

    Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G{sub 1}/S or G{sub 2}/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G{sub 0}, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its

  18. Human behavior state profile mapping based on recalibrated speech affective space model.

    PubMed

    Kamaruddin, N; Wahab, A

    2012-01-01

    People typically associate health with only physical health. However, health is also interconnected to mental and emotional health. People who are emotionally healthy are in control of their behaviors and experience better quality of life. Hence, understanding human behavior is very important in ensuring the complete understanding of one's holistic health. In this paper, we attempt to map human behavior state (HBS) profiles onto recalibrated speech affective space model (rSASM). Such an approach is derived from hypotheses that: 1) Behavior is influenced by emotion, 2) Emotion can be quantified through speech, 3) Emotion is dynamic and changes over time and 4) the emotion conveyance is conditioned by culture. Empirical results illustrated that the proposed approach can complement other types of behavior analysis in such a way that it offers more explanatory components from the perspective of emotion primitives (valence and arousal). Four different driving HBS; namely: distracted, laughing, sleepy and normal are profiled onto the rSASM to visualize the correlation between HBS and emotion. This approach can be incorporated in the future behavior analysis to envisage better performance.

  19. Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

    SciTech Connect

    Borella, P.; Giardino, A. )

    1991-08-01

    The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 {mu}g/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb were measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and the authors support the hypothesis that differences in the metallothionein (MT) inducibility could play a role.

  20. 50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

    NASA Astrophysics Data System (ADS)

    Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

    2004-12-01

    In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

  1. The absence of numbers to express the amount may affect delay discounting with humans.

    PubMed

    Reyes-Huerta, Hugo E; Dos Santos, Cristiano V

    2016-09-01

    Human delay discounting is usually studied with experimental protocols that use symbols to express delay and amount. In order to further understand discounting, we evaluated whether the absence of numbers to represent reward amounts affects discount rate in general, and whether the magnitude effect is generalized to nonsymbolic situations in particular. In Experiment 1, human participants were exposed to a delay-discounting task in which rewards were presented using dots to represent monetary rewards (nonsymbolic); under this condition the magnitude effect did not occur. Nevertheless, the magnitude effect was observed when equivalent reward amounts were presented using numbers (symbolic). Moreover, in estimation tasks, magnitude increments produced underestimation of large amounts. In Experiment 2, participants were exposed only to the nonsymbolic discounting task and were required to estimate reward amounts in each trial. Consistent with Experiment 1, the absence of numbers representing reward amounts produced similar discount rates of small and large rewards. These results suggest that value of nonsymbolic rewards is a nonlinear function of amount and that value attribution depends on perceived difference between the immediate and the delayed nonsymbolic rewards.

  2. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  3. A recent evolutionary change affects a regulatory element in the human FOXP2 gene.

    PubMed

    Maricic, Tomislav; Günther, Viola; Georgiev, Oleg; Gehre, Sabine; Curlin, Marija; Schreiweis, Christiane; Naumann, Ronald; Burbano, Hernán A; Meyer, Matthias; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Gajovic, Srecko; Kelso, Janet; Enard, Wolfgang; Schaffner, Walter; Pääbo, Svante

    2013-04-01

    The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.

  4. Ceramide metabolism is affected by obesity and diabetes in human adipose tissue.

    PubMed

    Błachnio-Zabielska, A U; Pułka, M; Baranowski, M; Nikołajuk, A; Zabielski, P; Górska, M; Górski, J

    2012-02-01

    Ceramide is involved in development of insulin resistance. However, there are no data on ceramide metabolism in human adipose tissue. The aim of our study was to examine sphingolipid metabolism in fat tissue from obese nondiabetic (n = 11), obese diabetic (n = 11), and lean nondiabetic (n = 8) subjects. The content of ceramide (Cer), dihydroceramide (dhCer), sphingosine (SPH), sphinganine (SPA), sphingosine-1-phosphate (S1P; pmol/mg of protein), the expression (mRNA) and activity of key enzymes responsible for Cer metabolism: serine palmitoyltransferase (SPT), neutral and acidic sphingomyelinase (nSMase and aSMase, respectively), and neutral and acidic ceramidase (nCDase and aCDase, respectively) were examined in human adipose tissue. The contents of SPA and Cer were significantly lower whereas the content of dhCer was higher in both obese groups than the respective values in the lean subjects. The expression of examined enzymes was elevated in both obese groups. The SPT and CDases activity increased whereas aSMase activity deceased in both obese groups. We have found correlation between adipose tissue Cer content and plasma adiponectin concentration (r = 0.69, P < 0.001) and negative correlation between total Cer content and HOMA-IR index (homeostasis model of insulin resistance) (r = -0.67, P < 0.001). We have found that both obesity and diabetes affected pathways of sphingolipid metabolism in the adipose tissue.

  5. Interacting Physical and Biological Processes Affecting Nutrient Transport Through Human Dominated Landscapes

    NASA Astrophysics Data System (ADS)

    Finlay, J. C.

    2015-12-01

    Human activities increasingly dominate biogeochemical cycles of limiting nutrients on Earth. Urban and agricultural landscapes represent the largest sources of excess nutrients that drive water quality degradation. The physical structure of both urban and agricultural watersheds has been extensively modified, and these changes have large impacts on water and nutrient transport. Despite strong physical controls over nutrient transport in human dominated landscapes, biological processes play important roles in determining the fates of both nitrogen and phosphorus. This talk uses examples from research in urban and agricultural watersheds in the Midwestern USA to illustrate interactions of physical and biological controls over nutrient cycles that have shifted nitrogen (N) and phosphorus (P) sources and cycling in unexpected ways in response to management changes. In urban watersheds, efforts to improve water quality have been hindered by legacy sources of phosphorus added to storm water through transport to drainage systems by vegetation. Similarly, reductions in field erosion in agricultural watersheds have not led to major reductions in phosphorus transport, because of continued release of biological sources of P. Where management of phosphorus has been most effective in reducing eutrophication of lakes, decreases in N removal processes have led to long term increases in N concentration and transport. Together, these examples show important roles for biological processes affecting nutrient movement in highly modified landscapes. Consideration of the downstream physical and biological responses of management changes are thus critical toward identification of actions that will most effectively reduce excess nutrients watersheds and coastal zones.

  6. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    NASA Astrophysics Data System (ADS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  7. Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity.

    PubMed

    Habermeyer, Michael; Fritz, Jessica; Barthelmes, Hans U; Christensen, Morten O; Larsen, Morten K; Boege, Fritz; Marko, Doris

    2005-09-01

    In the present study, we investigated the effect of anthocyanidins on human topoisomerases I and II and its relevance for DNA integrity within human cells. Anthocyanidins bearing vicinal hydroxy groups at the B-ring (delphinidin, DEL; cyanidin, CY) were found to potently inhibit the catalytic activity of human topoisomerases I and II, without discriminating between the IIalpha and the IIbeta isoforms. However, in contrast to topoisomerase poisons, DEL and CY did not stabilize the covalent DNA-topoisomerase intermediates (cleavable complex) of topoisomerase I or II. Using recombinant topoisomerase I, the presence of CY or DEL (> or = 1 microM) effectively prohibited the stabilization of the cleavable complex by the topoisomerase I poison camptothecin. We furthermore investigated whether the potential protective effect vs topoisomerase I poisons is reflected also on the cellular level, affecting the DNA damaging properties of camptothecin. Indeed, in HT29 cells, low micromolar concentrations of DEL (1-10 microM) significantly diminished the DNA strand breaking effect of camptothecin (100 microM). However, at concentrations > or = 50 microM, all anthocyanidins tested (delphinidin, cyanidin, malvidin, pelargonidin, and paeonidin), including those not interfering with topoisomerases, were found to induce DNA strand breaks in the comet assay. All of these analogues were able to compete with ethidium bromide for the intercalation into calf thymus DNA and to replace the minor groove binder Hoechst 33258. These data indicate substantial affinity to double-stranded DNA, which might contribute at least to the DNA strand breaking effect of anthocyanidins at higher concentrations (> or = 50 microM).

  8. Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

    PubMed Central

    2011-01-01

    Background Viscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. Methods Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions. Results 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. Conclusions Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages. PMID:21871125

  9. Conditions for the successful integration of Human and Organizational Factors (HOF) in the nuclear safety analysis.

    PubMed

    Tosello, Michèle; Lévêque, Françoise; Dutillieu, Stéphanie; Hernandez, Guillaume; Vautier, Jean-François

    2012-01-01

    This communication presents some elements which come from the experience feedback at CEA about the conditions for the successful integration of HOF in the nuclear safety analysis. To point out some of these conditions, one of the concepts proposed by Edgar Morin to describe the functioning of "complex" systems: the dialogical principle has been used. The idea is to look for some dialogical pairs. The elements of this kind of pair are both complementary and antagonist to one another. Three dialogical pairs are presented in this communication. The first two pairs are related to the organization of the HOF network and the last one is related to the methods which are used to analyse the working situations. The three pairs are: specialist - non-specialist actors of the network, centralized - distributed human resources in the network and microscopic - macroscopic levels of HOF methods to analyse the working situations. To continuously improve these three dialogical pairs, it is important to keep the differences which exist between the two elements of a pair and to find and maintain a balance between the two elements of the pairs. PMID:22317122

  10. Conditions for the successful integration of Human and Organizational Factors (HOF) in the nuclear safety analysis.

    PubMed

    Tosello, Michèle; Lévêque, Françoise; Dutillieu, Stéphanie; Hernandez, Guillaume; Vautier, Jean-François

    2012-01-01

    This communication presents some elements which come from the experience feedback at CEA about the conditions for the successful integration of HOF in the nuclear safety analysis. To point out some of these conditions, one of the concepts proposed by Edgar Morin to describe the functioning of "complex" systems: the dialogical principle has been used. The idea is to look for some dialogical pairs. The elements of this kind of pair are both complementary and antagonist to one another. Three dialogical pairs are presented in this communication. The first two pairs are related to the organization of the HOF network and the last one is related to the methods which are used to analyse the working situations. The three pairs are: specialist - non-specialist actors of the network, centralized - distributed human resources in the network and microscopic - macroscopic levels of HOF methods to analyse the working situations. To continuously improve these three dialogical pairs, it is important to keep the differences which exist between the two elements of a pair and to find and maintain a balance between the two elements of the pairs.

  11. Velocity, safety, or both? How do balance and strength of goal conflicts affect drivers' behaviour, feelings and physiological responses?

    PubMed

    Schmidt-Daffy, Martin; Brandenburg, Stefan; Beliavski, Alina

    2013-06-01

    Motivational models of driving behaviour agree that choice of speed is modulated by drivers' goals. Whilst it is accepted that some goals favour fast driving and others favour safe driving, little is known about the interplay of these conflicting goals. In the present study, two aspects of this interplay are investigated: the balance of conflict and the strength of conflict. Thirty-two participants completed several simulated driving runs in which fast driving was rewarded with a monetary gain if the end of the track was reached. However, unpredictably, some runs ended with the appearance of a deer. In these runs, fast driving was punished with a monetary loss. The ratio between the magnitudes of gains and losses varied in order to manipulate the balance of conflict. The absolute magnitudes of both gains and losses altered the strength of conflict. Participants drove slower, reported an increase in anxiety-related feelings, and showed indications of physiological arousal if there was more money at stake. In contrast, only marginal effects of varying the ratio between gains and losses were observed. Results confirm that the strength of a safety-velocity conflict is an important determinant of drivers' behaviour, feelings, and physiological responses. The lack of evidence for the balance of conflict playing a role suggests that in each condition, participants subjectively weighted the loss higher than the gain (loss aversion). It is concluded that the interplay of the subjective values that drivers attribute to objective incentives for fast and safe driving is a promising field for future research. Incorporating this knowledge into motivational theories of driving behaviour might improve their contribution to the design of adequate road safety measures.

  12. A human liver microphysiology platform for investigating physiology, drug safety, and disease models

    PubMed Central

    Vernetti, Lawrence A.; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D. Lansing

    2015-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180μM troglitazone or 210μM nimesulide produced acute toxicity within 2–4 days, whereas 28μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600μM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related chemical

  13. A human liver microphysiology platform for investigating physiology, drug safety, and disease models.

    PubMed

    Vernetti, Lawrence A; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D Lansing

    2016-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 μM troglitazone or 210 μM nimesulide produced acute toxicity within 2-4 days, whereas 28 μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600 µM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30 nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related

  14. A human liver microphysiology platform for investigating physiology, drug safety, and disease models.

    PubMed

    Vernetti, Lawrence A; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D Lansing

    2016-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 μM troglitazone or 210 μM nimesulide produced acute toxicity within 2-4 days, whereas 28 μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600 µM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30 nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related

  15. Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

    PubMed Central

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

    2015-01-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  16. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections.

  17. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  18. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

    PubMed

    Davis, Kasey N; Tao, Ran; Li, Chao; Gao, Yuan; Gondré-Lewis, Marjorie C; Lipska, Barbara K; Shin, Joo Heon; Xie, Bin; Ye, Tianzhang; Weinberger, Daniel R; Kleinman, Joel E; Hyde, Thomas M

    2016-01-01

    Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders. PMID:26848839

  19. Artificial Box C/D RNAs Affect Pre-mRNA Maturation in Human Cells

    PubMed Central

    Stepanov, Grigoriy A.; Semenov, Dmitry V.; Savelyeva, Anna V.; Kuligina, Elena V.; Koval, Olga A.; Rabinov, Igor V.; Richter, Vladimir A.

    2013-01-01

    Box C/D small nucleolar RNAs (snoRNAs) are known to guide the 2′-O-ribose methylation of nucleotides in eukaryotic ribosomal RNAs and small nuclear RNAs. Recently snoRNAs are predicted to regulate posttranscriptional modifications of pre-mRNA. To expand understanding of the role of snoRNAs in control of gene expression, in this study we tested the ability of artificial box C/D RNAs to affect the maturation of target pre-mRNA. We found that transfection of artificial box C/D snoRNA analogues directed to HSPA8 pre-mRNAs into human cells induced suppression of the target mRNA expression in a time- and dose-dependent manner. The artificial box C/D RNA directed to the branch point adenosine of the second intron, as well as the analogue directed to the last nucleotide of the second exon of the HSPA8 pre-mRNA caused the most prominent influence on the level of HSPA8 mRNAs. Neither box D nor the ability to direct 2′-O-methylation of nucleotides in target RNA was essential for the knockdown activity of artificial snoRNAs. Inasmuch as artificial box C/D RNAs decreased viability of transfected human cells, we propose that natural snoRNAs as well as their artificial analogues can influence the maturation of complementary pre-mRNA and can be effective regulators of vital cellular processes. PMID:23607094

  20. Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells

    PubMed Central

    Kim, Hyun-Sung; Hoang, Michael; Tu, Thanh G.; Elie, Omid; Lee, Connie; Vu, Catherine; Horvath, Steve; Spigelman, Igor; Kim, Yong

    2014-01-01

    Stem cells, especially human embryonic stem cells (hESCs), are useful models to study molecular mechanisms of human disorders that originate during gestation. Alcohol (ethanol, EtOH) consumption during pregnancy causes a variety of prenatal and postnatal disorders collectively referred to as fetal alcohol spectrum disorders (FASDs). To better understand the molecular events leading to FASDs, we performed a genome-wide analysis of EtOH's effects on the maintenance and differentiation of hESCs in culture. Gene Co-expression Network Analysis showed significant alterations in gene profiles of EtOH-treated differentiated or undifferentiated hESCs, particularly those associated with molecular pathways for metabolic processes, oxidative stress, and neuronal properties of stem cells. A genome-wide DNA methylome analysis revealed widespread EtOH-induced alterations with significant hypermethylation of many regions of chromosomes. Undifferentiated hESCs were more vulnerable to EtOH's effect than their differentiated counterparts, with methylation on the promoter regions of chromosomes 2, 16 and 18 in undifferentiated hESCs most affected by EtOH exposure. Combined transcriptomic and DNA methylomic analysis produced a list of differentiation-related genes dysregulated by EtOH-induced DNA methylation changes, which likely play a role in EtOH-induced decreases in hESC pluripotency. DNA sequence motif analysis of genes epigenetically altered by EtOH identified major motifs representing potential binding sites for transcription factors. These findings should help in deciphering the precise mechanisms of alcohol-induced teratogenesis. PMID:24751885

  1. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

    PubMed

    Davis, Kasey N; Tao, Ran; Li, Chao; Gao, Yuan; Gondré-Lewis, Marjorie C; Lipska, Barbara K; Shin, Joo Heon; Xie, Bin; Ye, Tianzhang; Weinberger, Daniel R; Kleinman, Joel E; Hyde, Thomas M

    2016-01-01

    Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

  2. Bisphosphonates modulate vital functions of human osteoblasts and affect their interactions with breast cancer cells.

    PubMed

    Kaiser, Tatjana; Teufel, Ingrid; Geiger, Konstanze; Vater, Yvonne; Aicher, Wilhelm K; Klein, Gerd; Fehm, Tanja

    2013-07-01

    Bisphosphonates (BPs) are in clinical use for the treatment of breast cancer patients with bone metastases. Their anti-resorptive effect is mainly explained by inhibition of osteoclast activity, but recent evidence also points to a direct action of BPs on bone-forming osteoblasts. However, the mechanisms how BPs influence osteoblasts and their interactions with breast cancer cells are still poorly characterized. Human osteoblasts isolated from bone specimens were characterized in depth by their expression of osteogenic marker genes. The influence of the nitrogen-containing BPs zoledronate (Zol), ibandronate (Iban), and pamidronate (Pam) on molecular and cellular functions of osteoblasts was assessed focusing on cell proliferation and viability, apoptosis, cytokine secretion, and osteogenic-associated genes. Furthermore, effects of BPs on osteoblast-breast tumor cell interactions were examined in an established in vitro model system. The BPs Zol and Pam inhibited cell viability of osteoblasts. This effect was mediated by an induction of caspase-dependent apoptosis in osteoblasts. By interfering with the mevalonate pathway, Zol also reduces the proliferation of osteoblasts. The expression of phenotypic markers of osteogenic differentiation was altered by Zol and Pam. In addition, both BPs strongly influenced the secretion of the chemokine CCL2 by osteoblasts. Breast cancer cells also responded to Zol and Pam with a reduced cell adhesion to osteoblast-derived extracellular matrix molecules and with a decreased migration in response to osteoblast-secreted factors. BPs revealed prominent effects on human osteoblasts. Zol and Pam as the most potent BPs affected not only the expression of osteogenic markers, osteoblast viability, and proliferation but also important osteoblast-tumor cell interactions. Changing the osteoblast metabolism by BPs modulates migration and adhesion of breast cancer cells as well. PMID:23807419

  3. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

    PubMed

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  4. Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

    PubMed Central

    Chang, Ming-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-01-01

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5–10 μm) having higher endotoxin levels than did fine particles (0.5–2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers. PMID:24368426

  5. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders

    PubMed Central

    Li, Chao; Gao, Yuan; Gondré-Lewis, Marjorie C.; Lipska, Barbara K.; Shin, Joo Heon; Xie, Bin; Ye, Tianzhang; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.

    2016-01-01

    Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders. PMID:26848839

  6. CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro.

    PubMed

    Wei, Xiaowei; Liu, Shuai; Wang, Xiaoqi; Yan, Qiu

    2012-03-01

    Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function. PMID:22393164

  7. Oxidized Low Density Lipoprotein (LDL) Affects Hyaluronan Synthesis in Human Aortic Smooth Muscle Cells*

    PubMed Central

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N.; Hascall, Vincent C.; De Luca, Giancarlo; Passi, Alberto

    2013-01-01

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20–50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL. PMID:23979132

  8. Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells.

    PubMed

    Akhtar Ali, Muhammad; Younis, Shady; Wallerman, Ola; Gupta, Rajesh; Andersson, Leif; Sjöblom, Tobias

    2015-06-23

    The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle-related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

  9. Understanding the relationship between safety investment and safety performance of construction projects through agent-based modeling.

    PubMed

    Lu, Miaojia; Cheung, Clara Man; Li, Heng; Hsu, Shu-Chien

    2016-09-01

    The construction industry in Hong Kong increased its safety investment by 300% in the past two decades; however, its accident rate has plateaued to around 50% for one decade. Against this backdrop, researchers have found inconclusive results on the causal relationship between safety investment and safety performance. Using agent-based modeling, this study takes an unconventional bottom-up approach to study safety performance on a construction site as an outcome of a complex system defined by interactions among a worksite, individual construction workers, and different safety investments. Instead of focusing on finding the absolute relationship between safety investment and safety performance, this study contributes to providing a practical framework to investigate how different safety investments interacting with different parameters such as human and environmental factors could affect safety performance. As a result, we could identify cost-effective safety investments under different construction scenarios for delivering optimal safety performance.

  10. Understanding the relationship between safety investment and safety performance of construction projects through agent-based modeling.

    PubMed

    Lu, Miaojia; Cheung, Clara Man; Li, Heng; Hsu, Shu-Chien

    2016-09-01

    The construction industry in Hong Kong increased its safety investment by 300% in the past two decades; however, its accident rate has plateaued to around 50% for one decade. Against this backdrop, researchers have found inconclusive results on the causal relationship between safety investment and safety performance. Using agent-based modeling, this study takes an unconventional bottom-up approach to study safety performance on a construction site as an outcome of a complex system defined by interactions among a worksite, individual construction workers, and different safety investments. Instead of focusing on finding the absolute relationship between safety investment and safety performance, this study contributes to providing a practical framework to investigate how different safety investments interacting with different parameters such as human and environmental factors could affect safety performance. As a result, we could identify cost-effective safety investments under different construction scenarios for delivering optimal safety performance. PMID:27240124

  11. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    SciTech Connect

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-02-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  12. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults

    PubMed Central

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2015-01-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. PMID:26563978

  13. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

    PubMed

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2016-02-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

  14. Immunosuppressive drugs affect high-mannose/hybrid N-glycans on human allostimulated leukocytes.

    PubMed

    Pocheć, Ewa; Bocian, Katarzyna; Ząbczyńska, Marta; Korczak-Kowalska, Grażyna; Lityńska, Anna

    2015-01-01

    N-glycosylation plays an important role in the majority of physiological and pathological processes occurring in the immune system. Alteration of the type and abundance of glycans is an element of lymphocyte differentiation; it is also common in the development of immune-mediated inflammatory diseases. The N-glycosylation process is very sensitive to different environmental agents, among them the pharmacological environment of immunosuppressive drugs. Some results show that high-mannose oligosaccharides have the ability to suppress different stages of the immune response. We evaluated the effects of cyclosporin A (CsA) and rapamycin (Rapa) on high-mannose/hybrid-type glycosylation in human leukocytes activated in a two-way mixed leukocyte reaction (MLR). CsA significantly reduced the number of leukocytes covered by high-mannose/hybrid N-glycans, and the synergistic action of CsA and Rapa led to an increase of these structures on the remaining leukocytes. This is the first study indicating that β1 and β3 integrins bearing high-mannose/hybrid structures are affected by Rapa and CsA. Rapa taken separately and together with CsA changed the expression of β1 and β3 integrins and, by regulating the protein amount, increased the oligomannose/hybrid-type N-glycosylation on the leukocyte surface. We suggest that the changes in the glycosylation profile of leukocytes may promote the development of tolerance in transplantation.

  15. PMCA activity and membrane tubulin affect deformability of erythrocytes from normal and hypertensive human subjects.

    PubMed

    Monesterolo, Noelia E; Nigra, Ayelen D; Campetelli, Alexis N; Santander, Verónica S; Rivelli, Juan F; Arce, Carlos A; Casale, Cesar H

    2015-11-01

    Our previous studies demonstrated formation of a complex between acetylated tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the lipid environment on structure of this complex and on PMCA activity. Deformability of erythrocytes from hypertensive human subjects was reduced by an increase in membrane tubulin content. In the present study, we examined the regulation of PMCA activity by tubulin in normotensive and hypertensive erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings were that: (i) PMCA was associated with tubulin in normotensive and hypertensive erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte deformability, and (iii) when tubulin was present in the erythrocyte membrane, treatment with DAG or PA led to increased deformability and associated PMCA activity. Taken together, our findings indicate that PMCA activity is involved in deformability of both normotensive and hypertensive erythrocytes. This rheological property of erythrocytes is affected by acetylated tubulin and its lipid environment because both regulate PMCA activity.

  16. African dust carries microbes across the ocean: are they affecting human and ecosystem health?

    USGS Publications Warehouse

    Kellogg, Christina A.; Griffin, Dale W.

    2003-01-01

    Atmospheric transport of dust from northwest Africa to the western Atlantic Ocean region may be responsible for a number of environmental hazards, including the demise of Caribbean corals; red tides; amphibian diseases; increased occurrence of asthma in humans; and oxygen depletion (eutrophication) in estuaries. Studies of satellite images suggest that hundreds of millions of tons of dust are trans-ported annually at relatively low altitudes across the Atlantic Ocean to the Caribbean Sea and southeastern United States. The dust emanates from the expanding Sahara/Sahel desert region in Africa and carries a wide variety of bacteria and fungi. The U.S. Geological Survey, in collaboration with the NASA/Goddard Spaceflight Center, is conducting a study to identify microbes--bacteria, fungi, viruses--transported across the Atlantic in African soil dust. Each year, millions of tons of desert dust blow off the west African coast and ride the trade winds across the ocean, affecting the entire Caribbean basin, as well as the southeastern United States. Of the dust reaching the U.S., Florida receives about 50 percent, while the rest may range as far north as Maine or as far west as Colorado. The dust storms can be tracked by satellite and take about one week to cross the Atlantic.

  17. Molecular basis of human transcobalamin II deficiency in an affected family

    SciTech Connect

    Li, N.; Seetharam, S.; Seetharam, B.

    1994-09-01

    Transcobalamin II (TC II) deficiency is an autosomal recessive disease leading to cobalamin (Cbl, Vitamin B{sub 12}) deficiency. Patients with this disorder fail to absorb and transport Cbl across cellular membranes and develop Cbl deficiency, symptoms of which include failure to thrive, megaloblastic anemia, impaired immunodefence and neurological disorders. The molecular basis for this disease is not known. By means of Southern blotting and sequence analysis of TC II, cDNA amplified from fibroblasts of an affected child and his parents, we have identified two mutant TC II alleles. The maternally derived allele had a gross deletion, while the paternally derived allele had a 4-nucleotide ({sup 1023}TCTG) deletion which caused a reading frame shift and generation of a premature termination codon, 146 nucleotides downstream from the deletion. Both these deletions caused markedly reduced levels of TC II mRNA and protein. In addition, these two deletions were unique to this family and were not detected in four other unrelated TC II deficient patients who also exhibited the same (TC II protein/mRNA deficiency) phenotypes. Based on this study we suggest, (1) that the molecular defect in the most common form of human TC II deficiency (lack of immunoprecipitable plasma TC II) is heterogeneous and (2) these mutations cause TC II mRNA and protein deficiency leading to defective plasma transport of Cbl and the development of Cbl deficiency.

  18. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    PubMed

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  19. A dynamic evolution model of human opinion as affected by advertising

    NASA Astrophysics Data System (ADS)

    Luo, Gui-Xun; Liu, Yun; Zeng, Qing-An; Diao, Su-Meng; Xiong, Fei

    2014-11-01

    We propose a new model to investigate the dynamics of human opinion as affected by advertising, based on the main idea of the CODA model and taking into account two practical factors: one is that the marginal influence of an additional friend will decrease with an increasing number of friends; the other is the decline of memory over time. Simulations show several significant conclusions for both advertising agencies and the general public. A small difference of advertising’s influence on individuals or advertising coverage will result in significantly different advertising effectiveness within a certain interval of value. Compared to the value of advertising’s influence on individuals, the advertising coverage plays a more important role due to the exponential decay of memory. Meanwhile, some of the obtained results are in accordance with people’s daily cognition about advertising. The real key factor in determining the success of advertising is the intensity of exchanging opinions, and people’s external actions always follow their internal opinions. Negative opinions also play an important role.

  20. Characterization of human arterial tissue affected by atherosclerosis using multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Baria, Enrico; Cicchi, Riccardo; Rotellini, Matteo; Nesi, Gabriella; Massi, Daniela; Pavone, Francesco S.

    2016-03-01

    Atherosclerosis is a widespread cardiovascular disease caused by the deposition of lipids (such as cholesterol and triglycerides) on the inner arterial wall. The rupture of an atherosclerotic plaque, resulting in a thrombus, is one of the leading causes of death in the Western World. Preventive assessment of plaque vulnerability is therefore extremely important and can be performed by studying collagen organization and lipid composition in atherosclerotic arterial tissues. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Instead, a label-free and non-invasive alternative is provided by nonlinear microscopy. In this study, we combined SHG and FLIM microscopy in order to characterize collagen organization and lipids in human carotid ex vivo tissues affected by atherosclerosis. SHG and TPF images, acquired from different regions within atherosclerotic plaques, were processed through image pattern analysis methods (FFT, GLCM). The resulting information on collagen and cholesterol distribution and anisotropy, combined with collagen and lipids fluorescence lifetime measured from FLIM images, allowed characterization of carotid samples and discrimination of different tissue regions. The presented method can be applied for automated classification of atherosclerotic lesions and plaque vulnerability. Moreover, it lays the foundation for a potential in vivo diagnostic tool to be used in clinical setting.

  1. Trace metals in sediments of a Mediterranean estuary affected by human activities (Acheloos river estuary, Greece).

    PubMed

    Dassenakis, M; Degaita, A; Scoullos, M

    1995-05-19

    Trace metals were studied in the sediments of the ecologically, economically and scientifically important estuary of the Acheloos river, in western Greece. Human activities (dams, agriculture, traffic, etc.) influence the estuarine system of Acheloos and in combination with the hydrological, mineralogical and morphological characteristics of the estuary affect the chemical behaviour and the distribution patterns of trace metals in its sediments. The large scale disturbance of the system is imminent in the near future as it is planned to divert approximately 50% of the river water. A study of the distribution patterns of trace metals revealed that in the estuary there are zones with different metal levels. The concentrations of most metals (Al, Fe, Cu, Ni, Zn) are elevated in three of these zones (upstream, sill, seawards). A different behaviour was observed for Mn due to its association with carbonates that were observed in significant concentrations throughout the estuarine zone. A sequential extraction procedure, applied to the sediments, indicated low percentages of easily exchangeable metals, increased mobility of Cu and Zn and increased association of Ni, Cr and Fe with the aluminosilicate lattice. Although the river is not considered to be heavily polluted, some metals have shown an enrichment in the surface sediments as a result of general anthropogenic activities not derived from point sources.

  2. Cell culture density affects the proliferation activity of human adipose tissue stem cells.

    PubMed

    Kim, Dae Seong; Lee, Myoung Woo; Ko, Young Jong; Chun, Yong Hoon; Kim, Hyung Joon; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-01-01

    In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions.

  3. Immunosuppressive Drugs Affect High-Mannose/Hybrid N-Glycans on Human Allostimulated Leukocytes

    PubMed Central

    Pocheć, Ewa; Bocian, Katarzyna; Ząbczyńska, Marta; Korczak-Kowalska, Grażyna; Lityńska, Anna

    2015-01-01

    N-glycosylation plays an important role in the majority of physiological and pathological processes occurring in the immune system. Alteration of the type and abundance of glycans is an element of lymphocyte differentiation; it is also common in the development of immune-mediated inflammatory diseases. The N-glycosylation process is very sensitive to different environmental agents, among them the pharmacological environment of immunosuppressive drugs. Some results show that high-mannose oligosaccharides have the ability to suppress different stages of the immune response. We evaluated the effects of cyclosporin A (CsA) and rapamycin (Rapa) on high-mannose/hybrid-type glycosylation in human leukocytes activated in a two-way mixed leukocyte reaction (MLR). CsA significantly reduced the number of leukocytes covered by high-mannose/hybrid N-glycans, and the synergistic action of CsA and Rapa led to an increase of these structures on the remaining leukocytes. This is the first study indicating that β1 and β3 integrins bearing high-mannose/hybrid structures are affected by Rapa and CsA. Rapa taken separately and together with CsA changed the expression of β1 and β3 integrins and, by regulating the protein amount, increased the oligomannose/hybrid-type N-glycosylation on the leukocyte surface. We suggest that the changes in the glycosylation profile of leukocytes may promote the development of tolerance in transplantation. PMID:26339568

  4. Calcium signalling in human neutrophil cell lines is not affected by low-frequency electromagnetic fields.

    PubMed

    Golbach, Lieke A; Philippi, John G M; Cuppen, Jan J M; Savelkoul, Huub F J; Verburg-van Kemenade, B M Lidy

    2015-09-01

    We are increasingly exposed to low-frequency electromagnetic fields (LF EMFs) by electrical devices and power lines, but if and how these fields interact with living cells remains a matter of debate. This study aimed to investigate the potential effect of LF EMF exposure on calcium signalling in neutrophils. In neutrophilic granulocytes, activation of G-protein coupled receptors leads to efflux of calcium from calcium stores and influx of extracellular calcium via specialised calcium channels. The cytoplasmic rise of calcium induces cytoskeleton rearrangements, modified gene expression patterns, and cell migration. If LF EMF modulates intracellular calcium signalling, this will influence cellular behaviour and may eventually lead to health problems. We found that calcium mobilisation upon chemotactic stimulation was not altered after a short 30 min or long-term LF EMF exposure in human neutrophil-like cell lines HL-60 or PLB-985. Neither of the two investigated wave forms (Immunent and 50 Hz sine wave) at three magnetic flux densities (5 μT, 300 μT, and 500 μT) altered calcium signalling in vitro. Gene-expression patterns of calcium-signalling related genes also did not show any significant changes after exposure. Furthermore, analysis of the phenotypical appearance of microvilli by scanning electron microscopy revealed no alterations induced by LF EMF exposure. The findings above indicate that exposure to 50 Hz sinusoidal or Immunent LF EMF will not affect calcium signalling in neutrophils in vitro.

  5. Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans

    PubMed Central

    Ekström, Mattias; Söderberg, Stefan; Tornvall, Per

    2015-01-01

    Adipose tissue (AT), classically thought to be merely an energy store, has been shown to produce inflammatory and metabolically active cytokines. Recently, adiponectin and leptin, adipokines primarily synthesized by adipocytes, have attracted considerable attention because inflammation has been suggested to modulate adipokine levels. However, the regulation of adiponectin and leptin is complex and the knowledge about their synthesis within the early onset of inflammation is poorly understood. The aim of this study was to investigate if the synthesis of adiponectin and leptin is affected during the early phase of an acute systemic inflammation. Eighteen healthy subjects were allocated to vaccination against Salmonella typhi or to a control group, and adiponectin and leptin concentrations measured in plasma during 24 h. Nine patients, without markers of inflammation, undergoing open heart surgery were investigated before and after the operation by analysis of plasma levels and AT gene expression of adiponectin and leptin. Plasma interleukin (IL)-6 concentrations were measured in both cohorts. Plasma levels of IL-6 were doubled after vaccination and increased 30-fold after open heart surgery. Plasma levels of adiponectin and leptin were unchanged after vaccination whereas adiponectin and leptin tended to decrease after surgery. The gene expression of adiponectin and leptin was unaltered in omental and subcutaneous AT after surgery. Despite the use of two models of stimulated in vivo systemic inflammation, we found no evidence of an early regulation of adiponectin and leptin synthesis, indicating that these two adipokines are not key elements in an acute systemic inflammation in humans. PMID:26664879

  6. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

    PubMed Central

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  7. Automation of closed environments in space for human comfort and safety

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This report culminates the work accomplished during a three year design project on the automation of an Environmental Control and Life Support System (ECLSS) suitable for space travel and colonization. The system would provide a comfortable living environment in space that is fully functional with limited human supervision. A completely automated ECLSS would increase astronaut productivity while contributing to their safety and comfort. The first section of this report, section 1.0, briefly explains the project, its goals, and the scheduling used by the team in meeting these goals. Section 2.0 presents an in-depth look at each of the component subsystems. Each subsection describes the mathematical modeling and computer simulation used to represent that portion of the system. The individual models have been integrated into a complete computer simulation of the CO2 removal process. In section 3.0, the two simulation control schemes are described. The classical control approach uses traditional methods to control the mechanical equipment. The expert control system uses fuzzy logic and artificial intelligence to control the system. By integrating the two control systems with the mathematical computer simulation, the effectiveness of the two schemes can be compared. The results are then used as proof of concept in considering new control schemes for the entire ECLSS. Section 4.0 covers the results and trends observed when the model was subjected to different test situations. These results provide insight into the operating procedures of the model and the different control schemes. The appendix, section 5.0, contains summaries of lectures presented during the past year, homework assignments, and the completed source code used for the computer simulation and control system.

  8. P50 suppression in human discrimination fear conditioning paradigm using danger and safety signals.

    PubMed

    Kurayama, Taichi; Matsuzawa, Daisuke; Komiya, Zen; Nakazawa, Ken; Yoshida, Susumu; Shimizu, Eiji

    2012-04-01

    Auditory P50 suppression, which is assessed using a paired auditory stimuli (S1 and S2) paradigm to record the P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were observed in patients with anxiety disorders, including panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder, as we previously reported. The processes of fear conditioning are thought to play a role in the pathophysiology of anxiety disorders. In addition, we found that the P50 sensory gating mechanism might be physiologically associated with fear conditioning and extinction in a simple human fear-conditioning paradigm that involved a light signal as a conditioned stimulus (CS+). Our objective was to investigate the different patterns of P50 suppression in a discrimination fear-conditioning paradigm with both a CS+ (danger signal) and a CS- (safety signal). Twenty healthy volunteers were recruited. We measured the auditory P50 suppression in the control (baseline) phase, in the fear-acquisition phase, and in the fear-extinction phase using a discrimination fear-conditioning paradigm. Two-way (CSs vs. phase) Analysis of variance with repeated measures demonstrated a significant interaction between the two factors. Post-hoc LSD analysis indicated that the P50 S2/S1 ratio in the CS+ acquisition phase was significantly higher than that in the CS- acquisition phase. These results suggest that the auditory P50 sensory gating might differ according to the cognition of the properties (potentially dangerous or safe) of the perceived signal.

  9. Issues for resolving adverse effects on the safety culture of human work underload and workload transitions in complex human-machine systems

    SciTech Connect

    Ryan, T.G.

    1996-08-01

    A workshop was conducted whose specific purpose was to build on earlier work of the US National Research Council, US federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded safety performance in advanced human-machine systems(e.g., nuclear production, transportation, aerospace) due to human work underload and workload transition, and (2) develop strategies for resolving these issues. The workshop affirmed that: (1) work underload and workload transition are issues that will have to be addressed by designers of advanced human-machine systems, especially those relying on automation, if cost, performance, safety, and operator acceptability are to be optimized, (2) human machine allocation models, standards and guidelines which go beyond simple capability approaches will be needed to preclude or seriously diminish the work underload and workload transition problems, and (3) the 16 workload definition, measurement, situational awareness, and trust issues identified during the workshop, need resolution if these models, standards, and guidelines are to be achieved.

  10. An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Goodman, Allen; Hooley, Becky L.

    2003-01-01

    An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

  11. Human serum butyrylcholinesterase: in vitro and in vivo stability, pharmacokinetics, and safety in mice.

    PubMed

    Saxena, Ashima; Sun, Wei; Luo, Chunyuan; Doctor, Bhupendra P

    2005-12-15

    The use of exogenously administered cholinesterases (ChEs) as bioscavengers of highly toxic organophosphate (OP) nerve agents is now sufficiently well documented to make them a highly viable prophylactic treatment against this potential threat. Of the ChEs evaluated so far, human serum butyrylcholinesterase (HuBChE) is most suitable for human use. A dose of 200 mg (3 mg/kg) of HuBChE is envisioned as a prophylactic treatment in humans that can protect from an exposure of up to 2 x LD50 of soman. In addition to its use as a prophylactic for a variety of wartime scenarios, including covert actions, it also has potential use for first responders (civilians) reacting to terrorist nerve gas release. We recently, developed a procedure for the large-scale purification of HuBChE, which yielded approximately 6 g of highly purified enzyme from 120 kg of Cohn fraction IV-4. The enzyme had a specific activity of 700-750 U/mg and migrated as a single band on SDS-PAGE. To provide data for initiating an investigational new drug (IND) application for the use of this enzyme as a bioscavenger in humans, we established its pharmacokinetic properties, examined its safety in mice, and evaluated its shelf life at various temperatures. In mice administered various doses up to 90 mg/kg, enzyme activity reached peak levels in circulation at 10 and 24 h following i.p. and i.m. injections, respectively. The enzyme displayed a mean residence time (MRT) of 40-50 h, regardless of the route of administration or dose of injected enzyme. Mice were euthanized 2 weeks following enzyme administration and tissues were examined grossly or microscopically for possible toxic effects. Results suggest that HuBChE does not exhibit any toxicity in mice as measured by general observation, serum chemistry, hematology, gross or histologic tissue changes. The shelf life of this enzyme stored at 4, 25, 37, and 45 degrees C was determined in lyophilized form. The enzyme was found to be stable when stored in

  12. Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.

    PubMed

    Sugai, Keiko; Fukuzawa, Ryuji; Shofuda, Tomoko; Fukusumi, Hayato; Kawabata, Soya; Nishiyama, Yuichiro; Higuchi, Yuichiro; Kawai, Kenji; Isoda, Miho; Kanematsu, Daisuke; Hashimoto-Tamaoki, Tomoko; Kohyama, Jun; Iwanami, Akio; Suemizu, Hiroshi; Ikeda, Eiji; Matsumoto, Morio; Kanemura, Yonehiro; Nakamura, Masaya; Okano, Hideyuki

    2016-01-01

    The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs. PMID:27642008

  13. The refinement of uncertainty/safety factors in risk assessment by the incorporation of data on toxicokinetic variability in humans.

    PubMed

    Dorne, J L C M; Renwick, A G

    2005-07-01

    The derivation of safe levels of exposure in humans for compounds that are assumed to cause threshold toxicity has relied on the application of a 100-fold uncertainty factor to a measure for the threshold, such as the no observed adverse effect level (NOAEL) or the benchmark dose (BMD). This 100-fold safety factor consists of the product of two 10-fold factors allowing for human variability and interspecies differences. The International Programme on Chemical Safety has suggested the subdivision of these 10-fold factors to allow for variability in toxicokinetics and toxicodynamics. This subdivision allows the replacement of the default uncertainty factors with a chemical-specific adjustment factor (CSAF) when suitable data are available. This short review describes potential options to refine safety factors used in risk assessment, with particular emphasis on pathway-related uncertainty factors associated with variability in kinetics. These pathway-related factors were derived from a database that quantified interspecies differences and human variability in phase I metabolism, phase II metabolism, and renal excretion. This approach allows metabolism and pharmacokinetic data in healthy adults and subgroups of the population to be incorporated in the risk-assessment process and constitutes an intermediate approach between simple default factors and chemical-specific adjustment factors. PMID:15800035

  14. The refinement of uncertainty/safety factors in risk assessment by the incorporation of data on toxicokinetic variability in humans.

    PubMed

    Dorne, J L C M; Renwick, A G

    2005-07-01

    The derivation of safe levels of exposure in humans for compounds that are assumed to cause threshold toxicity has relied on the application of a 100-fold uncertainty factor to a measure for the threshold, such as the no observed adverse effect level (NOAEL) or the benchmark dose (BMD). This 100-fold safety factor consists of the product of two 10-fold factors allowing for human variability and interspecies differences. The International Programme on Chemical Safety has suggested the subdivision of these 10-fold factors to allow for variability in toxicokinetics and toxicodynamics. This subdivision allows the replacement of the default uncertainty factors with a chemical-specific adjustment factor (CSAF) when suitable data are available. This short review describes potential options to refine safety factors used in risk assessment, with particular emphasis on pathway-related uncertainty factors associated with variability in kinetics. These pathway-related factors were derived from a database that quantified interspecies differences and human variability in phase I metabolism, phase II metabolism, and renal excretion. This approach allows metabolism and pharmacokinetic data in healthy adults and subgroups of the population to be incorporated in the risk-assessment process and constitutes an intermediate approach between simple default factors and chemical-specific adjustment factors.

  15. Design of an LED-based sensor system to distinguish human skin from workpieces in safety applications.

    PubMed

    Schwaneberg, Oliver; Steiner, Holger; Bolívar, Peter Haring; Jung, Norbert

    2012-04-20

    Commercial light curtains use a technique known as muting to differentiate between work pieces and other objects (e.g., human limbs) based on precise model knowledge of the process. At manually fed machinery (e.g., bench saws), such precise models cannot be derived due to the way the machinery is used. This paper presents a multispectral scanning sensor to classify an object's surface material as a new approach for the problem. The system is meant to detect the presence of limbs and therefore optimized for human skin detection. Evaluation on a test set of skin and (wet) wood samples showed a sufficiently high reliability with respect to safety standards.

  16. Initial Assessment of Sulfur-Iodine Process Safety Issues and How They May Affect Pilot Plant Design and Operation

    SciTech Connect

    Robert S. Cherry

    2006-09-01

    The sulfur-iodine process to make hydrogen by the thermochemical splitting of water is under active development as part of a U.S. Department of Energy program. An integrated lab scale system is currently being designed and built. The next planned stage of development is a pilot plant with a thermal input of about 500 kW, equivalent to about 30,000 standard liters per hour of hydrogen production. The sulfur-iodine process contains a variety of hazards, including temperatures up to 850 ºC and hazardous chemical species including SO2, H2SO4, HI, I2, and of course H2. The siting and design of a pilot plant must consider these and other hazards. This report presents an initial analysis of the hazards that might affect pilot plant design and should be considered in the initial planning. The general hazards that have been identified include reactivity, flammability, toxicity, pressure, electrical hazards, and industrial hazards such as lifting and rotating equipment. Personnel exposure to these hazards could occur during normal operations, which includes not only running the process at the design conditions but also initial inventory loading, heatup, startup, shutdown, and system flushing before equipment maintenance. Because of the complexity and severity of the process, these ancillary operations are expected to be performed frequently. In addition, personnel could be exposed to the hazards during various abnormal situations which could include unplanned phase changes of liquids or solids, leaks of process fluids or cooling water into other process streams, unintentional introducion of foreign species into the process, and unexpected side reactions. Design of a pilot plant will also be affected by various codes and regulations such as the International Building Code, the International Fire Code, various National Fire Protection Association Codes, and the Emergency Planning and Community Right-to-Know Act.

  17. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

    PubMed Central

    Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

    2014-01-01

    Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose

  18. Modulators affecting the immune dialogue between human immune and colon cancer cells

    PubMed Central

    Djaldetti, Meir; Bessler, Hanna

    2014-01-01

    The link between chronic inflammation and colorectal cancer has been well established. The events proceeding along tumorigenesis are complicated and involve cells activated at the cancer microenvironment, tumor infiltrating polymorphonuclears, immune cells including lymphocyte subtypes and peripheral blood mononuclear cells (PBMC), as well as tumor-associated macrophages. The immune cells generate inflammatory cytokines, several of them playing a crucial role in tumorigenesis. Additional factors, such as gene expression regulated by cytokines, assembling of tumor growth- and transforming factors, accelerated angiogenesis, delayed apoptosis, contribute all to initiation, development and migration of tumor cells. Oxygen radical species originating from the inflammatory area promote cell mutation and cancer proliferation. Tumor cells may over-express pro-inflammatory mediators that in turn activate immune cells for inflammatory cytokines production. Consequently, an immune dialogue emerges between immune and cancer cells orchestrated through a number of activated molecular pathways. Cytokines, encompassing migration inhibitory factor, transforming growth factor beta 1, tumor necrosis factor-α, Interleukin (IL)-6, IL-10, IL-12, IL-17, IL-23 have been reported to be involved in human cancer development. Some cytokines, namely IL-5, IL-6, IL-10, IL-22 and growth factors promote tumor development and metastasis, and inhibit apoptosis via activation of signal transducer activator transcription-3 transcription factor. Colon cancer environment comprises mesenchymal, endothelial and immune cells. Assessment of the interaction between components in the tumor environment and malignant cells requires a reconsideration of a few topics elucidating the role of chronic inflammation in carcinogenesis, the function of the immune cells expressed by inflammatory cytokine production, the immunomodulation of cancer cells and the existence of a cross-talk between immune and malignant

  19. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.

    PubMed

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J; Cook, Edwin; Das, Soma; Ratain, Mark J

    2014-10-15

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.

  20. Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability

    SciTech Connect

    Huang, Xiao; Gibson, Lydia M.; Bell, Brittnaie J.; Lovelace, Leslie L.; Pea, Maria Marjorette O.; Berger, Franklin G.; Berger, Sondra H.; Lebioda, Lukasz

    2010-11-03

    Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of {approx}27 amino acids that is not present in bacterial TSs. The extension, which is disordered in all reported crystal structures of TSs, has been considered to play a primary role in protein turnover but not in catalytic activity. In mammalian cells, the variant V3A has a half-life similar to that of wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have half-lives approximately half of that for wt hTS. Catalytic turnover rates for most Val3 mutants are only slightly diminished, as expected. However, two mutants, V3L and V3F, have strongly compromised dUMP binding, with K{sub m,app} values increased by factors of 47 and 58, respectively. For V3L, this observation can be explained by stabilization of the inactive conformation of the loop of residues 181-197, which prevents substrate binding. In the crystal structure of V3L, electron density corresponding to a leucine residue is present in a position that stabilizes the loop of residues 181-197 in the inactive conformation. Since this density is not observed in other mutants and all other leucine residues are ordered in this structure, it is likely that this density represents Leu3. In the crystal structure of a V3F {center_dot} FdUMP binary complex, the nucleotide is bound in an alternative mode to that proposed for the catalytic complex, indicating that the high K{sub m,app} value is caused not by stabilization of the inactive conformer but by substrate binding in a nonproductive, inhibitory site. These observations show that the N-terminal extension affects the conformational state of the hTS catalytic region. Each of the mechanisms leading to the high K{sub m,app} values can be exploited to facilitate design of compounds acting as allosteric inhibitors of hTS.

  1. Mir-373 affects human lung cancer cells' growth and its E-cadherin expression.

    PubMed

    Wu, Weihua; He, Xiaoyan; Kong, Jing; Ye, Bin

    2012-01-01

    The aims of this study was to elucidate whether the expression of E-cadherin can be affected by the recombinant has-mir-373 eukaryotic expression plasmid vector through tests in vitro, and to analyze the relationship between the expression of E-cadherin and tumor growth. According to the has-mir-373 sequence in miRBase database, two template DNA sequences were designed. The has-mir-373 sequence and a control sequence were synthesized and cloned into pGenesil-1 eukaryotic expression plasmid vector. The recombinant plasmids were transfected into human lung cancer A549 cells by liposome-mediated method. The mir-373 expression in A549 cells was detected by using real-time quantitative polymerase chain reaction (real-time PCR). MTT (methyl thiazolyl tetrazolium) was used to analyze the growth of cancer cell cycle. RT-PCR and Western blotting were used to evaluate the levels of E-cadherin mRNA and protein expression, respectively. The expression of E-cadherin in cells was determined by immunocytochemistry. The mobility capability of transfected cells were evaluated by using wound healing assay in vitro. The fluorescent light was observed under fluorescent microscope. RT-PCR indicated that the mRNA of E-cadherin increased, and the Western blotting results also displayed that mir-373 promoted the expression of the E-cadherin protein. Compared with the control groups, MTT method and wound healing assay demonstrated that both the growth rate and migration of A549 cells transfected with the recombinant has-mir-373 eukaryotic expression plasmid was also decreased significantly (p < 0.001). The differences between the other two control groups were not significant (p > 0.05). The immunocytochemistry demonstrated a significant increase of E-cadherin protein levels in the cells transfected with mir-373, but not in the cells of the control group. Mir-373 could increase the expression levels of the E-cadherin and decrease the migration ability of human lung cancer A549 cells in

  2. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.

    PubMed

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J; Cook, Edwin; Das, Soma; Ratain, Mark J

    2014-10-15

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs. PMID:24879639

  3. Replacement of Val3 in human thymidylate synthase affects its kinetic properties and intracellular stability .

    PubMed

    Huang, Xiao; Gibson, Lydia M; Bell, Brittnaie J; Lovelace, Leslie L; Peña, Maria Marjorette O; Berger, Franklin G; Berger, Sondra H; Lebioda, Lukasz

    2010-03-23

    Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of approximately 27 amino acids that is not present in bacterial TSs. The extension, which is disordered in all reported crystal structures of TSs, has been considered to play a primary role in protein turnover but not in catalytic activity. In mammalian cells, the variant V3A has a half-life similar to that of wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have half-lives approximately half of that for wt hTS. Catalytic turnover rates for most Val3 mutants are only slightly diminished, as expected. However, two mutants, V3L and V3F, have strongly compromised dUMP binding, with K(m,app) values increased by factors of 47 and 58, respectively. For V3L, this observation can be explained by stabilization of the inactive conformation of the loop of residues 181-197, which prevents substrate binding. In the crystal structure of V3L, electron density corresponding to a leucine residue is present in a position that stabilizes the loop of residues 181-197 in the inactive conformation. Since this density is not observed in other mutants and all other leucine residues are ordered in this structure, it is likely that this density represents Leu3. In the crystal structure of a V3F.FdUMP binary complex, the nucleotide is bound in an alternative mode to that proposed for the catalytic complex, indicating that the high K(m,app) value is caused not by stabilization of the inactive conformer but by substrate binding in a nonproductive, inhibitory site. These observations show that the N-terminal extension affects the conformational state of the hTS catalytic region. Each of the mechanisms leading to the high K(m,app) values can be exploited to facilitate design of compounds acting as allosteric inhibitors of hTS.

  4. Safety Characteristics in System Application of Software for Human Rated Exploration Missions for the 8th IAASS Conference

    NASA Technical Reports Server (NTRS)

    Mango, Edward J.

    2016-01-01

    NASA and its industry and international partners are embarking on a bold and inspiring development effort to design and build an exploration class space system. The space system is made up of the Orion system, the Space Launch System (SLS) and the Ground Systems Development and Operations (GSDO) system. All are highly coupled together and dependent on each other for the combined safety of the space system. A key area of system safety focus needs to be in the ground and flight application software system (GFAS). In the development, certification and operations of GFAS, there are a series of safety characteristics that define the approach to ensure mission success. This paper will explore and examine the safety characteristics of the GFAS development. The GFAS system integrates the flight software packages of the Orion and SLS with the ground systems and launch countdown sequencers through the 'agile' software development process. A unique approach is needed to develop the GFAS project capabilities within this agile process. NASA has defined the software development process through a set of standards. The standards were written during the infancy of the so-called industry 'agile development' movement and must be tailored to adapt to the highly integrated environment of human exploration systems. Safety of the space systems and the eventual crew on board is paramount during the preparation of the exploration flight systems. A series of software safety characteristics have been incorporated into the development and certification efforts to ensure readiness for use and compatibility with the space systems. Three underlining factors in the exploration architecture require the GFAS system to be unique in its approach to ensure safety for the space systems, both the flight as well as the ground systems. The first are the missions themselves, which are exploration in nature, and go far beyond the comfort of low Earth orbit operations. The second is the current exploration

  5. C282Y-HFE Gene Variant Affects Cholesterol Metabolism in Human Neuroblastoma Cells

    PubMed Central

    Ali-Rahmani, Fatima; Huang, Michael A.; Schengrund, C.-L.; Connor, James R.; Lee, Sang Y.

    2014-01-01

    Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells. PMID:24533143

  6. Stress during pregnancy affects general intellectual and language functioning in human toddlers.

    PubMed

    Laplante, David P; Barr, Ronald G; Brunet, Alain; Galbaud du Fort, Guillaume; Meaney, Michael L; Saucier, Jean-Francois; Zelazo, Philip R; King, Suzanne

    2004-09-01

    Prenatal maternal stress has been shown to impair functioning in nonhuman primate offspring. Little is known about the effects of prenatal stress on intellectual and language development in humans because it is difficult to identify sufficiently large samples of pregnant women who have been exposed to an independent stressor. We took advantage of a natural disaster (January 1998 ice storm in Québec, Canada) to determine the effect of the objective severity of pregnant women's stress exposure on general intellectual and language development of their children. Bayley Mental Development Index (MDI) scores and parent-reported language abilities of 58 toddlers of mothers who were exposed to varying levels of prenatal stress were obtained at 2 y of age. The hierarchical multiple regression analyses indicated that the toddlers' birth weight and age at testing accounted for 12.0% and 14.8% of the variance in the Bayley MDI scores and in productive language abilities, respectively. More importantly, the level of prenatal stress exposure accounted for an additional 11.4% and 12.1% of the variance in the toddlers' Bayley MDI and productive language abilities and uniquely accounted for 17.3% of the variance of their receptive language abilities. The more severe the level of prenatal stress exposure, the poorer the toddlers' abilities. The level of prenatal stress exposure accounted for a significant proportion of the variance in the three dependent variables above and beyond that already accounted for by non-ice storm-related factors. We suspect that high levels of prenatal stress exposure, particularly early in the pregnancy, may negatively affect the brain development of the fetus, reflected in the lower general intellectual and language abilities in the toddlers.

  7. How Has Human-induced Climate Change Affected California Drought Risk?

    NASA Astrophysics Data System (ADS)

    Cheng, L.; Hoerling, M. P.; Aghakouchak, A.; Livneh, B.; Quan, X. W.; Eischeid, J. K.

    2015-12-01

    The current California drought has cast a heavy burden on statewide agriculture and water resources, further exacerbated by concurrent extreme high temperatures. Furthermore, industrial-era global radiative forcing brings into question the role of long-term climate change on CA drought. How has human-induced climate change affected California drought risk? Here, observations and model experimentation are applied to characterize this drought employing metrics that synthesize drought duration, cumulative precipitation deficit, and soil moisture depletion. The model simulations show that increases in radiative forcing since the late 19th Century induces both increased annual precipitation and increased surface temperature over California, consistent with prior model studies and with observed long-term change. As a result, there is no material difference in the frequency of droughts defined using bivariate indicators of precipitation and near-surface (10-cm) soil moisture, because shallow soil moisture responds most sensitively to increased evaporation driven by warming, which compensates the increase in the precipitation. However, when using soil moisture within a deep root zone layer (1-m) as co-variate, droughts become less frequent because deep soil moisture responds most sensitively to increased precipitation. The results illustrate the different land surface responses to anthropogenic forcing that are relevant for near-surface moisture exchange and for root zone moisture availability. The latter is especially relevant for agricultural impacts as the deep layer dictates moisture availability for plants, trees, and many crops. The results thus indicate the net effect of climate change has made agricultural drought less likely, and that the current severe impacts of drought on California's agriculture has not been substantially caused by long-term climate changes.

  8. Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion.

    PubMed

    Simann, Meike; Schneider, Verena; Le Blanc, Solange; Dotterweich, Julia; Zehe, Viola; Krug, Melanie; Jakob, Franz; Schilling, Tatjana; Schütze, Norbert

    2015-09-01

    Heparins are broadly used for the prevention and treatment of thrombosis and embolism. Yet, osteoporosis is considered to be a severe side effect in up to one third of all patients on long-term treatment. However, the mechanisms underlying this clinical problem are only partially understood. To investigate if heparin affects differentiation of skeletal precursors, we examined the effects of heparin on the osteogenic and adipogenic lineage commitment and differentiation of primary human bone marrow stromal cells (hBMSCs). Due to the known inverse relationship between adipogenesis and osteogenesis and the capacity of pre-differentiated cells to convert into the respective other lineage, we also determined heparin effects on osteogenic conversion and adipogenic differentiation/conversion. Interestingly, heparin did not only significantly increase mRNA expression and enzyme activity of the osteogenic marker alkaline phosphatase (ALP), but it also promoted mineralization during osteogenic differentiation and conversion. Furthermore, the mRNA expression of the osteogenic marker bone morphogenic protein 4 (BMP4) was enhanced. In addition, heparin administration partly prevented adipogenic differentiation and conversion demonstrated by reduced lipid droplet formation along with a decreased expression of adipogenic markers. Moreover, luciferase reporter assays, inhibitor experiments and gene expression analyses revealed that heparin had putative permissive effects on osteogenic signaling via the BMP pathway and reduced the mRNA expression of the Wnt pathway inhibitors dickkopf 1 (DKK1) and sclerostin (SOST). Taken together, our data show a rather supportive than inhibitory effect of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further studies will have to investigate the net effects of heparin administration on bone formation versus bone resorption in vivo to unravel the molecular mechanisms of heparin-associated osteoporosis and reconcile

  9. Safety issues of Lactobacillus bulgaricus with respect to human gelatinases in vitro.

    PubMed

    Stamatova, Iva; Meurman, Jukka H; Kari, Kirsti; Tervahartiala, Taina; Sorsa, Timo; Baltadjieva, Maria

    2007-10-01

    In oral medicine and dentistry probiotics have shown promising results in controlling dental diseases and yeast infections. This study was made to investigate the effect of eight strains of Lactobacillus bulgaricus and their effects on human matrix metalloproteinase-9 (MMP-9). The hypothesis was that these bacteria used in yoghurt production for centuries are not proteolytic and thus can be safely used in the development of probiotic preparations. Bacterial cell fractions and supernatant specimens were prepared and studied with gelatinase zymography and MMP-9 activation was assessed by immunoblotting. The effect of synthetic MMP inhibitors and a serine protease inhibitor (Pefabloc) on bacterial proteinases was studied with zymography. The results showed very low gelatinolytic activity. There was a slight difference between the supernatant and cell fractions so that the supernatant specimens produced weak gelatinolytic bands in zymography while hardly anything was seen in the cell fraction series. The tested synthetic MMP inhibitors and Pefabloc did not affect the proteolytic activity of the lactobacilli strains. The lactobacilli did not seem to induce the conversion of proMMP-9 to its active form. Consequently, our study hypothesis was confirmed and the studied Lactobacillus strains are not likely to degrade host tissue components.

  10. Fire safety applications for spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Olson, Sandra L.

    1989-01-01

    Fire safety for spacecraft is reviewed by first describing current practices, many of which are adapted directly from aircraft. Then, current analyses and experimental knowledge in low-gravity combustion, with implications for fire safety are discussed. In orbiting spacecraft, the detection and suppression of flames are strongly affected by the large reduction in buoyant flows under low gravity. Generally, combustion intensity is reduced in low gravity. There are some notable exceptions, however, one example being the strong enhancement of flames by low-velocity ventilation flows in space. Finally, the future requirements in fire safety, particularly the needs of long-duration space stations in fire prevention, detection, extinguishment, and atmospheric control are examined. The goal of spacecraft fire-safety investigations is the establishment of trade-offs that promote maximum safety without hampering the useful human and scientific activities in space.

  11. Using the WTO/TBT enquiry point to monitor tendencies in the regulation of environment, health, and safety issues affecting the chemical industry.

    PubMed

    Pio Borges Menezes, Rodrigo; Maria de Souza Antunes, Adelaide

    2005-04-01

    The growing importance of technical regulation affecting the use and sale of chemical products is a topic of interest not only for the chemical industry, but also for governments, nongovernmental organizations, consumers, and interested communities. The results of such regulation on behalf of the environment, health and safety of individuals, as well as its economic effects on industrial activity, are well understood in the United States and recently in the European Union. In less developed countries, however, the general level of public understanding of these issues is still minimal. It is common knowledge that the so-called "regulatory asymmetry" between countries at different levels of development contributes to the establishment of technical barriers to trade. Such asymmetries, however, also have other impacts: the displacement of polluting industrial sectors to countries which have less demanding regulations, the concentration of unsafe and harmful environmental conditions in certain parts of the globe, and the competitive disadvantage for industries located in countries where control is more rigid. This study analyses information on a wide range of technical regulations issued by World Trade Organization (WTO) members, and focuses on those regulations that affect the chemical industry. This information is available through the WTO Enquiry Points, organizations created in each country to administrate the Technical Barriers to Trade Agreement (TBT). This article consists of an analysis of 4,301 notifications of technical regulations by WTO member states in the 7-year period following the establishment of the WTO in 1995. Starting from this mass of information, 585 notifications that affect the circulation or use of chemical products were isolated. Of this group, 71% refer to only 15 countries. This group of notifications was further classified according to their motivation (the environment, health, safety), by the type of product affected (medications, fuels

  12. Trends Affecting Ohio State University Extension in the 21st Century and the Implications for Human Capital

    ERIC Educational Resources Information Center

    Cochran, Graham R.; Ferrari, Theresa M.; Chen, Claire Yueh-Ti

    2012-01-01

    Research with a diverse array of organizations in the public and private sectors has documented a common set of trends affecting organizations and their human capital in the 21st century. Similar trends have been identified as important for Extension organizations and the Cooperative Extension System. It is important to determine if such trends…

  13. Safety Psychology Applicating on Coal Mine Safety Management Based on Information System

    NASA Astrophysics Data System (ADS)

    Hou, Baoyue; Chen, Fei

    In recent years, with the increase of intensity of coal mining, a great number of major accidents happen frequently, the reason mostly due to human factors, but human's unsafely behavior are affected by insecurity mental control. In order to reduce accidents, and to improve safety management, with the help of application security psychology, we analyse the cause of insecurity psychological factors from human perception, from personality development, from motivation incentive, from reward and punishment mechanism, and from security aspects of mental training , and put forward countermeasures to promote coal mine safety production,and to provide information for coal mining to improve the level of safety management.

  14. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    SciTech Connect

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  15. Probiotic screening and safety evaluation of Lactobacillus strains from plants, artisanal goat cheese, human stools, and breast milk.

    PubMed

    Gotteland, Martin; Cires, Maria Jose; Carvallo, Claudia; Vega, Natalia; Ramirez, Maria Antonieta; Morales, Pamela; Rivas, Patricia; Astudillo, Fernanda; Navarrete, Paola; Dubos, Céline; Figueroa, Alvaro; Troncoso, Miriam; Ulloa, Carolina; Mizgier, Maria Luisa; Carrasco-Pozo, Catalina; Speisky, Hernan; Brunser, Oscar; Figueroa, Guillermo

    2014-04-01

    The aim of this study was to select autochthonous strains of Lactobacillus from stools of healthy infants and adults, human milk, artisanal goat cheese, and fruits and vegetables according to their probiotic properties and safety. From 421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to gastric pH and bile salts; they were used to determine their anti-Helicobacter pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity), and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis factor-α-stimulated HT-29 cells) activities as well as their ability to adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results obtained were compared with three commercial probiotic Lactobacillus rhamnosus GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient according to these activities were subsequently identified by sequencing their 16S rRNA gene, their susceptibility to antibiotics was determined, and their safety evaluated in mice. One strain of L. plantarum was discarded due to the higher prevalence of liver bacterial translocation observed in the animals fed this strain. In conclusion, four autochthonous strains of L. rhamnosus were finally selected with probiotic properties and safety allowing their eventual use in human studies. These results contribute to increase the diversity of probiotic strains available for the development of nutraceuticals and functional foods.

  16. The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives

    PubMed Central

    Ottaviani, Javier I.; Borges, Gina; Momma, Tony Y.; Spencer, Jeremy P. E.; Keen, Carl L.; Crozier, Alan; Schroeter, Hagen

    2016-01-01

    Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (−)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-14C](−)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations. PMID:27363516

  17. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives.

    PubMed

    Ottaviani, Javier I; Borges, Gina; Momma, Tony Y; Spencer, Jeremy P E; Keen, Carl L; Crozier, Alan; Schroeter, Hagen

    2016-07-01

    Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations.

  18. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study.

    PubMed

    Burton, J P; Cowley, S; Simon, R R; McKinney, J; Wescombe, P A; Tagg, J R

    2011-09-01

    Streptococcus salivarius is naturally a predominant member of the human oropharynx and the commercial probiotic strain K12 has been consumed for more than a decade. The present study examines the health responses of human volunteers to oral ingestion of high doses of S. salivarius K12. A randomized group of 53 subjects received a dose of 1 × 10(10)cfu S. salivarius K12 (N=25) or placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine and saliva samples were collected at baseline and following treatment and analyzed, while the oral and gastrointestinal tolerance of the subjects to the dosing regimen was determined by use of questionnaires. Adverse events (AE)s were recorded for both groups. No statistically significant differences between the probiotic and placebo treated groups were detected in either the blood clinical chemistry or hematology results (P>0.05). The questionnaire responses of the subjects indicated that both treatments were well tolerated. The frequency and intensity of AEs was similar in the two groups. This data demonstrates that the daily ingestion of S. salivarius K12 over a 28-day period does not adversely affect the human host and supports the safety of its oral delivery in a food-based carrier. PMID:21722694

  19. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives.

    PubMed

    Ottaviani, Javier I; Borges, Gina; Momma, Tony Y; Spencer, Jeremy P E; Keen, Carl L; Crozier, Alan; Schroeter, Hagen

    2016-01-01

    Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations. PMID:27363516

  20. LD-Aminopterin in the Canine Homologue of Human Atopic Dermatitis: A Randomized, Controlled Trial Reveals Dosing Factors Affecting Optimal Therapy

    PubMed Central

    Zebala, John A.; Mundell, Alan; Messinger, Linda; Griffin, Craig E.; Schuler, Aaron D.; Kahn, Stuart J.

    2014-01-01

    Background Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. Methods and Findings This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Conclusions Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD. PMID:25255447

  1. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy.

    PubMed

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara; Desoye, Gernot; Hansson, Stefan; Kenna, Gerry; Knudsen, Lisbeth E; Markert, Udo R; Powles-Glover, Nicola; Schneider, Henning; Leach, Lopa

    2016-09-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.

  2. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy.

    PubMed

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara; Desoye, Gernot; Hansson, Stefan; Kenna, Gerry; Knudsen, Lisbeth E; Markert, Udo R; Powles-Glover, Nicola; Schneider, Henning; Leach, Lopa

    2016-09-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice. PMID:27327413

  3. Woodland Patch Dynamics Affected by Oak Growth: Fire, Climate, and Human Influences

    NASA Astrophysics Data System (ADS)

    Murray, D. B.; White, J. D.

    2010-12-01

    Woodland fragmentation and aggregation occur due to impacts of fire, climate, and human factors. In our study we investigate the growth response of a deciduous oak species, Quercus buckleyii (Texas Red Oak) within a juniper-dominated woodland. This species may be a sentinel species for woodland patch developmental processes that could be used as a proxy for woodland patch contraction and expansion events. In this study, we used tree rings, fire scar, and multi-temporal aerial photographic data to assess response of oaks to disturbance type and resultant impact on woodland patches. Three hundred and seventy tree slabs from downed and dead red oaks were collected in the Balcones National Wildlife Refuge outside Austin, Texas. We analyzed tree rings from these slabs to determine recruitment date, annual ring width, and where evident, time of fire. Changes in tree ring widths associated with canopy openings were derived from neighborhood analysis of digital aerial photos from 1939, 1951, 1964, 1980, 1995, and 2004. Results indicated that red oaks increased radial growth following fire. Analysis of canopy openings associated with the aerial photographs showed that the oak species did not respond to canopy openings with increased radial growth as predicted by gap-phase dynamics. Climate impacted average radial ring growth as demonstrated by comparison with the Palmer Drought Severity and Nino 3 Index values (p = .56). Given that radial growth is influenced by both fire and climate, we explored the possibility that dramatic climate and related disturbance events (drought and high occurrence of fire) of the 1950’s created a possible ecological regime shift. Changes in both index value variance and disturbance frequency were noted during the 1950’s. These results were confirmed by landscape analysis of disturbance patches identified from the historical photographs which show cutting and burning occurred with the highest frequency between 1951 and 1964 with 70% of the

  4. Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools

    ERIC Educational Resources Information Center

    Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

    2011-01-01

    Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

  5. Connecting art and science: An interdisciplinary strategy and its impact on the affective domain of community college human anatomy students

    NASA Astrophysics Data System (ADS)

    Petti, Kevin

    Educational objectives are often described within the framework of a three-domain taxonomy: cognitive, affective and psychomotor. While most of the research on educational objectives has focused on the cognitive domain, the research that has been conducted on the affective domain, which speaks to emotions, attitudes, and values, has identified a number of positive outcomes. One approach to enhancing the affective domain is that of interdisciplinary education. Science education research in the realm of interdisciplinary education and affective outcomes is limited; especially research conducted on community college students of human anatomy. This project investigated the relationship between an interdisciplinary teaching strategy and the affective domain in science education by utilizing an interdisciplinary lecture in a human anatomy class. Subjects were anatomy students in a California community college who listened to a one-hour lecture describing the cultural, historical and scientific significance of selected pieces of art depicting human dissection in European medieval and Renaissance universities. The focus was on how these renderings represent the state of anatomy education during their respective eras. After listening to the lecture, subjects were administered a 35-question survey that was composed of 14 demographic questions and 21 Likert-style statements that asked respondents to rate the extent to which the intervention influenced their affective domain. Descriptive statistics were then used to determine which component of the affective domain was most influenced, and multiple regression analysis was used to examine the extent to which individual differences along the affective continuum were explained by select demographic measures such as gender, race/ethnicity, education level, and previous exposure to science courses. Results indicate that the interdisciplinary intervention had a positive impact on every component of the affective domain hierarchy

  6. Human ergology that promotes participatory approach to improving safety, health and working conditions at grassroots workplaces: achievements and actions.

    PubMed

    Kawakami, Tsuyoshi

    2011-12-01

    Participatory approaches are increasingly applied to improve safety, health and working conditions of grassroots workplaces in Asia. The core concepts and methods in human ergology research such as promoting real work life studies, relying on positive efforts of local people (daily life-technology), promoting active participation of local people to identify practical solutions, and learning from local human networks to reach grassroots workplaces, have provided useful viewpoints to devise such participatory training programmes. This study was aimed to study and analyze how human ergology approaches were applied in the actual development and application of three typical participatory training programmes: WISH (Work Improvement for Safe Home) with home workers in Cambodia, WISCON (Work Improvement in Small Construction Sites) with construction workers in Thailand, and WARM (Work Adjustment for Recycling and Managing Waste) with waste collectors in Fiji. The results revealed that all the three programmes, in the course of their developments, commonly applied direct observation methods of the work of target workers before devising the training programmes, learned from existing local good examples and efforts, and emphasized local human networks for cooperation. These methods and approaches were repeatedly applied in grassroots workplaces by taking advantage of their the sustainability and impacts. It was concluded that human ergology approaches largely contributed to the developments and expansion of participatory training programmes and could continue to support the self-help initiatives of local people for promoting human-centred work.

  7. Human ergology that promotes participatory approach to improving safety, health and working conditions at grassroots workplaces: achievements and actions.

    PubMed

    Kawakami, Tsuyoshi

    2011-12-01

    Participatory approaches are increasingly applied to improve safety, health and working conditions of grassroots workplaces in Asia. The core concepts and methods in human ergology research such as promoting real work life studies, relying on positive efforts of local people (daily life-technology), promoting active participation of local people to identify practical solutions, and learning from local human networks to reach grassroots workplaces, have provided useful viewpoints to devise such participatory training programmes. This study was aimed to study and analyze how human ergology approaches were applied in the actual development and application of three typical participatory training programmes: WISH (Work Improvement for Safe Home) with home workers in Cambodia, WISCON (Work Improvement in Small Construction Sites) with construction workers in Thailand, and WARM (Work Adjustment for Recycling and Managing Waste) with waste collectors in Fiji. The results revealed that all the three programmes, in the course of their developments, commonly applied direct observation methods of the work of target workers before devising the training programmes, learned from existing local good examples and efforts, and emphasized local human networks for cooperation. These methods and approaches were repeatedly applied in grassroots workplaces by taking advantage of their the sustainability and impacts. It was concluded that human ergology approaches largely contributed to the developments and expansion of participatory training programmes and could continue to support the self-help initiatives of local people for promoting human-centred work. PMID:25665213

  8. Haloperidol, but not olanzapine, may affect expression of PER1 and CRY1 genes in human glioblastoma cell line

    PubMed Central

    Mokros, Łukasz; Karbownik, Michał Seweryn; Nowakowska-Domagała, Katarzyna; Szemraj, Janusz; Wieteska, Łukasz; Woźniak, Karol; Witusik, Andrzej; Antczak, Adam; Pietras, Tadeusz

    2016-01-01

    Abstract Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h. Real-time quantitative polymerase chain reaction with the ΔC T analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 μM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 μM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect was observed. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive.

  9. Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2'-O-Fucosyllactose (2'FL).

    PubMed

    Coulet, Myriam; Phothirath, Phoukham; Allais, Linda; Schilter, Benoit

    2014-02-01

    In order to match the composition of human breast milk more closely, it is now possible to supplement commercial infant formula (IF) with synthesised oligosaccharides that are chemically identical to human milk oligosaccharides. The safety data generated on a new human-identical milk oligosaccharide (HiMO), 2'-O-Fucosyllactose (2'FL), are presented. Standard in vitro genotoxicity tests were performed. To investigate the toxicological profile in a model representative of the intended target population, 2'FL was administered via gavage in a juvenile adapted sub-chronic rat study at dose levels of 0, 2000, 5000 and 6000 mg/kgbw/day. Fructooligosaccharide (FOS), currently acknowledged as safe and approved for use in IF, was used as a reference high-dose control at 6000 mg/kgbw/day. 2'FL was non-mutagenic in the in vitro assays. Oral administration up to 5000 mg/kgbw/day to rats over 90 days was not associated with any adverse effects based on clinical observations, body weight gain, food consumption, ophthalmoscopy, clinical pathology, organ weights and histopathology findings. Based on this 90-day study, a No Observed Adverse Effect Level (NOAEL) of 5000 mg/kgbw/day for both male and female rats was established for 2'FL. These findings support the safety of synthetic 2'FL for possible use in infant food. PMID:24262411

  10. Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2'-O-Fucosyllactose (2'FL).

    PubMed

    Coulet, Myriam; Phothirath, Phoukham; Allais, Linda; Schilter, Benoit

    2014-02-01

    In order to match the composition of human breast milk more closely, it is now possible to supplement commercial infant formula (IF) with synthesised oligosaccharides that are chemically identical to human milk oligosaccharides. The safety data generated on a new human-identical milk oligosaccharide (HiMO), 2'-O-Fucosyllactose (2'FL), are presented. Standard in vitro genotoxicity tests were performed. To investigate the toxicological profile in a model representative of the intended target population, 2'FL was administered via gavage in a juvenile adapted sub-chronic rat study at dose levels of 0, 2000, 5000 and 6000 mg/kgbw/day. Fructooligosaccharide (FOS), currently acknowledged as safe and approved for use in IF, was used as a reference high-dose control at 6000 mg/kgbw/day. 2'FL was non-mutagenic in the in vitro assays. Oral administration up to 5000 mg/kgbw/day to rats over 90 days was not associated with any adverse effects based on clinical observations, body weight gain, food consumption, ophthalmoscopy, clinical pathology, organ weights and histopathology findings. Based on this 90-day study, a No Observed Adverse Effect Level (NOAEL) of 5000 mg/kgbw/day for both male and female rats was established for 2'FL. These findings support the safety of synthetic 2'FL for possible use in infant food.

  11. Human factors with nonhumans - Factors that affect computer-task performance

    NASA Technical Reports Server (NTRS)

    Washburn, David A.

    1992-01-01

    There are two general strategies that may be employed for 'doing human factors research with nonhuman animals'. First, one may use the methods of traditional human factors investigations to examine the nonhuman animal-to-machine interface. Alternatively, one might use performance by nonhuman animals as a surrogate for or model of performance by a human operator. Each of these approaches is illustrated with data in the present review. Chronic ambient noise was found to have a significant but inconsequential effect on computer-task performance by rhesus monkeys (Macaca mulatta). Additional data supported the generality of findings such as these to humans, showing that rhesus monkeys are appropriate models of human psychomotor performance. It is argued that ultimately the interface between comparative psychology and technology will depend on the coordinated use of both strategies of investigation.

  12. Human health safety evaluation of cosmetics in the EU: A legally imposed challenge to science

    SciTech Connect

    Pauwels, M.; Rogiers, V.

    2010-03-01

    As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients. This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.

  13. Human health safety evaluation of cosmetics in the EU: a legally imposed challenge to science.

    PubMed

    Pauwels, M; Rogiers, V

    2010-03-01

    As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients. This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.

  14. Oxygen safety

    MedlinePlus

    COPD - oxygen safety; Chronic obstructive pulmonary disease - oxygen safety; Chronic obstructive airways disease - oxygen safety; Emphysema - oxygen safety; Heart failure - oxygen-safety; Palliative care - oxygen safety; ...

  15. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans.

    PubMed

    Coenen, Volker A; Schlaepfer, Thomas E; Maedler, Burkhard; Panksepp, Jaak

    2011-10-01

    Major depression (MD) might be conceptualized as pathological under-arousal of positive affective systems as parts of a network of brain regions assessing, reconciling and storing emotional stimuli versus an over-arousal of parts of the same network promoting separation-distress/GRIEF. In this context depression can be explained as an emotional pain state that is the result of a disregulation of several sub-systems that under physiological conditions are concerned with bodily or emotional homeostasis of the human organism in a social context. Physiologically, homeostasis is maintained by influences of the SEEKING system represented - amongst others - by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects in humans suffering from MD by re-initiating an emotional equilibrium (of higher or lower activity) between these opposing systems. PMID:21184778

  16. Personalized medicine in human space flight: using Omics based analyses to develop individualized countermeasures that enhance astronaut safety and performance.

    PubMed

    Schmidt, Michael A; Goodwin, Thomas J

    2013-01-01

    Space flight is one of the most extreme conditions encountered by humans. Advances in Omics methodologies (genomics, transcriptomics, proteomics, and metabolomics) have revealed that unique differences exist between individuals. These differences can be amplified in extreme conditions, such as space flight. A better understanding of individual differences may allow us to develop personalized countermeasure packages that optimize the safety and performance of each astronaut. In this review, we explore the role of "Omics" in advancing our ability to: (1) more thoroughly describe the biological response of humans in space; (2) describe molecular attributes of individual astronauts that alter the risk profile prior to entering the space environment; (3) deploy Omics techniques in the development of personalized countermeasures; and (4) develop a comprehensive Omics-based assessment and countermeasure platform that will guide human space flight in the future. In this review, we advance the concept of personalized medicine in human space flight, with the goal of enhancing astronaut safety and performance. Because the field is vast, we explore selected examples where biochemical individuality might significantly impact countermeasure development. These include gene and small molecule variants associated with: (1) metabolism of therapeutic drugs used in space; (2) one carbon metabolism and DNA stability; (3) iron metabolism, oxidative stress and damage, and DNA stability; and (4) essential input (Mg and Zn) effects on DNA repair. From these examples, we advance the case that widespread Omics profiling should serve as the foundation for aerospace medicine and research, explore methodological considerations to advance the field, and suggest why personalized medicine may become the standard of care for humans in space.

  17. First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090)

    PubMed Central

    Fuchs, Jonathan D.; Frank, Ian; Elizaga, Marnie L.; Allen, Mary; Frahm, Nicole; Kochar, Nidhi; Li, Sue; Edupuganti, Srilatha; Kalams, Spyros A.; Tomaras, Georgia D.; Sheets, Rebecca; Pensiero, Michael; Tremblay, Marc A.; Higgins, Terry J.; Latham, Theresa; Egan, Michael A.; Clarke, David K.; Eldridge, John H.

    2015-01-01

    Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 103 to 3.4 × 107 particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases. PMID:26199949

  18. Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

    SciTech Connect

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

    2003-02-24

    As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

  19. Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays.

    PubMed

    Harris, Kate; Aylott, Mike; Cui, Yi; Louttit, James B; McMahon, Nicholas C; Sridhar, Arun

    2013-08-01

    Human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are a potential source to develop assays for predictive electrophysiological safety screening. Published studies show that the relevant physiology and pharmacology exist but does not show the translation between stem cell cardiomyocyte assays and other preclinical safety screening assays, which is crucial for drug discovery and safety scientists and the regulators. Our studies are the first to show the pharmacology of ion channel blockade and compare them with existing functional cardiac electrophysiology studies. Ten compounds (a mixture of pure hERG [E-4031 and Cisapride], hERG and sodium [Flecainide, Mexiletine, Quinidine, and Terfenadine], calcium channel blockers [Nifedipine and Verapamil], and two proprietary compounds [GSK A and B]) were tested, and results from hiPSC-CMs studied on multielectrode arrays (MEA) were compared with other preclincial models and clinical drug concentrations and effects using integrated risk assessment plots. All ion channel blockers produced (1) functional effects on repolarization and depolarization around the IC25 and IC50 values and (2) excessive blockade of hERG and/or blockade of sodium current precipitated arrhythmias. Our MEA data show that hiPSC-CMs demonstrate relevant pharmacology and show excellent correlations to current functional cardiac electrophysiological studies. Based on these results, MEA assays using iPSC-CMs offer a reliable, cost effective, and surrogate to preclinical in vitro testing, in addition to the 3Rs (refine, reduce, and replace animals in research) benefit. PMID:23690542

  20. Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia

    PubMed Central

    van den Boogaard, Florry E.; Hofstra, Jorrit J.; van ‘t Veer, Cornelis; Levi, Marcel M.; Roelofs, Joris J. T. H.; van der Poll, Tom; Schultz, Marcus J.

    2015-01-01

    Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia. Anticoagulant strategies could benefit patients with pneumonia, but systemic administration of anticoagulant agents may lead to suboptimal local levels and may cause systemic hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human tissue factor pathway inhibitor (rh-TFPI) in a well-established rat model of Streptococcus (S.) pneumoniae pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S. pneumonia causing pneumonia, rats were subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42 hours. Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and systemic TFPI activity and systemic coagulation were not affected. Histopathology revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems feasible and safe; local anticoagulant treatment with rh-TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae pneumonia. PMID:25992779

  1. Surveying Wearable Human Assistive Technology for Life and Safety Critical Applications: Standards, Challenges and Opportunities

    PubMed Central

    Alam, Muhammad Mahtab; Ben Hamida, Elyes

    2014-01-01

    In this survey a new application paradigm life and safety for critical operations and missions using wearable Wireless Body Area Networks (WBANs) technology is introduced. This paradigm has a vast scope of applications, including disaster management, worker safety in harsh environments such as roadside and building workers, mobile health monitoring, ambient assisted living and many more. It is often the case that during the critical operations and the target conditions, the existing infrastructure is either absent, damaged or overcrowded. In this context, it is envisioned that WBANs will enable the quick deployment of ad-hoc/on-the-fly communication networks to help save many lives and ensuring people's safety. However, to understand the applications more deeply and their specific characteristics and requirements, this survey presents a comprehensive study on the applications scenarios, their context and specific requirements. It explores details of the key enabling standards, existing state-of-the-art research studies, and projects to understand their limitations before realizing aforementioned applications. Application-specific challenges and issues are discussed comprehensively from various perspectives and future research and development directions are highlighted as an inspiration for new innovative solutions. To conclude, this survey opens up a good opportunity for companies and research centers to investigate old but still new problems, in the realm of wearable technologies, which are increasingly evolving and getting more and more attention recently. PMID:24859024

  2. Surveying wearable human assistive technology for life and safety critical applications: standards, challenges and opportunities.

    PubMed

    Alam, Muhammad Mahtab; Ben Hamida, Elyes

    2014-05-23

    In this survey a new application paradigm life and safety for critical operations and missions using wearable Wireless Body Area Networks (WBANs) technology is introduced. This paradigm has a vast scope of applications, including disaster management, worker safety in harsh environments such as roadside and building workers, mobile health monitoring, ambient assisted living and many more. It is often the case that during the critical operations and the target conditions, the existing infrastructure is either absent, damaged or overcrowded. In this context, it is envisioned that WBANs will enable the quick deployment of ad-hoc/on-the-fly communication networks to help save many lives and ensuring people's safety. However, to understand the applications more deeply and their specific characteristics and requirements, this survey presents a comprehensive study on the applications scenarios, their context and specific requirements. It explores details of the key enabling standards, existing state-of-the-art research studies, and projects to understand their limitations before realizing aforementioned applications. Application-specific challenges and issues are discussed comprehensively from various perspectives and future research and development directions are highlighted as an inspiration for new innovative solutions. To conclude, this survey opens up a good opportunity for companies and research centers to investigate old but still new problems, in the realm of wearable technologies, which are increasingly evolving and getting more and more attention recently.

  3. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates✩

    PubMed Central

    Lukashevich, Igor S.; Carrion, Ricardo; Salvato, Maria S.; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E.; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

    2008-01-01

    A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever. PMID:18692539

  4. Development and Validation of the Total HUman Model for Safety (THUMS) Version 5 Containing Multiple 1D Muscles for Estimating Occupant Motions with Muscle Activation During Side Impacts.

    PubMed

    Iwamoto, Masami; Nakahira, Yuko

    2015-11-01

    Accurate prediction of occupant head kinematics is critical for better understanding of head/face injury mechanisms in side impacts, especially far-side occupants. In light of the fact that researchers have demonstrated that muscle activations, especially in neck muscles, can affect occupant head kinematics, a human body finite element (FE) model that considers muscle activation is useful for predicting occupant head kinematics in real-world automotive accidents. In this study, we developed a human body FE model called the THUMS (Total HUman Model for Safety) Version 5 that contains 262 one-dimensional (1D) Hill-type muscle models over the entire body. The THUMS was validated against 36 series of PMHS (Post Mortem Human Surrogate) and volunteer test data in this study, and 16 series of PMHS and volunteer test data on side impacts are presented. Validation results with force-time curves were also evaluated quantitatively using the CORA (CORrelation and Analysis) method. The validation results suggest that the THUMS has good biofidelity in the responses of the regional or full body for side impacts, but relatively poor biofidelity in its local level of responses such as brain displacements. Occupant kinematics predicted by the THUMS with a muscle controller using 22 PID (Proportional-Integral- Derivative) controllers were compared with those of volunteer test data on low-speed lateral impacts. The THUMS with muscle controller reproduced the head kinematics of the volunteer data more accurately than that without muscle activation, although further studies on validation of torso kinematics are needed for more accurate predictions of occupant head kinematics.

  5. Development and Validation of the Total HUman Model for Safety (THUMS) Version 5 Containing Multiple 1D Muscles for Estimating Occupant Motions with Muscle Activation During Side Impacts.

    PubMed

    Iwamoto, Masami; Nakahira, Yuko

    2015-11-01

    Accurate prediction of occupant head kinematics is critical for better understanding of head/face injury mechanisms in side impacts, especially far-side occupants. In light of the fact that researchers have demonstrated that muscle activations, especially in neck muscles, can affect occupant head kinematics, a human body finite element (FE) model that considers muscle activation is useful for predicting occupant head kinematics in real-world automotive accidents. In this study, we developed a human body FE model called the THUMS (Total HUman Model for Safety) Version 5 that contains 262 one-dimensional (1D) Hill-type muscle models over the entire body. The THUMS was validated against 36 series of PMHS (Post Mortem Human Surrogate) and volunteer test data in this study, and 16 series of PMHS and volunteer test data on side impacts are presented. Validation results with force-time curves were also evaluated quantitatively using the CORA (CORrelation and Analysis) method. The validation results suggest that the THUMS has good biofidelity in the responses of the regional or full body for side impacts, but relatively poor biofidelity in its local level of responses such as brain displacements. Occupant kinematics predicted by the THUMS with a muscle controller using 22 PID (Proportional-Integral- Derivative) controllers were compared with those of volunteer test data on low-speed lateral impacts. The THUMS with muscle controller reproduced the head kinematics of the volunteer data more accurately than that without muscle activation, although further studies on validation of torso kinematics are needed for more accurate predictions of occupant head kinematics. PMID:26660740

  6. Hand Safety

    MedlinePlus

    ... en gatillo See More... Hand Anatomy Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening ... en gatillo See More... Hand Anatomy Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening ...

  7. Hand Safety

    MedlinePlus

    ... Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening Safety Turkey Carving Removing a Ring Español Artritis ... Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening Safety Turkey Carving Removing a Ring Español Artritis ...

  8. Human Impacts Affect Tree Community Features of 20 Forest Fragments of a Vanishing Neotropical Hotspot

    NASA Astrophysics Data System (ADS)

    Pereira, José Aldo Alves; de Oliveira-Filho, Ary Teixeira; Eisenlohr, Pedro V.; Miranda, Pedro L. S.; de Lemos Filho, José Pires

    2015-02-01

    The loss in forest area due to human occupancy is not the only threat to the remaining biodiversity: forest fragments are susceptible to additional human impact. Our aim was to investigate the effect of human impact on tree community features (species composition and abundance, and structural descriptors) and check if there was a decrease in the number of slender trees, an increase in the amount of large trees, and also a reduction in the number of tree species that occur in 20 fragments of Atlantic montane semideciduous forest in southeastern Brazil. We produced digital maps of each forest fragment using Landsat 7 satellite images and processed the maps to obtain morphometric variables. We used investigative questionnaires and field observations to survey the history of human impact. We then converted the information into scores given to the extent, severity, and duration of each impact, including proportional border area, fire, trails, coppicing, logging, and cattle, and converted these scores into categorical levels. We used linear models to assess the effect of impacts on tree species abundance distribution and stand structural descriptors. Part of the variation in floristic patterns was significantly correlated to the impacts of fire, logging, and proportional border area. Structural descriptors were influenced by cattle and outer roads. Our results provided, for the first time, strong evidence that tree species occurrence and abundance, and forest structure of Atlantic seasonal forest fragments respond differently to various modes of disturbance by humans.

  9. Human impacts affect tree community features of 20 forest fragments of a vanishing neotropical hotspot.

    PubMed

    Pereira, José Aldo Alves; de Oliveira-Filho, Ary Teixeira; Eisenlohr, Pedro V; Miranda, Pedro L S; de Lemos Filho, José Pires

    2015-02-01

    The loss in forest area due to human occupancy is not the only threat to the remaining biodiversity: forest fragments are susceptible to additional human impact. Our aim was to investigate the effect of human impact on tree community features (species composition and abundance, and structural descriptors) and check if there was a decrease in the number of slender trees, an increase in the amount of large trees, and also a reduction in the number of tree species that occur in 20 fragments of Atlantic montane semideciduous forest in southeastern Brazil. We produced digital maps of each forest fragment using Landsat 7 satellite images and processed the maps to obtain morphometric variables. We used investigative questionnaires and field observations to survey the history of human impact. We then converted the information into scores given to the extent, severity, and duration of each impact, including proportional border area, fire, trails, coppicing, logging, and cattle, and converted these scores into categorical levels. We used linear models to assess the effect of impacts on tree species abundance distribution and stand structural descriptors. Part of the variation in floristic patterns was significantly correlated to the impacts of fire, logging, and proportional border area. Structural descriptors were influenced by cattle and outer roads. Our results provided, for the first time, strong evidence that tree species occurrence and abundance, and forest structure of Atlantic seasonal forest fragments respond differently to various modes of disturbance by humans.

  10. Human impacts affect tree community features of 20 forest fragments of a vanishing neotropical hotspot.

    PubMed

    Pereira, José Aldo Alves; de Oliveira-Filho, Ary Teixeira; Eisenlohr, Pedro V; Miranda, Pedro L S; de Lemos Filho, José Pires

    2015-02-01

    The loss in forest area due to human occupancy is not the only threat to the remaining biodiversity: forest fragments are susceptible to additional human impact. Our aim was to investigate the effect of human impact on tree community features (species composition and abundance, and structural descriptors) and check if there was a decrease in the number of slender trees, an increase in the amount of large trees, and also a reduction in the number of tree species that occur in 20 fragments of Atlantic montane semideciduous forest in southeastern Brazil. We produced digital maps of each forest fragment using Landsat 7 satellite images and processed the maps to obtain morphometric variables. We used investigative questionnaires and field observations to survey the history of human impact. We then converted the information into scores given to the extent, severity, and duration of each impact, including proportional border area, fire, trails, coppicing, logging, and cattle, and converted these scores into categorical levels. We used linear models to assess the effect of impacts on tree species abundance distribution and stand structural descriptors. Part of the variation in floristic patterns was significantly correlated to the impacts of fire, logging, and proportional border area. Structural descriptors were influenced by cattle and outer roads. Our results provided, for the first time, strong evidence that tree species occurrence and abundance, and forest structure of Atlantic seasonal forest fragments respond differently to various modes of disturbance by humans. PMID:25344658

  11. Human erythrocytes are affected in vitro by flavonoids of Aristotelia chilensis (Maqui) leaves.

    PubMed

    Suwalsky, Mario; Vargas, Pedro; Avello, Marcia; Villena, Fernando; Sotomayor, Carlos P

    2008-11-01

    Aristotelia chilensis (Mol.) Stuntz (A. chilensis), also known as maqui, is a plant of the Elaeocarpaceae family that grows in central and southern Chile as well as southwestern Argentina. Infusions of its leaves have long been used in the traditional native herbal medicine to treat different ailments. Phytochemical studies of the plant's chemical composition of the plant indicate the presence of indolic alkaloids, flavonoids, cianidine glucosides, delfidine, malvidine, petunidine, cumarines and triterpenes. These compounds, particularly the flavonoids, have antioxidant properties. In order to evaluate the mechanisms of its toxicity and their antioxidant properties, the leaves' aqueous extracts were induced to interact with human red cells, their isolated unsealed membranes (IUM), and molecular models of the human erythrocyte membrane. These consisted of multibilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, and large unilamellar vesicles (LUV) of DMPC. The capacity of A. chilensis aqueous extracts to perturb the bilayer structure of DMPC and DMPE was evaluated by X-ray diffraction, DMPC LUV and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). Results of the present study indicate that aqueous extracts of A. chilensis induced an alteration of human erythrocyte morphology from the normal discoid shape to an echinocytic form, changes that are explained in terms of the extract interaction with the membrane's outer phospholipid monolayer. PMID:18687390

  12. Human systemic exposure to [¹⁴C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment.

    PubMed

    Nohynek, Gerhard J; Skare, Julie A; Meuling, Wim J A; Wehmeyer, Kenneth R; de Bie, Albertus Th H J; Vaes, Wouter H J; Dufour, Eric K; Fautz, Rolf; Steiling, Winfried; Bramante, Mario; Toutain, Herve

    2015-07-01

    Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [(14)C] was measured in all materials, rinsing water, hair, plasma, urine and skin strips. Plasma and urine were also analysed by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or 97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-∞) values 1415 or 966 ng [(14)C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly occurred within 24 hrs after hair colouring with a total excretion of 0.72 or 0.88% of applied radioactivity in studies A or B, respectively. Only N,N'-diacetylated-PPD was detected in plasma and the urine. A TK-based human safety assessment estimated margins of safety of 23.3- or 65-fold relative to respective plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair dyes containing PPD are unlikely to pose a health risk since they are used intermittently and systemic exposure is limited to the detoxified metabolite N,N'-diacetyl-PPD. PMID:25846501

  13. Antioxidant-Enhancing Property of the Polar Fraction of Mangosteen Pericarp Extract and Evaluation of Its Safety in Humans

    PubMed Central

    Numpraphrut, Pornpayom; Charoensakdi, Ratiya; Neungton, Neelobol; Tunrungruangtavee, Vachara; Jaisupa, Nattapon; Charoensak, Suwit

    2016-01-01

    Crude extract from the pericarp of the mangosteen (mangosteen extract [ME]) has exhibited several medicinal properties in both animal models and human cell lines. Interestingly, the cytotoxic activities were always observed in nonpolar fraction of the extract whereas the potent antioxidant was often found in polar fraction. Although it has been demonstrated that the polar fraction of ME exhibited the antioxidant activity, the safety of the polar fraction of ME has never been thoroughly investigated in humans. In this study, we investigated the safety of oral administration of the polar fraction of ME in 11 healthy Thai volunteers. During a 24-week period of the study, only minor and tolerable side effects were reported; no serious side effects were documented. Blood chemistry studies also showed no liver damage or kidney dysfunction in all subjects. We also demonstrated antioxidant property of the polar fraction of ME both in vitro and in vivo. Interestingly, oral administration of the polar fraction of ME enhanced the antioxidant capability of red blood cells and decreased oxidative damage to proteins within red blood cells and whole blood. PMID:27703599

  14. Transcriptome profiling of patient-specific human iPSC-cardiomyocytes predicts individual drug safety and efficacy responses in vitro

    PubMed Central

    Matsa, Elena; Burridge, Paul W.; Yu, Kun-Hsing; Ahrens, John H.; Termglinchan, Vittavat; Wu, Haodi; Liu, Chun; Shukla, Praveen; Sayed, Nazish; Churko, Jared M.; Shao, Ningyi; Woo, Nicole A.; Chao, Alexander S.; Gold, Joseph D.; Karakikes, Ioannis; Snyder, Michael P.; Wu, Joseph C.

    2016-01-01

    SUMMARY Understanding individual susceptibility to drug-induced cardiotoxicity is key to improving patient safety and preventing drug attrition. Human induced pluripotent stem cells (hiPSCs) enable the study of pharmacological and toxicological responses in patient-specific cardiomyocytes (CMs), and may serve as preclinical platforms for precision medicine. Transcriptome profiling in hiPSC-CMs from seven individuals lacking known cardiovascular disease-associated mutations, and in three isogenic human heart tissue and hiPSC-CM pairs, showed greater inter-patient variation than intra-patient variation, verifying that reprogramming and differentiation preserve patient-specific gene expression, particularly in metabolic and stress-response genes. Transcriptome-based toxicology analysis predicted and risk-stratified patient-specific susceptibility to cardiotoxicity, and functional assays in hiPSC-CMs using tacrolimus and rosiglitazone, drugs targeting pathways predicted to produce cardiotoxicity, validated inter-patient differential responses. CRISPR/Cas9-mediated pathway correction prevented drug-induced cardiotoxicity. Our data suggest that hiPSC-CMs can be used in vitro to predict and validate patient-specific drug safety and efficacy, potentially enabling future clinical approaches to precision medicine. PMID:27545504

  15. Acquisition and Extinction of Human Avoidance Behavior: Attenuating Effect of Safety Signals and Associations with Anxiety Vulnerabilities

    PubMed Central

    Sheynin, Jony; Beck, Kevin D.; Servatius, Richard J.; Myers, Catherine E.

    2014-01-01

    While avoidance behavior is often an adaptive strategy, exaggerated avoidance can be detrimental and result in the development of psychopathologies, such as anxiety disorders. A large animal literature shows that the acquisition and extinction of avoidance behavior in rodents depends on individual differences (e.g., sex, strain) and might be modulated by the presence of environmental cues. However, there is a dearth of such reports in human literature, mainly due to the lack of adequate experimental paradigms. In the current study, we employed a computer-based task, where participants control a spaceship and attempt to gain points by shooting an enemy spaceship that appears on the screen. Warning signals predict on-screen aversive events; the participants can learn a protective response to escape or avoid these events. This task has been recently used to reveal facilitated acquisition of avoidance behavior in individuals with anxiety vulnerability due to female sex or inhibited personality. Here, we extended the task to include an extinction phase, and tested the effect of signals that appeared during “safe” periods. Healthy young adults (n = 122) were randomly assigned to a testing condition with or without such signals. Results showed that the addition of safety signals during the acquisition phase impaired acquisition (in females) and facilitated extinction of the avoidance behavior. We also replicated our recent finding of an association between female sex and longer avoidance duration and further showed that females continued to demonstrate more avoidance behavior even on extinction trials when the aversive events no longer occurred. This study is the first to show sex differences on the acquisition and extinction of human avoidance behavior and to demonstrate the role of safety signals in such behavior, highlighting the potential relevance of safety signals for cognitive therapies that focus on extinction learning to treat anxiety symptoms. PMID

  16. Foods and food constituents that affect the brain and human behavior

    NASA Technical Reports Server (NTRS)

    Lieberman, Harris R.; Wurtman, Richard J.

    1986-01-01

    Until recently, it was generally believed that brain function was usually independent of day-to-day metabolic changes associated with consumption of food. Although it was acknowledged that peripheral metabolic changes associated with hunger or satiety might affect brain function, other effects of foods on the brain were considered unlikely. However, in 1971, Fernstrom and Wurtman discovered that under certain conditions, the protein-to-carbohydrate ratio of a meal could affect the concentration of a particular brain neurotransmitter. That neurotransmitter, serotonin, participates in the regulation of a variety of central nervous system (CNS) functions including sleep, pain sensitivity, aggression, and patterns of nutrient selection. The activity of other neurotransmitter systems has also been shown to be, under certain conditions, affected by dietary constituents which are given either as ordinary foods or in purified form. For example, the CNS turnover of two catecholamine neurotransmitters, dopamine and norepinephrine, can be altered by ingestion of their amino acid precursor, tyrosine, when neurons that release these monoamines are firing frequently. Similarly, lecithin, a dietary source of choline, and choline itself have been shown to increase the synthesis of acetylcholine when cholinergic neurons are very active. It is possible that other neurotransmitters could also be affected by precursor availability or other, as yet undiscovered peripheral factors governed by food consumption. The effects of food on neurotransmitters and behavior are discussed.

  17. Did warfare among ancestral hunter-gatherers affect the evolution of human social behaviors?

    PubMed

    Bowles, Samuel

    2009-06-01

    Since Darwin, intergroup hostilities have figured prominently in explanations of the evolution of human social behavior. Yet whether ancestral humans were largely "peaceful" or "warlike" remains controversial. I ask a more precise question: If more cooperative groups were more likely to prevail in conflicts with other groups, was the level of intergroup violence sufficient to influence the evolution of human social behavior? Using a model of the evolutionary impact of between-group competition and a new data set that combines archaeological evidence on causes of death during the Late Pleistocene and early Holocene with ethnographic and historical reports on hunter-gatherer populations, I find that the estimated level of mortality in intergroup conflicts would have had substantial effects, allowing the proliferation of group-beneficial behaviors that were quite costly to the individual altruist.

  18. Did warfare among ancestral hunter-gatherers affect the evolution of human social behaviors?

    PubMed

    Bowles, Samuel

    2009-06-01

    Since Darwin, intergroup hostilities have figured prominently in explanations of the evolution of human social behavior. Yet whether ancestral humans were largely "peaceful" or "warlike" remains controversial. I ask a more precise question: If more cooperative groups were more likely to prevail in conflicts with other groups, was the level of intergroup violence sufficient to influence the evolution of human social behavior? Using a model of the evolutionary impact of between-group competition and a new data set that combines archaeological evidence on causes of death during the Late Pleistocene and early Holocene with ethnographic and historical reports on hunter-gatherer populations, I find that the estimated level of mortality in intergroup conflicts would have had substantial effects, allowing the proliferation of group-beneficial behaviors that were quite costly to the individual altruist. PMID:19498163

  19. Human erythrocytes and neuroblastoma cells are affected in vitro by Au(III) ions.

    PubMed

    Suwalsky, Mario; González, Raquel; Villena, Fernando; Aguilar, Luis F; Sotomayor, Carlos P; Bolognin, Silvia; Zatta, Paolo

    2010-06-25

    Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl(3) was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 microM; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 microM concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 microm-1mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 microM to 100 microM. PMID:20580689

  20. Human erythrocytes and neuroblastoma cells are affected in vitro by Au(III) ions

    SciTech Connect

    Suwalsky, Mario; Gonzalez, Raquel; Villena, Fernando; Aguilar, Luis F.; Sotomayor, Carlos P.; Bolognin, Silvia; Zatta, Paolo

    2010-06-25

    Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl{sub 3} was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 {mu}M; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 {mu}M concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 {mu}m-1 mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 {mu}M to 100 {mu}M.

  1. Derivation of Trisomy 21 affected human embryonic stem cell line Genea021.

    PubMed

    Dumevska, Biljana; Bosman, Alexis; McKernan, Robert; Main, Heather; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea021 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analyses demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology, 71% of cells expressed Nanog, 84% Oct4, 23% Tra1-60 and 95% SSEA4, gave a Pluritest Pluripotency score of 21.85, Novelty of 1.42, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346003

  2. Derivation of Trisomy 21 affected human embryonic stem cell line Genea053.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea053 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analysis demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology and expressed pluripotent cell markers including 83% Nanog positive, 87% Oct4, 88% Tra1-60 and 98% SSEA4. The cell line was negative for Mycoplasma and visible contamination. PMID:27346024

  3. How Do ICT Uses and New Human Resources Practices Affect SMEs' Efficiency?

    NASA Astrophysics Data System (ADS)

    Castillo-Merino, David; Serradell-Lopez, Enric; González-González, Inés

    In this paper we have analyzed both the main traits of efficient firms and the main sources of firms' efficiency, through a representative sample of 2.029 small and medium size Catalan firms. Our results demonstrate the importance for entrepreneurs of realizing that firms' efficiency shows a significant improvement when advanced ICT uses are combined with human resources practices focused on the promotion of workers autonomy, flexibility and decentralization of firm's decision making process, and with the adoption of employees assessment systems based on human values.

  4. Derivation of Huntington Disease affected Genea091 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1.35. The cell line was negative for Mycoplasma and visible contamination. PMID:27346013

  5. Derivation of DM1 affected human embryonic stem cell line Genea067.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea067 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CTG repeats in the DMPK gene, indicative of Myotonic Dystrophy Type 1 (DM1). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 97% Oct4, 73% Tra1-60 and 98% SSEA4 and gave a Pluritest Pluripotency score of 25.75, Novelty of 1.46. The cell line was negative for Mycoplasma and visible contamination. PMID:27346009

  6. Derivation of DM2 affected human embryonic stem cell line Genea066.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea066 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CCTG repeats in exon 1 of the ZNF9 gene, indicative of Myotonic Dystrophy Type 2 (DM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 88% of cells expressed Nanog, 97% Oct4, 80% Tra1-60 and 99% SSEA4 and gave a Pluritest Pluripotency score of 31.3, Novelty of 1.22. The cell line was negative for Mycoplasma and visible contamination. PMID:27346023

  7. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346012

  8. Derivation of Huntington Disease affected Genea089 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1.2. The cell line was negative for Mycoplasma and visible contamination. PMID:27346008

  9. Derivation of Huntington Disease affected Genea090 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea090 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a pluritest pluripotency score of 30.91, novelty of 1.23. The cell line was negative for Mycoplasma and visible contamination. PMID:27346026

  10. Derivation of Huntington disease affected Genea020 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Peura, Teija; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346007

  11. Immunogenetic factors affecting susceptibility of humans and rodents to hantaviruses and the clinical course of hantaviral disease in humans.

    PubMed

    Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

    2014-05-26

    We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives.

  12. Growth Factor Content in Human Sera Affects the Isolation of Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

    PubMed Central

    Montali, Marina; Barachini, Serena; Panvini, Francesca M.; Carnicelli, Vittoria; Fulceri, Franca; Petrini, Iacopo; Pacini, Simone

    2016-01-01

    Mesangiogenic Progenitor Cells (MPCs) are human bone marrow-derived multipotent cells, isolated in vitro under selective culture conditions and shown to retain both mesengenic and angiogenic potential. MPCs also co-isolated with multipotent stromal cells (MSCs) when bone marrow primary cultures were set up for clinical applications, using human serum (HS) in place of fetal bovine serum (FBS). MPC culture purity (over 95%) is strictly dependent on HS supplementation with significant batch-to-batch variability. In the present paper we screened different sources of commercially available pooled human AB type serum (PhABS) for their ability to promote MPC production under selective culture conditions. As the majority of “contaminating” cells in MPC cultures were represented by MSC-like cells, we hypothesized a role by differentiating agents present in the sera. Therefore, we tested a number of growth factors (hGF) and found that higher concentrations of FGF-2, EGF, PDGF-AB, and VEGF-A as well as lower concentration of IGF-1 give sub-optimal MPC recovery. Gene expression analysis of hGF receptors was also carried out both in MSCs and MPCs, suggesting that FGF-2, EGF, and PDGF-AB could act promoting MSC proliferation, while VEGF-A contribute to MSC-like cell contamination, triggering MPC differentiation. Here we demonstrated that managing hGF contents, together with applying specific receptors inhibitors (Erlotinib-HCl and Nintedanib), could significantly mitigate the batch-to-batch variability related to serum supplementation. These data represent a fundamental milestone in view of manufacturing MPC-based medicinal products. PMID:27800477

  13. Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

    PubMed Central

    Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

    2014-01-01

    We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. PMID:24859344

  14. Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.

    PubMed

    Meneghini, Vasco; Lattanzi, Annalisa; Tiradani, Luigi; Bravo, Gabriele; Morena, Francesco; Sanvito, Francesca; Calabria, Andrea; Bringas, John; Fisher-Perkins, Jeanne M; Dufour, Jason P; Baker, Kate C; Doglioni, Claudio; Montini, Eugenio; Bunnell, Bruce A; Bankiewicz, Krystof; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2016-05-02

    Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD.

  15. Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.

    PubMed

    Meneghini, Vasco; Lattanzi, Annalisa; Tiradani, Luigi; Bravo, Gabriele; Morena, Francesco; Sanvito, Francesca; Calabria, Andrea; Bringas, John; Fisher-Perkins, Jeanne M; Dufour, Jason P; Baker, Kate C; Doglioni, Claudio; Montini, Eugenio; Bunnell, Bruce A; Bankiewicz, Krystof; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2016-01-01

    Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD. PMID

  16. N-Methyl D-Aspartate Receptor Antagonist Kynurenic Acid Affects Human Cortical Development

    PubMed Central

    Bagasrawala, Inseyah; Zecevic, Nada; Radonjić, Nevena V.

    2016-01-01

    Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated levels of KYNA have been observed in pregnant women after viral infections and are considered to play a role in neurodevelopmental disorders. However, the consequences of KYNA-induced NMDAR blockade in human cortical development still remain elusive. To study the potential impact of KYNA on human neurodevelopment, we used an in vitro system of multipotent cortical progenitors, i.e., radial glia cells (RGCs), enriched from human cerebral cortex at mid-gestation (16–19 gestational weeks). KYNA treatment significantly decreased RGCs proliferation and survival by antagonizing NMDAR. This alteration resulted in a reduced number of cortical progenitors and neurons while number and activation of astrocytes increased. KYNA treatment reduced differentiation of RGCs into GABAergic neurons, while differentiation into glutamatergic neurons was relatively spared. Furthermore, in mixed cortical cultures KYNA triggered an inflammatory response as evidenced by increased levels of the pro-inflammatory cytokine IL-6. In conclusion, elevated levels of KYNA play a significant role in human RGC fate determination by antagonizing NMDARs and by activating an inflammatory response. The altered cell composition observed in cell culture following exposure to elevated KYNA levels suggests a mechanism for impairment of cortical circuitry formation in the fetal brain after viral infection, as seen in neurodevelopmental disorders such as schizophrenia. PMID:27746712

  17. CULTURE CONDITIONS AFFECT HUMAN AIRWAY EPITHELIAL CELL RESPONSE TO DIESEL PARTICLE EXPOSURE IN VITRO

    EPA Science Inventory

    Diesel exhaust particles (DEP) are a ubiquitous ambient air contaminant that may contribute to the health effects of particulate matter inhalation. In vitro studies have shown that DEP exposure induces pro-inflammatory proteins in human airway epithelial cells (HAEC) with varying...

  18. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

    PubMed Central

    Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

    2015-01-01

    Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

  19. [Affective behavioural responses by dogs to tactile human-dog interactions].

    PubMed

    Kuhne, Franziska; Hössler, Johanna C; Struwe, Rainer

    2012-01-01

    The communication of dogs is based on complex, subtle body postures and facial expressions. Some social interaction between dogs includes physical contact. Humans generally use both verbal and tactile signals to communicate with dogs. Hence, interaction between humans and dogs might lead to conflicts because the behavioural responses of dogs to human-dog interaction may be misinterpreted and wrongly assessed. The behavioural responses of dogs to tactile human-dog interactions and human gestures are the focus of this study. The participating dogs (n = 47) were privately owned pets.They were of varying breed and gender.The test consisted of nine randomised test sequences (e. g. petting the dog's head or chest). A test sequence was performed for a period of 30 seconds. The inter-trial interval was set at 60 seconds and the test-retest interval was set at 10 minutes. The frequency and duration of the dogs'behavioural responses were recorded using INTERACT. To examine the behavioural responses of the dogs, a two-way analysis of variance within the linear mixed models procedure of IBM SPSS Statistics 19 was conducted. A significant influence of the test-sequenc order on the dogs' behaviour could be analysed for appeasement gestures (F8,137 = 2.42; p = 0.018), redirected behaviour (F8,161 = 6.31; p = 0.012) and socio-positive behaviour (F8,148 = 6.28; p = 0.012). The behavioural responses of the dogs, which were considered as displacement activities (F8,109 = 2.5; p = 0.014) differed significantly among the test sequences. The response of the dogs, measured as gestures of appeasement, redirected behaviours, and displacement activities, was most obvious during petting around the head and near the paws.The results of this study conspicuously indicate that dogs respond to tactile human-dog interactions with gestures of appeasement and displacement activities. Redirected behaviours, socio-positive behaviours as well displacement activities are behavioural responses which dogs

  20. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

    PubMed Central

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C. Nathan; Mandell, Dorothy; Burbacher, Thomas M.; Sackett, Gene P.

    2015-01-01

    Background In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. Objectives The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. Results We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. Conclusions This comprehensive 5-year case–control study, which closely examined

  1. Human-rated Safety Certification of a High Voltage Robonaut Lithium-ion Battery

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Judith; Yayathi, S.; Johnson, M.; Waligora, T.; Verdeyen, W.

    2013-01-01

    NASA's rigorous certification process is being followed for the R2 high voltage battery program for use of R2 on International Space Station (ISS). Rigorous development testing at appropriate levels to credible off-nominal conditions and review of test data led to design improvements for safety at the virtual cell, cartridge and battery levels. Tests were carried out at all levels to confirm that both hardware and software controls work. Stringent flight acceptance testing of the flight battery will be completed before launch for mission use on ISS.

  2. Occupational demand and human rights. Public safety officers and cardiorespiratory fitness.

    PubMed

    Shephard, R J

    1991-08-01

    The issue of discrimination in physically demanding employment, such as police, firefighters, prison guards and military personnel, is contentious. In terms of oxygen transport, the 'action limit' (calling for personnel selection or task redesign) is a steady oxygen consumption of 0.7 L/min, while the maximum permissible limit is 2.1 L/min. Note is taken of the commonly expressed belief that public safety duties are physically demanding, calling for personnel with an aerobic power of at least 3 L/min, or 42 to 45 ml/kg/min. The actual demands of such work can be assessed on small samples by physiological measurements (using heart rate or oxygen consumption meters), but the periods sampled may not be typical of a normal day. A Gestalt can also be formed as to the heaviness of a given job, or a detailed task analysis can be performed; most such analyses of public safety work list distance running and other aerobic activities infrequently. An arbitrary requirement of 'above average fitness' is no longer accepted by courts, but a further approach is to examine the characteristics of those currently meeting the demands of public safety jobs satisfactorily. Young men commonly satisfy the 3 L/min standard, but this is not usually the case for women or older men; in the case of female employees, it also seems unreasonable that they should be expected to satisfy the same standards as men, since a lower body mass reduces the energy cost of most of the tasks that they must perform. A second criterion sometimes applied to physically demanding work (a low vulnerability to heart attacks) is examined critically. It is concluded that the chances that a symptom-free public safety officer will develop a heart attack during a critical solo mission are so low that cardiac risk should not be a condition of employment. Arbitrary age- and sex-related employment criteria are plainly discriminatory, since some women and 65-year-old men have higher levels of physical fitness than the

  3. Muecas: a multi-sensor robotic head for affective human robot interaction and imitation.

    PubMed

    Cid, Felipe; Moreno, Jose; Bustos, Pablo; Núñez, Pedro

    2014-01-01

    This paper presents a multi-sensor humanoid robotic head for human robot interaction. The design of the robotic head, Muecas, is based on ongoing research on the mechanisms of perception and imitation of human expressions and emotions. These mechanisms allow direct interaction between the robot and its human companion through the different natural language modalities: speech, body language and facial expressions. The robotic head has 12 degrees of freedom, in a human-like configuration, including eyes, eyebrows, mouth and neck, and has been designed and built entirely by IADeX (Engineering, Automation and Design of Extremadura) and RoboLab. A detailed description of its kinematics is provided along with the design of the most complex controllers. Muecas can be directly controlled by FACS (Facial Action Coding System), the de facto standard for facial expression recognition and synthesis. This feature facilitates its use by third party platforms and encourages the development of imitation and of goal-based systems. Imitation systems learn from the user, while goal-based ones use planning techniques to drive the user towards a final desired state. To show the flexibility and reliability of the robotic head, the paper presents a software architecture that is able to detect, recognize, classify and generate facial expressions in real time using FACS. This system has been implemented using the robotics framework, RoboComp, which provides hardware-independent access to the sensors in the head. Finally, the paper presents experimental results showing the real-time functioning of the whole system, including recognition and imitation of human facial expressions. PMID:24787636

  4. Muecas: a multi-sensor robotic head for affective human robot interaction and imitation.

    PubMed

    Cid, Felipe; Moreno, Jose; Bustos, Pablo; Núñez, Pedro

    2014-04-28

    This paper presents a multi-sensor humanoid robotic head for human robot interaction. The design of the robotic head, Muecas, is based on ongoing research on the mechanisms of perception and imitation of human expressions and emotions. These mechanisms allow direct interaction between the robot and its human companion through the different natural language modalities: speech, body language and facial expressions. The robotic head has 12 degrees of freedom, in a human-like configuration, including eyes, eyebrows, mouth and neck, and has been designed and built entirely by IADeX (Engineering, Automation and Design of Extremadura) and RoboLab. A detailed description of its kinematics is provided along with the design of the most complex controllers. Muecas can be directly controlled by FACS (Facial Action Coding System), the de facto standard for facial expression recognition and synthesis. This feature facilitates its use by third party platforms and encourages the development of imitation and of goal-based systems. Imitation systems learn from the user, while goal-based ones use planning techniques to drive the user towards a final desired state. To show the flexibility and reliability of the robotic head, the paper presents a software architecture that is able to detect, recognize, classify and generate facial expressions in real time using FACS. This system has been implemented using the robotics framework, RoboComp, which provides hardware-independent access to the sensors in the head. Finally, the paper presents experimental results showing the real-time functioning of the whole system, including recognition and imitation of human facial expressions.

  5. Muecas: A Multi-Sensor Robotic Head for Affective Human Robot Interaction and Imitation

    PubMed Central

    Cid, Felipe; Moreno, Jose; Bustos, Pablo; Núñez, Pedro

    2014-01-01

    This paper presents a multi-sensor humanoid robotic head for human robot interaction. The design of the robotic head, Muecas, is based on ongoing research on the mechanisms of perception and imitation of human expressions and emotions. These mechanisms allow direct interaction between the robot and its human companion through the different natural language modalities: speech, body language and facial expressions. The robotic head has 12 degrees of freedom, in a human-like configuration, including eyes, eyebrows, mouth and neck, and has been designed and built entirely by IADeX (Engineering, Automation and Design of Extremadura) and RoboLab. A detailed description of its kinematics is provided along with the design of the most complex controllers. Muecas can be directly controlled by FACS (Facial Action Coding System), the de facto standard for facial expression recognition and synthesis. This feature facilitates its use by third party platforms and encourages the development of imitation and of goal-based systems. Imitation systems learn from the user, while goal-based ones use planning techniques to drive the user towards a final desired state. To show the flexibility and reliability of the robotic head, the paper presents a software architecture that is able to detect, recognize, classify and generate facial expressions in real time using FACS. This system has been implemented using the robotics framework, RoboComp, which provides hardware-independent access to the sensors in the head. Finally, the paper presents experimental results showing the real-time functioning of the whole system, including recognition and imitation of human facial expressions. PMID:24787636

  6. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    PubMed

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

    2015-06-17

    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

  7. Fate of ingested fluids: factors affecting gastric emptying and intestinal absorption of beverages in humans.

    PubMed

    Leiper, John B

    2015-09-01

    The volume of fluid ingested for rehydration is essential in determining the restoration of euhydration because it must be in excess of the water lost since the individual was last euhydrated. The formulation of any ingested beverage is also important as this affects the rate at which the fluid is emptied from the stomach, absorbed in the small intestine, and hence assimilated into the body water pool. This review highlights the essential role of the gastrointestinal tract in the maintenance of hydration status.

  8. Interrelationships of food safety and plant pathology: the life cycle of human pathogens on plants.

    PubMed

    Barak, Jeri D; Schroeder, Brenda K

    2012-01-01

    Bacterial food-borne pathogens use plants as vectors between animal hosts, all the while following the life cycle script of plant-associated bacteria. Similar to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain pathogens have a foothold in agricultural production areas. The commonality of environmental contamination translates to contact with plants. Because of the chronic absence of kill steps against human pathogens for fresh produce, arrival on plants leads to persistence and the risk of human illness. Significant research progress is revealing mechanisms used by human pathogens to colonize plants and important biological interactions between and among bacteria in planta. These findings articulate the difficulty of eliminating or reducing the pathogen from plants. The plant itself may be an untapped key to clean produce. This review highlights the life of human pathogens outside an animal host, focusing on the role of plants, and illustrates areas that are ripe for future investigation.

  9. The safety of modafinil in combination with oral ∆9-tetrahydrocannabinol in humans.

    PubMed

    Sugarman, Dawn E; Poling, James; Sofuoglu, Mehmet

    2011-03-01

    Marijuana (cannabis) is the most widely used illicit substance globally, and cannabis use is associated with a range of adverse consequences. Currently, no medications have been proven to be effective for the treatment of cannabis addiction. The goals of this study were to examine the safety and efficacy of a potential treatment medication, modafinil, in combination with oral ∆9-tetrahydrocannabinol (THC). Twelve male and female occasional cannabis users participated in an outpatient double-blind, placebo-controlled, crossover study. Across four sessions, participants were randomly assigned to a sequence of four oral treatments: (1) 400 mg modafinil+placebo, (2) 15 mg THC+placebo, (3) 400 mg modafinil+15 mg THC, or (4) placebo+placebo. Outcome measures included heart rate, blood pressure, performance on the Rapid Visual Information Processing (RVIP), and the Hopkins Verbal Learning Test (HVLT), and subjective measures. Oral THC increased heart rate, and produced increased subjective ratings of feeling "high" and "sedated," as well as increased ratings of euphoria. Modafinil alone increased the Profiles of Mood States (POMS) subscales of vigor and tension. These findings support the safety of modafinil in combination with THC. The effects of modafinil in combination with a range of doses of THC need to be determined in future studies. PMID:21176784

  10. A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers.

    PubMed

    Dole, Kiran; Segal, Florencia Pereyra; Feire, Adam; Magnusson, Baldur; Rondon, Juan C; Vemula, Janardhana; Yu, Jing; Pang, Yinuo; Pertel, Peter

    2016-05-01

    Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

  11. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    PubMed Central

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  12. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    PubMed

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  13. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    PubMed

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  14. Factors affecting the human-feeding behavior of anopheline mosquitoes in Egyptian oases.

    PubMed

    Kenawy, M A; Beier, J C; Asiago, C M; el Said, S

    1990-09-01

    Blood meals were tested by a direct enzyme-linked immunosorbent assay (ELISA) for 424 Anopheles sergentii and for 63 An. multicolor collected in Siwa, Farafra and Bahariya oases in the Western Desert of Egypt. Both species were highly zoophilic. Human blood-feeding by An. sergentii was less common in Bahariya (2.3%) and Farafra (1.3%) than in Siwa (15.3%). A likely explanation is that large domestic animals are held at night inside houses in Bahariya and in Farafra whereas in Siwa, animals are usually housed outdoors in sheds. These patterns of An. sergentii human-feeding behavior may contribute to the persistence of low-level Plasmodium vivax transmission in Siwa in contrast to negligible or no transmission in Bahariya and Farafra.

  15. TGF-β affects development and differentiation of human natural killer cell subsets

    PubMed Central

    Allan, David S.J.; Rybalov, Basya; Awong, Génève; Zúñiga-Pflücker, Juan Carlos; Kopcow, Hernan D.; Carlyle, James R.; Strominger, Jack L.

    2011-01-01

    Summary Human peripheral blood NK cells may be divided into two main subsets: CD56brightCD16− and CD56dimCD16+. Since TGF-β is known to influence the development of many leukocyte lineages, its effects on NK cell differentiation either from human CD34+Lin− hematopoietic progenitor/stem cells in vitro or from peripheral blood NK cells were investigated. TGF-β represses development of NK cells from CD34+ progenitors and inhibits differentiation of CD16+ NK cells. Moreover, TGF-β also results in conversion of a minor fraction of CD56brightCD16+ cells found in peripheral blood into CD56brightCD16− cells, highlighting a possible role of the former as a developmental intermediate and of TGF-β in influencing the genesis of NK subsets found in blood. PMID:20540115

  16. Visual short-term memory load affects sensory processing of irrelevant sounds in human auditory cortex.

    PubMed

    Valtonen, Jussi; May, Patrick; Mäkinen, Ville; Tiitinen, Hannu

    2003-07-01

    We used whole-head magnetoencephalography (MEG) to investigate neural activity in human auditory cortex elicited by irrelevant tones while the subjects were engaged in a short-term memory task presented in the visual modality. As compared to a no-memory-task condition, memory load enhanced the amplitude of the auditory N1m response. In addition, the N1m amplitude depended on the phase of the memory task, with larger response amplitudes observed during encoding than retention. Further, these amplitude modulations were accompanied by anterior-posterior shifts in N1m source locations. The results show that a memory task for visually presented stimuli alters sensory processing in human auditory cortex, even when subjects are explicitly instructed to ignore any auditory stimuli. Thus, it appears that task demands requiring attentional allocation and short-term memory result in interaction across visual and auditory brain areas carrying out the processing of stimulus features.

  17. Derivation of NEM2 affected human embryonic stem cell line Genea079.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea079 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 86% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 98% SSEA4 and gave a PluriTest Pluripotency score of 30.25, Novelty of 1.21. The cell line was negative for Mycoplasma and visible contamination. PMID:27346010

  18. Derivation of NEM2 affected human embryonic stem cell line Genea080.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea080 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 99% SSEA4 and gave a PluriTest Pluripotency score of 32.08, Novelty of 1.3. The cell line was negative for Mycoplasma and visible contamination. PMID:27346011

  19. Derivation of NEM2 affected human embryonic stem cell line Genea078.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea078 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 76% of cells expressed Nanog, 93% Oct4, 67% Tra1-60 and 97% SSEA4 and gave a Pluritest Pluripotency score of 42.18, Novelty of 1.37. The cell line was negative for Mycoplasma and visible contamination. PMID:27346006

  20. Derivation of FSHD1 affected human embryonic stem cell line Genea049.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea049 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 96% Oct4, 80% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 23.16, Novelty of 1.43 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346016

  1. Derivation of Huntington Disease affected Genea017 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346022

  2. Derivation of FSHD1 affected human embryonic stem cell line Genea050.

    PubMed

    Dumevska, Biljana; Chami, Omar; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea050 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 25.45, Novelty of 1.45 demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346025

  3. Derivation of FSHD1 affected human embryonic stem cell line Genea096.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea096 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 6 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 64% of cells expressed Nanog, 93% Oct4, 58% Tra1-60 and 93% SSEA4 and a Pluritest Pluripotency score of 39.41, Novelty of 1.25. The cell line was negative for Mycoplasma and visible contamination. PMID:27346027

  4. Derivation of Huntington Disease affected Genea018 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346005

  5. What affects facing direction in human facial profile drawing? A meta-analytic inquiry.

    PubMed

    Tosun, Sümeyra; Vaid, Jyotsna

    2014-01-01

    Two meta-analyses were conducted to examine two potential sources of spatial orientation biases in human profile drawings by brain-intact individuals. The first examined profile facing direction as function of hand used to draw. The second examined profile facing direction in relation to directional scanning biases related to reading/writing habits. Results of the first meta-analysis, based on 27 study samples with 4171 participants, showed that leftward facing of profiles (from the viewer's perspective) was significantly associated with using the right hand to draw. The reading/writing direction meta-analysis, based on 10 study samples with 1552 participants, suggested a modest relationship between leftward profile facing and primary use of a left-to-right reading/writing direction. These findings suggest that biomechanical and cultural factors jointly influence hand movement preferences and in turn the direction of facing of human profile drawings.

  6. Resveratrol affects DNA damage induced by ionizing radiation in human lymphocytes in vitro.

    PubMed

    Basso, Emiliano; Regazzo, Giulia; Fiore, Mario; Palma, Valentina; Traversi, Gianandrea; Testa, Antonella; Degrassi, Francesca; Cozzi, Renata

    2016-08-01

    Resveratrol (3,4',5-trihydroxystilbene; RSV) acts on cancer cells in several ways, inducing cell cycle delay and apoptotic death, and enhancing ionizing radiation (IR)-mediated responses. However, fewer studies have examined RSV effects on normal cells. We have treated human lymphocytes in vitro with RSV, either alone or combined with IR, to evaluate its potential use as a radioprotector. We measured the effects of RSV on induction of DNA damage, repair kinetics, and modulation of histone deacetylase activity. PMID:27476334

  7. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers.

    PubMed

    Blarquez, Olivier; Ali, Adam A; Girardin, Martin P; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-09-02

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees.

  8. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  9. Human TREX component Thoc5 affects alternative polyadenylation site choice by recruiting mammalian cleavage factor I

    PubMed Central

    Katahira, Jun; Okuzaki, Daisuke; Inoue, Hitomi; Yoneda, Yoshihiro; Maehara, Kazumitsu; Ohkawa, Yasuyuki

    2013-01-01

    The transcription-export complex (TREX) couples mRNA transcription, processing and nuclear export. We found that CFIm68, a large subunit of a heterotetrameric protein complex mammalian cleavage factor I (CFIm), which is implicated in alternative polyadenylation site choice, co-purified with Thoc5, a component of human TREX. Immunoprecipitation using antibodies against different components of TREX indicated that most likely both complexes interact via an interaction between Thoc5 and CFIm68. Microarray analysis using human HeLa cells revealed that a subset of genes was differentially expressed on Thoc5 knockdown. Notably, the depletion of Thoc5 selectively attenuated the expression of mRNAs polyadenylated at distal, but not proximal, polyadenylation sites, which phenocopied the depletion of CFIm68. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) indicated that CFIm68 preferentially associated with the 5′ regions of genes; strikingly, the 5′ peak of CFIm68 was significantly and globally reduced on Thoc5 knockdown. We suggest a model in which human Thoc5 controls polyadenylation site choice through the co-transcriptional loading of CFIm68 onto target genes. PMID:23685434

  10. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers

    PubMed Central

    Blarquez, Olivier; Ali, Adam A.; Girardin, Martin P.; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-01-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees. PMID:26330162

  11. The antiepileptic drug diphenylhydantoin affects the structure of the human erythrocyte membrane.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Villena, Fernando; Cuevas, Francisco; Sotomayor, Carlos P

    2004-01-01

    Phenytoin (diphenylhydantoin) is an antiepileptic agent effective against all types of partial and tonic-clonic seizures. Phenytoin limits the repetitive firing of action potentials evoked by a sustained depolarization of mouse spinal cord neurons maintained in vitro. This effect is mediated by a slowing of the rate of recovery of voltage activated Na+ channels from inactivation. For this reasons it was thought of interest to study the binding affinities of phenytoin with cell membranes and their perturbing effects upon membrane structures. The effects of phenytoin on the human erythrocyte membrane and molecular models have been investigated in the present work. This report presents the following evidence that phenytoin interacts with cell membranes: a) X-ray diffraction and fluorescence spectroscopy of phospholipid bilayers showed that phenytoin perturbed a class of lipids found in the outer moiety of cell membranes; b) in isolated unsealed human erythrocyte membranes (IUM) the drug induced a disordering effect on the polar head groups and acyl chains of the erythrocyte membrane lipid bilayer; c) in scanning electron microscopy (SEM) studies on human erythrocytes the formation of echinocytes was observed, due to the insertion of phenytoin in the outer monolayer of the red cell membrane. This is the first time that an effect of phenytoin on the red cell shape is described. However, the effects of the drug were observed at concentrations higher than those currently found in plasma when phenytoin is therapeutically administered. PMID:18998414

  12. Atrazine Affects Phosphoprotein and Protein Expression in MCF-10A Human Breast Epithelial Cells

    PubMed Central

    Huang, Peixin; Yang, John; Song, Qisheng; Sheehan, David

    2014-01-01

    Atrazine, a member of the 2-chloro-s-triazine family of herbicides, is the most widely used pesticide in the world and often detected in agriculture watersheds. Although it was generally considered as an endocrine disruptor, posing a potential threat to human health, the molecular mechanisms of atrazine effects remain unclear. Using two-dimensional gel electrophoresis, we identified a panel of differentially expressed phosphoproteins and total proteins in human breast epithelial MCF-10A cells after being exposed to environmentally relevant concentrations of atrazine. Atrazine treatments for 6 h resulted in differential expression of 4 phosphoproteins and 8 total-proteins as compared to the control cells (>1.5-fold, p < 0.05). MALDI-TOF MS/MS analysis revealed that the differentially expressed proteins belong to various cellular compartments (nucleus, cytosol, membrane) and varied in function, including those regulating the stress response such as peroxiredoxin I, HSP70 and HSP27; structural proteins such as tropomyosin and profilin 1; and oncogenesis proteins such as ANP32A. Six of the 12 identified proteins were verified by quantitative PCR for their transcript levels. The most up-regulated phosphoprotein by atrazine treatment, ANP32A, was further analyzed for its expression, distribution and cellular localization using Western blot and immunocytochemical approaches. The results revealed that ANP32 expression after atrazine treatment increased dose and time dependently and was primarily located in the nucleus. This study may provide new evidence on the potential toxicity of atrazine in human cells. PMID:25275270

  13. Atrazine affects phosphoprotein and protein expression in MCF-10A human breast epithelial cells.

    PubMed

    Huang, Peixin; Yang, John; Song, Qisheng

    2014-10-01

    Atrazine, a member of the 2-chloro-s-triazine family of herbicides, is the most widely used pesticide in the world and often detected in agriculture watersheds. Although it was generally considered as an endocrine disruptor, posing a potential threat to human health, the molecular mechanisms of atrazine effects remain unclear. Using two-dimensional gel electrophoresis, we identified a panel of differentially expressed phosphoproteins and total proteins in human breast epithelial MCF-10A cells after being exposed to environmentally relevant concentrations of atrazine. Atrazine treatments for 6 h resulted in differential expression of 4 phosphoproteins and 8 total-proteins as compared to the control cells (>1.5-fold, p<0.05). MALDI-TOF MS/MS analysis revealed that the differentially expressed proteins belong to various cellular compartments (nucleus, cytosol, membrane) and varied in function, including those regulating the stress response such as peroxiredoxin I, HSP70 and HSP27; structural proteins such as tropomyosin and profilin 1; and oncogenesis proteins such as ANP32A. Six of the 12 identified proteins were verified by quantitative PCR for their transcript levels. The most up-regulated phosphoprotein by atrazine treatment, ANP32A, was further analyzed for its expression, distribution and cellular localization using Western blot and immunocytochemical approaches. The results revealed that ANP32 expression after atrazine treatment increased dose and time dependently and was primarily located in the nucleus. This study may provide new evidence on the potential toxicity of atrazine in human cells.

  14. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington's disease.

    PubMed

    Zuccato, Chiara; Marullo, Manuela; Conforti, Paola; MacDonald, Marcy E; Tartari, Marzia; Cattaneo, Elena

    2008-04-01

    One cardinal feature of Huntington's disease (HD) is the degeneration of striatal neurons, whose survival greatly depends on the binding of cortical brain-derived neurotrophic factor (BDNF) with high-affinity (TrkB) and low-affinity neurotrophin receptors [p75 pan-neurotrophin receptor (p75(NTR))]. With a few exceptions, results obtained in HD mouse models demonstrate a reduction in cortical BDNF mRNA and protein, although autopsy data from a limited number of human HD cortices are conflicting. These studies indicate the presence of defects in cortical BDNF gene transcription and transport to striatum. We provide new evidence indicating a significant reduction in BDNF mRNA and protein in the cortex of 20 HD subjects in comparison with 17 controls, which supports the hypothesis of impaired BDNF production in human HD cortex. Analyses of the BDNF isoforms show that transcription from BDNF promoter II and IV is down-regulated in human HD cortex from an early symptomatic stage. We also found that TrkB mRNA levels are reduced in caudate tissue but not in the cortex, whereas the mRNA levels of T-Shc (a truncated TrkB isoform) and p75(NTR) are increased in the caudate. This indicates that, in addition to the reduction in BDNF mRNA, there is also unbalanced neurotrophic receptor signaling in HD. PMID:18093249

  15. Placental CLIC3 is increased in fetal growth restriction and pre-eclampsia affected human pregnancies.

    PubMed

    Murthi, P; Stevenson, J L; Money, T T; Borg, A J; Brennecke, S P; Gude, N M

    2012-09-01

    Chloride intracellular channel (CLIC) proteins constitute a subgroup of the glutathione-S-transferase (GSTs) superfamily. In humans, the CLIC family of proteins consists of six members, designated CLIC 1-6, which have a conserved C-terminal 240 residue module and one major transmembrane domain. CLIC proteins regulate fundamental cellular processes including regulation of chloride ion concentration, stabilization of cell membrane potential, trans-epithelial transport, regulation of cell volume and stimulation of apoptotic processes in response to cellular stress. Previously, we described the expression profile of a member of the CLIC family of proteins, CLIC3, in human placentae and fetal membranes. In the current study, we determined CLIC3 expression in placentae from pregnancies complicated with either fetal growth restriction (FGR, n=19), pre-eclampsia (PE, n=16) or both FGR and PE combined (n=12) compared to gestation-matched controls (n=13) using real-time PCR and a CLIC3 specific immunoassay. Significantly increased CLIC3 mRNA and protein were detected in placental extracts from pregnancies with FGR, PE and PE with FGR compared to controls. Our results suggest that increased expression of CLIC3 may play a role in abnormal placental function associated with the human pregnancy disorders FGR and PE. PMID:22795578

  16. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers.

    PubMed

    Blarquez, Olivier; Ali, Adam A; Girardin, Martin P; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-01-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees. PMID:26330162

  17. Human brain EEG indices of emotions: delineating responses to affective vocalizations by measuring frontal theta event-related synchronization.

    PubMed

    Bekkedal, Marni Y V; Rossi, John; Panksepp, Jaak

    2011-10-01

    At present there is no direct brain measure of basic emotional dynamics from the human brain. EEG provides non-invasive approaches for monitoring brain electrical activity to emotional stimuli. Event-related desynchronization/synchronization (ERD/ERS) analysis, based on power shifts in specific frequency bands, has some potential as a method for differentiating responses to basic emotions as measured during brief presentations of affective stimuli. Although there appears to be fairly consistent theta ERS in frontal regions of the brain during the earliest phases of processing affective auditory stimuli, the patterns do not readily distinguish between specific emotions. To date it has not been possible to consistently differentiate brain responses to emotion-specific affective states or stimuli, and some evidence to suggests the theta ERS more likely measures general arousal processes rather than yielding veridical indices of specific emotional states. Perhaps cortical EEG patterns will never be able to be used to distinguish discrete emotional states from the surface of the brain. The implications and limitations of such approaches for understanding human emotions are discussed. PMID:21596060

  18. Crucial Dimensions of Human Altruism. Affective vs. Conceptual Factors Leading to Helping or Reinforcing Others.

    PubMed

    Szuster, Anna

    2016-01-01

    The aim of this article is to identify factors leading to favorable attitudes toward other people from different social categories. The parts of article reflect diverse levels of altruism regulation from primary affective responses to the environment, through social norms, to abstract moral concepts related to good and evil. The latter allow understanding of the perspective of other people (including those belonging to out-groups), acceptance of their values and engagement not only in helping behavior but also in supporting the development of others. PMID:27148127

  19. Crucial Dimensions of Human Altruism. Affective vs. Conceptual Factors Leading to Helping or Reinforcing Others

    PubMed Central

    Szuster, Anna

    2016-01-01

    The aim of this article is to identify factors leading to favorable attitudes toward other people from different social categories. The parts of article reflect diverse levels of altruism regulation from primary affective responses to the environment, through social norms, to abstract moral concepts related to good and evil. The latter allow understanding of the perspective of other people (including those belonging to out-groups), acceptance of their values and engagement not only in helping behavior but also in supporting the development of others. PMID:27148127

  20. An analysis of the use of animal models in predicting human toxicology and drug safety.

    PubMed

    Bailey, Jarrod; Thew, Michelle; Balls, Michael

    2014-06-01

    Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1-4 biomedical observations. This was done for three preclinical species (rat, mouse and rabbit), to augment our previously-published analysis of canine data. In common with our dog analysis, the resulting LRs show: a) that the absence of toxicity in the animal provides little or virtually no evidential weight that adverse drug reactions (ADRs) will also be absent in humans; and b) that, while the presence of toxicity in these species can add considerable evidential weight for human risk, the LRs are extremely inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Therefore, our results for these additional preclinical species have important implications for their use in predicting human toxicity, and suggest that alternative methods are urgently required.

  1. Does testosterone affect lateralization of brain and behaviour? A meta-analysis in humans and other animal species.

    PubMed

    Pfannkuche, Kristina A; Bouma, Anke; Groothuis, Ton G G

    2009-04-12

    Lateralization of brain and behaviour has been the topic of research for many years in neuropsychology, but the factors guiding its development remain elusive. Based on sex differences in human lateralization, four hypotheses have been postulated that suggest a role for androgens, specifically testosterone. With the discovery that lateralization is a fundamental principle in the organization of brain and behaviour among vertebrates, it has now become possible to experimentally test such hypotheses in animal models. The use of different taxa, humans, other mammalian species and birds (with oestradiol and not testosterone involved in sexual differentiation in birds) facilitates to differentiate between the hypotheses. We used meta-analyses for analysing papers that provided sufficient information, and a semi-quantitative approach based on all relevant studies that we extracted from the literature. We tested the predictions of these hypotheses regarding strength and direction of lateralization for motor output, language and visuospatial cognition in these three taxa. We tested for sex differences and early organizational effects of testosterone (both correlative and experimental studies). We found sex differences in the direction of lateralization for non-human mammals (motor biases similar to humans) and in direction and strength in birds (visual cognitive tasks). However, the prediction that prenatal testosterone exposure affects the direction of lateralization was not supported for humans. In birds and non-human mammals, opposite trends were found, with the effect in non-human mammals being opposite to the expectation based on sex differences. None of the four hypotheses was sufficiently supported and more studies, testing a wider array of functions in different taxa while reporting the data more completely are needed. PMID:19064349

  2. Discovering Innovation at the Intersection of Undergraduate Medical Education, Human Factors, and Collaboration: The Development of a Nasogastric Tube Safety Pack

    PubMed Central

    Bamford, Thomas; Haindl, Cornelia; Cracknell, Alison

    2016-01-01

    Problem Significant deficiencies exist in the knowledge and skills of medical students and residents around health care quality and safety. The theory and practice of quality and safety should be embedded into undergraduate medical practice so that health care professionals are capable of developing interventions and innovations to effectively anticipate and mitigate errors. Approach Since 2011, Leeds Medical School in the United Kingdom has used case study examples of nasogastric (NG) tube patient safety incidents within the undergraduate patient safety curriculum. In 2012, a medical undergraduate student approached a clinician with an innovative idea after undertaking an NG tubes root cause analysis case study. Simultaneously, a separate local project demonstrated low compliance (11.6%) with the United Kingdom’s National Patient Safety Agency NG tubes guideline for use of the correct method to check tube position. These separate endeavors led to interdisciplinary collaboration between a medical student, health care professionals, researchers, and industry to develop the Initial Placement Nasogastric Tube Safety Pack. Outcomes Human factors engineering was used to inform pack design to allow guideline recommendations to be accessible and easy to follow. A timeline of product development, mapped against key human factors and medical device design principles used throughout the process, is presented. The safety pack has si