Sample records for unresolved mechanistic issues

  1. CO activation pathways and the mechanism of Fischer–Tropsch synthesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ojeda, Manuel; Nabar, Rahul P.; Nilekar, Anand U.

    2010-06-15

    Unresolved mechanistic details of monomer formation in Fischer–Tropsch synthesis (FTS) and of its oxygen rejection routes are addressed here by combining kinetic and theoretical analyses of elementary steps on representative Fe and Co surfaces saturated with chemisorbed CO. These studies provide experimental and theoretical evidence for hydrogen-assisted CO activation as the predominant kinetically-relevant step on Fe and Co catalysts at conditions typical of FTS practice. H2 and CO kinetic effects on FTS rates and oxygen rejection selectivity (as H2O or CO2) and density functional theory estimates of activation barriers and binding energies are consistent with H-assisted CO dissociation, but notmore » with the previously accepted kinetic relevance of direct CO dissociation and chemisorbed carbon hydrogenation elementary steps. H-assisted CO dissociation removes O-atoms as H2O, while direct dissociation forms chemisorbed oxygen atoms that desorb as CO2. Direct CO dissociation routes are minor contributors to monomer formation on Fe and may become favored at high temperatures on alkali-promoted catalysts, but not on Co catalysts, which remove oxygen predominantly as H2O because of the preponderance of Hassisted CO dissociation routes. The merging of experiment and theory led to the clarification of persistent mechanistic issues previously unresolved by separate experimental and theoretical inquiries.« less

  2. Chemistry on the mesoscale: Modeling and measurement issues

    NASA Technical Reports Server (NTRS)

    Thompson, Anne; Pleim, John; Walcek, Christopher; Ching, Jason; Binkowski, Frank; Tao, Wei-Kuo; Dickerson, Russell; Pickering, Kenneth

    1993-01-01

    The topics covered include the following: Regional Acid Deposition Model (RADM) -- a coupled chemistry/mesoscale model; convection in RADM; unresolved issues for mesoscale modeling with chemistry -- nonprecipitating clouds; unresolved issues for mesoscale modeling with chemistry -- aerosols; tracer studies with Goddard Cumulus Ensemble Model (GCEM); field observations of trace gas transport in convection; and photochemical consequences of convection.

  3. Extrinsic and Intrinsic Motivation at 30: Unresolved Scientific Issues

    ERIC Educational Resources Information Center

    Reiss, Steven

    2005-01-01

    The undermining effect of extrinsic reward on intrinsic motivation remains unproven. The key unresolved issues are construct invalidity (all four definitions are unproved and two are illogical); measurement unreliability (the free-choice measure requires unreliable, subjective judgments to infer intrinsic motivation); inadequate experimental…

  4. Explicit Global Simulation of Gravity Waves up to the Lower Thermosphere

    NASA Astrophysics Data System (ADS)

    Becker, E.

    2016-12-01

    At least for short-term simulations, middle atmosphere general circulation models (GCMs) can be run with sufficiently high resolution in order to describe a good part of the gravity wave spectrum explicitly. Nevertheless, the parameterization of unresolved dynamical scales remains an issue, especially when the scales of parameterized gravity waves (GWs) and resolved GWs become comparable. In addition, turbulent diffusion must always be parameterized along with other subgrid-scale dynamics. A practical solution to the combined closure problem for GWs and turbulent diffusion is to dispense with a parameterization of GWs, apply a high spatial resolution, and to represent the unresolved scales by a macro-turbulent diffusion scheme that gives rise to wave damping in a self-consistent fashion. This is the approach of a few GCMs that extend from the surface to the lower thermosphere and simulate a realistic GW drag and summer-to-winter-pole residual circulation in the upper mesosphere. In this study we describe a new version of the Kuehlungsborn Mechanistic general Circulation Model (KMCM), which includes explicit (though idealized) computations of radiative transfer and the tropospheric moisture cycle. Particular emphasis is spent on 1) the turbulent diffusion scheme, 2) the attenuation of resolved GWs at critical levels, 3) the generation of GWs in the middle atmosphere from body forces, and 4) GW-tidal interactions (including the energy deposition of GWs and tides).

  5. National Technology Standards for K-12 Schools: A Case Study of Unresolved Issues in Public Relations

    ERIC Educational Resources Information Center

    Mullen, Carol A.; Kealy, William A.; Sullivan, Ashley

    2004-01-01

    This article addresses an important need--the dissemination of information relating to technology as a public relations tool--and the associated exigency for administrator and teacher technology training. Specifically, we identify the increased expectations for the performance of school leaders and teachers, as well as unresolved issues in public…

  6. Brain Networks for Working Memory and Factors of Intelligence Assessed in Males and Females with fMRI and DTI

    ERIC Educational Resources Information Center

    Tang, C. Y.; Eaves, E. L.; Ng, J. C.; Carpenter, D. M.; Mai, X.; Schroeder, D. H.; Condon, C. A.; Colom, R.; Haier, R. J.

    2010-01-01

    Neuro-imaging studies of intelligence implicate the importance of a parietal-frontal network. One unresolved issue is whether this network underlies a general factor of intelligence ("g") or other specific cognitive factors. A second unresolved issue is whether males and females use different parts of this network. Here we obtained intelligence…

  7. Wynoochee Hydropower/Fish Hatchery: Feasibility Report and Environmental Impact Statement.

    DTIC Science & Technology

    1982-09-30

    Unresolved Issues. There are no unresolved issues associated with the Wynoochee hydropower/fish hatchery plan. 4. Relationship to Environmental...Requirements.l/ The relationship of the Wynoochee hydropower/fish hatchery plan to environmental requirements is summarized in the following table...Implementation of the plan would I/The relationship of the satellite fish station to the environmental requirements is not included in this discussion. Compliance

  8. Interactive effects of body-size structure and adaptive foraging on food-web stability.

    PubMed

    Heckmann, Lotta; Drossel, Barbara; Brose, Ulrich; Guill, Christian

    2012-03-01

    Body-size structure of food webs and adaptive foraging of consumers are two of the dominant concepts of our understanding how natural ecosystems maintain their stability and diversity. The interplay of these two processes, however, is a critically important yet unresolved issue. To fill this gap in our knowledge of ecosystem stability, we investigate dynamic random and niche model food webs to evaluate the proportion of persistent species. We show that stronger body-size structures and faster adaptation stabilise these food webs. Body-size structures yield stabilising configurations of interaction strength distributions across food webs, and adaptive foraging emphasises links to resources closer to the base. Moreover, both mechanisms combined have a cumulative effect. Most importantly, unstructured random webs evolve via adaptive foraging into stable size-structured food webs. This offers a mechanistic explanation of how size structure adaptively emerges in complex food webs, thus building a novel bridge between these two important stabilising mechanisms. © 2012 Blackwell Publishing Ltd/CNRS.

  9. A rat model system to study complex disease risks, fitness, aging, and longevity.

    PubMed

    Koch, Lauren Gerard; Britton, Steven L; Wisløff, Ulrik

    2012-02-01

    The association between low exercise capacity and all-cause morbidity and mortality is statistically strong yet mechanistically unresolved. By connecting clinical observation with a theoretical base, we developed a working hypothesis that variation in capacity for oxygen metabolism is the central mechanistic determinant between disease and health (aerobic hypothesis). As an unbiased test, we show that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks, including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity. This contrasting animal model system may prove to be translationally superior relative to more widely used simplistic models for understanding geriatric biology and medicine. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Unresolved Childhood Sexual Abuse: Are Older Adults Affected?

    ERIC Educational Resources Information Center

    Allers, Christopher T.; And Others

    1992-01-01

    Presents case studies and discussions regarding 3 observed characteristics of unresolved childhood sexual abuse in adult survivors over 65 years of age. Specifically, chronic depression, elder abuse, and misdiagnosis of residual abuse trauma as dementia or mental illness are compared to parallel issues identified by researchers working with…

  11. Unfinished Business in Bereavement

    PubMed Central

    Klingspon, Kara L.; Holland, Jason M.; Neimeyer, Robert A.; Lichtenthal, Wendy G.

    2016-01-01

    Unfinished business (incomplete, unexpressed or unresolved relationship issues with the deceased) is frequently discussed as a risk factor for chronic and severe grief reactions. However, few empirical studies have examined this construct. The present study aimed to address this gap in the literature by examining the presence and severity of unfinished business as well as common themes of unfinished business reported in open-ended qualitative narratives among a sample of 224 bereaved individuals. In bivariate analyses, self-reported presence of unfinished business and the severity of distress due to unfinished business were both found to be associated with poorer bereavement outcomes. However, after controlling for potential confounds, distress related to unresolved issues with the deceased emerged as a more robust correlate of these outcomes. Qualitative responses were categorized, and the type of reported unfinished business was not significantly related to the degree of unfinished business distress or other bereavement outcomes. These findings provide preliminary justification for bereavement interventions that aim to ameliorate distress related to unresolved relational issues with the deceased. PMID:26057117

  12. Unfinished Business in Bereavement.

    PubMed

    Klingspon, Kara L; Holland, Jason M; Neimeyer, Robert A; Lichtenthal, Wendy G

    2015-01-01

    Unfinished business (incomplete, unexpressed or unresolved relationship issues with the deceased) is frequently discussed as a risk factor for chronic and severe grief reactions. However, few empirical studies have examined this construct. The present study aimed to address this gap in the literature by examining the presence and severity of unfinished business as well as common themes of unfinished business reported in open-ended qualitative narratives among a sample of 224 bereaved individuals. In bivariate analyses, self-reported presence of unfinished business and the severity of distress due to unfinished business were both found to be associated with poorer bereavement outcomes. However, after controlling for potential confounds, distress related to unresolved issues with the deceased emerged as a more robust correlate of these outcomes. Qualitative responses were categorized, and the type of reported unfinished business was not significantly related to the degree of unfinished business distress or other bereavement outcomes. These findings provide preliminary justification for bereavement interventions that aim to ameliorate distress related to unresolved relational issues with the deceased.

  13. Insect Phylogenomics: Exploring the Source of Incongruence Using New Transcriptomic Data

    PubMed Central

    Simon, Sabrina; Narechania, Apurva; DeSalle, Rob; Hadrys, Heike

    2012-01-01

    The evolution of the diverse insect lineages is one of the most fascinating issues in evolutionary biology. Despite extensive research in this area, the resolution of insect phylogeny especially of interordinal relationships has turned out to be still a great challenge. One of the challenges for insect systematics is the radiation of the polyneopteran lineages with several contradictory and/or unresolved relationships. Here, we provide the first transcriptomic data for three enigmatic polyneopteran orders (Dermaptera, Plecoptera, and Zoraptera) to clarify one of the most debated issues among higher insect systematics. We applied different approaches to generate 3 data sets comprising 78 species and 1,579 clusters of orthologous genes. Using these three matrices, we explored several key mechanistic problems of phylogenetic reconstruction including missing data, matrix selection, gene and taxa number/choice, and the biological function of the genes. Based on the first phylogenomic approach including these three ambiguous polyneopteran orders, we provide here conclusive support for monophyletic Polyneoptera, contesting the hypothesis of Zoraptera + Paraneoptera and Plecoptera + remaining Neoptera. In addition, we employ various approaches to evaluate data quality and highlight problematic nodes within the Insect Tree that still exist despite our phylogenomic approach. We further show how the support for these nodes or alternative hypotheses might depend on the taxon- and/or gene-sampling. PMID:23175716

  14. NATO and Hybrid Conflict: Unresolved Issues from the Past or Unresolvable Threats of the Present?

    DTIC Science & Technology

    2012-09-01

    order to strengthen the relationship between the UK and France, the Treaty of Dunkirk was signed in March 1947 expressing the Western European... Dunkirk Treaty was mainly a projection of European concerns about the reemergence of German aggression. The Rio Pact was more a representation of

  15. The Relationship between Psychological Well-Being and Perceived Wellness in Graduate-Level Counseling Students

    ERIC Educational Resources Information Center

    Harris, Michel; Martin, Magy; Martin, Don

    2013-01-01

    Research has established that individuals who provide personal therapy to others should have stable personal and professional lives, and possess a keen and accurate perception of wellness. Unfortunately, sometimes students pursuing careers in counseling and psychotherapy have unresolved psychological issues that, if unresolved, could later affect…

  16. Actin and Endocytosis in Budding Yeast

    PubMed Central

    Goode, Bruce L.; Eskin, Julian A.; Wendland, Beverly

    2015-01-01

    Endocytosis, the process whereby the plasma membrane invaginates to form vesicles, is essential for bringing many substances into the cell and for membrane turnover. The mechanism driving clathrin-mediated endocytosis (CME) involves > 50 different protein components assembling at a single location on the plasma membrane in a temporally ordered and hierarchal pathway. These proteins perform precisely choreographed steps that promote receptor recognition and clustering, membrane remodeling, and force-generating actin-filament assembly and turnover to drive membrane invagination and vesicle scission. Many critical aspects of the CME mechanism are conserved from yeast to mammals and were first elucidated in yeast, demonstrating that it is a powerful system for studying endocytosis. In this review, we describe our current mechanistic understanding of each step in the process of yeast CME, and the essential roles played by actin polymerization at these sites, while providing a historical perspective of how the landscape has changed since the preceding version of the YeastBook was published 17 years ago (1997). Finally, we discuss the key unresolved issues and where future studies might be headed. PMID:25657349

  17. Behavioural and physiological limits to vision in mammals

    PubMed Central

    Field, Greg D.

    2017-01-01

    Human vision is exquisitely sensitive—a dark-adapted observer is capable of reliably detecting the absorption of a few quanta of light. Such sensitivity requires that the sensory receptors of the retina, rod photoreceptors, generate a reliable signal when single photons are absorbed. In addition, the retina must be able to extract this information and relay it to higher visual centres under conditions where very few rods signal single-photon responses while the majority generate only noise. Critical to signal transmission are mechanistic optimizations within rods and their dedicated retinal circuits that enhance the discriminability of single-photon responses by mitigating photoreceptor and synaptic noise. We describe behavioural experiments over the past century that have led to the appreciation of high sensitivity near absolute visual threshold. We further consider mechanisms within rod photoreceptors and dedicated rod circuits that act to extract single-photon responses from cellular noise. We highlight how these studies have shaped our understanding of brain function and point out several unresolved questions in the processing of light near the visual threshold. This article is part of the themed issue ‘Vision in dim light’. PMID:28193817

  18. Impulse control disorders in Parkinson's disease: crossroads between neurology, psychiatry and neuroscience.

    PubMed

    Bugalho, Paulo; Oliveira-Maia, Albino J

    2013-01-01

    Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

  19. Studying Diversity in Teacher Education

    ERIC Educational Resources Information Center

    Ball, Arnetha, Ed.; Tyson, Cynthia A., Ed.

    2011-01-01

    "Studying Diversity in Teacher Education" is a collaborative effort by experts seeking to elucidate one of the most important issues facing education today. First, the volume examines historically persistent, yet unresolved issues in teacher education and presents research that is currently being done to address these issues. Second, it…

  20. Unresolved Technical Issues in Fair Interest Measurement.

    ERIC Educational Resources Information Center

    Cole, Nancy S.

    The problem of sex differences in interest measurement involves many technical issues and procedures. The purpose of this paper is to provide a description of the technical problems involved in construction, scoring, and interpretation of interest measures as related to sex differences and to suggest guidelines within these technical issues which…

  1. Problems and Issues of Diversity in the United States.

    ERIC Educational Resources Information Center

    Naylor, Larry L., Ed.

    A number of social problems created by cultural diversity in the United States seem to defy resolution. The essays in this collection address some of these issues and are designed to initiate serious discussions on some of the most serious questions. The chapters are: (1) "Introduction to American Cultural Diversity: Unresolved Questions, Issues,…

  2. Kohlberg and Gilligan: Duet or Duel?

    ERIC Educational Resources Information Center

    Jorgensen, Gunnar

    2006-01-01

    Most moral psychologists have come to accept two types of moral reasoning: Kohlberg's "justice" and Gilligan's "care", but there still seem to be some unresolved issues. By analysing and comparing Kohlberg's statement on some theoretical issues with some of Gilligan's statements in an interview in April 2003, I will look at some key issues in the…

  3. Psychological Constructivism in Therapy and Counseling: Some Unresolved Issues.

    ERIC Educational Resources Information Center

    Kruglanski, Arie W.

    1988-01-01

    Responds to Mahoney and Lyddon's review of constructivism in previous article by discussing several major problems that should be resolved if constructivism is to become widely accepted alternative to prevalent rationalist therapies. Included are issues of authority, pathology, and intervention. (NB)

  4. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.

    PubMed

    He, Xi C; Zhang, Jiwang; Tong, Wei-Gang; Tawfik, Ossama; Ross, Jason; Scoville, David H; Tian, Qiang; Zeng, Xin; He, Xi; Wiedemann, Leanne M; Mishina, Yuji; Li, Linheng

    2004-10-01

    In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.

  5. Extrinsic and intrinsic motivation at 30: Unresolved scientific issues.

    PubMed

    Reiss, Steven

    2005-01-01

    The undermining effect of extrinsic reward on intrinsic motivation remains unproven. The key unresolved issues are construct invalidity (all four definitions are unproved and two are illogical); measurement unreliability (the free-choice measure requires unreliable, subjective judgments to infer intrinsic motivation); inadequate experimental controls (negative affect and novelty, not cognitive evaluation, may explain "undermining" effects); and biased metareviews (studies with possible floor effects excluded, but those with possible ceiling effects included). Perhaps the greatest error with the undermining theory, however, is that it does not adequately recognize the multifaceted nature of intrinsic motivation (Reiss, 2004a). Advice to limit the use of applied behavior analysis based on "hidden" undermining effects is ideologically inspired and is unsupported by credible scientific evidence.

  6. Rational and Mechanistic Perspectives on Reinforcement Learning

    ERIC Educational Resources Information Center

    Chater, Nick

    2009-01-01

    This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: "mechanistic" and "rational." Reinforcement learning is often viewed in mechanistic terms--as…

  7. University Management Education and Research in Canada: Some Unresolved Issues.

    ERIC Educational Resources Information Center

    von Zur-Muehlen, Max

    An historical overview of university management education and research in Canada is presented and issues relevant to the present status of management education and research opportunities are discussed. Management and administrative studies schools in Canada receive, on the average, about four percent of the operating budget of the university…

  8. Forces Affecting Educational Decisions.

    ERIC Educational Resources Information Center

    Sullivan, Neil V.

    This speech begins with a discussion of broad social and political patterns and trends that are currently developing and continues to the specific unresolved social issues which will affect the nature and structure of educational systems. Those issues seen by the author is most likely to produce the greatest amount of activity are integration, the…

  9. The Challenges of Intersectionality: Researching Difference in Physical Education

    ERIC Educational Resources Information Center

    Flintoff, A.; Fitzgerald, H.; Scraton, S.

    2008-01-01

    Researching the intersection of class, race, gender, sexuality and disability raises many issues for educational research. Indeed, Maynard (2002, 33) has recently argued that "difference is one of the most significant, yet unresolved, issues for feminist and social thinking at the beginning of the twentieth century". This paper reviews…

  10. 14 CFR 431.37 - Mission readiness.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

  11. 14 CFR 431.37 - Mission readiness.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

  12. 14 CFR 431.37 - Mission readiness.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

  13. 14 CFR 431.37 - Mission readiness.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

  14. 14 CFR 431.37 - Mission readiness.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

  15. 15 CFR 971.300 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Certification of Applications § 971... the pending unresolved issues, the efforts to resolve them, and an estimate of the time required to do...

  16. Mathematical and Numerical Studies of Nonstandard Difference Equation Models of Differential Equations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mickens, Ronald E.

    2008-12-22

    This research examined the following items/issues: the NSFD methodology, technical achievements and applications, dissemination efforts and research related professional activities. Also a list of unresolved issues were identified that could form the basis for future research in the area of constructing and analyzing NSFD schemes for both ODE's and PDE's.

  17. Equity in Education: Opportunities and Challenges In A Changing Sri Lanka

    ERIC Educational Resources Information Center

    Sedere, Upali M.

    2010-01-01

    Equity is a major concern for all development actors. Although Sri Lanka has successfully addressed equity issues in education sector there are unresolved factors and variables those perpetuate inequity. There are emerging new equity issues those that Sri Lanka needs to address. The changing population dynamics and the huge middle class population…

  18. Unconscious Inhibition and Facilitation at the Objective Detection Threshold: Replicable and Qualitatively Different Unconscious Perceptual Effects

    ERIC Educational Resources Information Center

    Snodgrass, Michael; Shevrin, Howard

    2006-01-01

    Although the veridicality of unconscious perception is increasingly accepted, core issues remain unresolved [Jack, A., & Shallice, T. (2001). Introspective physicalism as an approach to the science of consciousness. "Cognition, 79," 161-196], and sharp disagreement persists regarding fundamental methodological and theoretical issues. The most…

  19. The Thermodynamics of Black Holes.

    PubMed

    Wald, Robert M

    2001-01-01

    We review the present status of black hole thermodynamics. Our review includes discussion of classical black hole thermodynamics, Hawking radiation from black holes, the generalized second law, and the issue of entropy bounds. A brief survey also is given of approaches to the calculation of black hole entropy. We conclude with a discussion of some unresolved open issues.

  20. 13 CFR 130.700 - Suspension, termination and non-renewal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the AA/SBDCs a written description of the unresolved issues, a summary of the positions of the District Office on the issues, and any supportive documentation. (5) The AA/SBDCs shall transmit a written... extension of time is mutually agreed upon by the recipient organization and the AA/SBDCs. (6) The AA/SBDCs...

  1. 13 CFR 130.700 - Suspension, termination and non-renewal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the AA/SBDCs a written description of the unresolved issues, a summary of the positions of the District Office on the issues, and any supportive documentation. (5) The AA/SBDCs shall transmit a written... extension of time is mutually agreed upon by the recipient organization and the AA/SBDCs. (6) The AA/SBDCs...

  2. 13 CFR 130.700 - Suspension, termination and non-renewal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the AA/SBDCs a written description of the unresolved issues, a summary of the positions of the District Office on the issues, and any supportive documentation. (5) The AA/SBDCs shall transmit a written... extension of time is mutually agreed upon by the recipient organization and the AA/SBDCs. (6) The AA/SBDCs...

  3. MicroRNAs in Honey Bee Caste Determination

    PubMed Central

    Ashby, Regan; Forêt, Sylvain; Searle, Iain; Maleszka, Ryszard

    2016-01-01

    The cellular mechanisms employed by some organisms to produce contrasting morphological and reproductive phenotypes from the same genome remains one of the key unresolved issues in biology. Honeybees (Apis mellifera) use differential feeding and a haplodiploid sex determination system to generate three distinct organismal outcomes from the same genome. Here we investigate the honeybee female and male caste-specific microRNA and transcriptomic molecular signatures during a critical time of larval development. Both previously undetected and novel miRNAs have been discovered, expanding the inventory of these genomic regulators in invertebrates. We show significant differences in the microRNA and transcriptional profiles of diploid females relative to haploid drone males as well as between reproductively distinct females (queens and workers). Queens and drones show gene enrichment in physio-metabolic pathways, whereas workers show enrichment in processes associated with neuronal development, cell signalling and caste biased structural differences. Interestingly, predicted miRNA targets are primarily associated with non-physio-metabolic genes, especially neuronal targets, suggesting a mechanistic disjunction from DNA methylation that regulates physio-metabolic processes. Accordingly, miRNA targets are under-represented in methylated genes. Our data show how a common set of genetic elements are differentially harnessed by an organism, which may provide the remarkable level of developmental flexibility required. PMID:26739502

  4. Emotion theory and research: highlights, unanswered questions, and emerging issues.

    PubMed

    Izard, Carroll E

    2009-01-01

    Emotion feeling is a phase of neurobiological activity, the key component of emotions and emotion-cognition interactions. Emotion schemas, the most frequently occurring emotion experiences, are dynamic emotion-cognition interactions that may consist of momentary/situational responding or enduring traits of personality that emerge over developmental time. Emotions play a critical role in the evolution of consciousness and the operations of all mental processes. Types of emotion relate differentially to types or levels of consciousness. Unbridled imagination and the ability for sympathetic regulation of empathy may represent both potential gains and losses from the evolution and ontogeny of emotion processes and consciousness. Unresolved issues include psychology's neglect of levels of consciousness that are distinct from access or reflective consciousness and use of the term "unconscious mind" as a dumpster for all mental processes that are considered unreportable. The relation of memes and the mirror neuron system to empathy, sympathy, and cultural influences on the development of socioemotional skills are unresolved issues destined to attract future research.

  5. Emotion Theory and Research: Highlights, Unanswered Questions, and Emerging Issues

    PubMed Central

    Izard, Carroll E.

    2009-01-01

    Emotion feeling is a phase of neurobiological activity, the key component of emotions and emotion-cognition interactions. Emotion schemas, the most frequently occurring emotion experiences, are dynamic emotion-cognition interactions that may consist of momentary/ situational responding or enduring traits of personality that emerge over developmental time. Emotions play a critical role in the evolution of consciousness and the operations of all mental processes. Types of emotion relate differentially to types or levels of consciousness. Unbridled imagination and the ability for sympathetic regulation of empathy may represent both potential gains and losses from the evolution and ontogeny of emotion processes and consciousness. Unresolved issues include psychology’s neglect of levels of consciousness that are distinct from access or reflective consciousness and use of the term “unconscious mind” as a dumpster for all mental processes that are considered unreportable. The relation of memes and the mirror neuron system to empathy, sympathy, and cultural influences on the development of socioemotional skills are unresolved issues destined to attract future research. PMID:18729725

  6. Expanding Horizons and Unresolved Conundrums: Language Testing and Assessment

    ERIC Educational Resources Information Center

    Leung, Constant; Lewkowicz, Jo

    2006-01-01

    Since the last "TESOL Quarterly" commemorative issue 15 years ago, there have been too many important developments in language testing and assessment for all of them to be discussed in a single article. Therefore, this article focuses on issues that we believe are integrally linked to pedagogic and curriculum concerns of English language teaching.…

  7. Crunch Seen on Ed. Issues after Election

    ERIC Educational Resources Information Center

    Klein, Alyson

    2012-01-01

    From the White House to Capitol Hill, the winners in this week's elections won't have much time to savor their victories. Even as federal policymakers sort out the political landscape, the remainder of 2012 and the early months of 2013 are likely to be dominated by divisive, unresolved issues with broad consequences for K-12 and higher…

  8. Sickle red cell adhesion: many issues and some answers.

    PubMed

    Kaul, D K

    2008-01-01

    Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

  9. Immunogenicity and immune tolerance coagulation Factors VIII and IX.

    PubMed

    Rup, B

    2003-01-01

    Some of the major issues related to the development and control of antibodies that occur during treatment of haemophilia with replacement factors (Factor VIII and Factor IX) are reviewed. Information on analytical issues, immunogenicity, and immune tolerance may be applicable to the study of other therapeutic proteins. Conversely, new information obtained from evaluation of other therapeutic protein products may address issues that remain unresolved for Factor VIII and FIX replacement therapy.

  10. Advance of Nitrogen Removal in Constructed Wetland

    NASA Astrophysics Data System (ADS)

    Xie, Anbin; Chen, Hao; You, Shaohong

    2018-01-01

    Based on current literature, the article reviewed the mechanism and route of nitrogen removal, discussed the microbial species associated with nitrogen metabolism in constructed wetlands. Key unresolved issues were concluded for classical and novel nitrogen removal routes.

  11. Preterm birth, an unresolved issue.

    PubMed

    Belizán, Jose M; Hofmeyr, Justus; Buekens, Pierre; Salaria, Natasha

    2013-11-15

    Premature birth is the world's leading cause of neonatal mortality with worldwide estimates indicating 11.1% of all live births were preterm in 2010. Preterm birth rates are increasing in most countries with continual differences in survival rates amongst rich and poor countries. Preterm birth is currently an important unresolved global issue with research efforts focusing on uterine quiescence and activation, the 'omics' approaches and implementation science in order to reduce the incidence and increase survival rates of preterm babies. The journal Reproductive Health has published a supplement entitled Born Too Soon which addresses factors in the preconception and pregnancy period which may increase the risk of preterm birth and also outlines potential interventions which may reduce preterm birth rates and improve survival of preterm babies by as much as 84% annually. This is critical in order to achieve the Millennium Development Goal (MDG 4) for child survival by 2015 and beyond.

  12. Confronting uncomfortable truths: receptivity and resistance to Aboriginal content in midwifery education.

    PubMed

    Thackrah, Rosalie D; Thompson, Sandra C

    2013-12-01

    The emotional responses of students undertaking a new, compulsory unit on Indigenous cultures and health were investigated as part of a broader study looking at culturally secure practice in midwifery education and service provision for Aboriginal women. Classroom observations were conducted on a first year midwifery cohort from July to October 2012 and students completed 'before and after' questionnaires. A spectrum of emotional responses was identified and found to be consistent with studies of medical student exposure to Aboriginal content. While stereotypes were challenged and perceptions altered as a result of the content, issues surrounding racism remained unresolved, with some students expressing dismay at the attitudes of their peers. This study confirmed the need for content on Aboriginal health and cultures to extend beyond one unit in a course. Learning and knowledge must be carefully integrated and developed to maximise understanding and ensure that unresolved issues are addressed.

  13. Oxytocin and the social brain: neural mechanisms and perspectives in human research.

    PubMed

    Kanat, Manuela; Heinrichs, Markus; Domes, Gregor

    2014-09-11

    The present paper summarizes functional imaging studies investigating the effects of intranasal oxytocin (OT) on brain responses to social stimuli. We aim to integrate previous research, point to unresolved issues and highlight perspectives for future studies. The studies so far have focused on identifying neural circuits underlying social information processing which are particularly sensitive to modulations by exogenous OT. Most consistently, stimulus-related responses of the amygdala and associated areas within the prefrontal and temporal cortices have been found to be modulated by OT administration. However, there are a number of unresolved issues related to the possible role of sex differences and hormonal status, genetic variability, and individual differences in socio-cognitive functioning. Future studies focusing on these open questions are expected to contribute to a more nuanced understanding of the role of the central OT system in humans and may provide the basis for novel treatment approaches for mental disorders characterized by social deficits. This article is part of a Special Issue entitled Oxytocin and Social Behav. © 2013 Published by Elsevier B.V.

  14. Safeguarding patient privacy in electronic healthcare in the USA: the legal view.

    PubMed

    Walsh, Diana; Passerini, Katia; Varshney, Upkar; Fjermestad, Jerry

    2008-01-01

    The conflict between the sweeping power of technology to access and assemble personal information and the ongoing concern about our privacy and security is ever increasing. While we gradually need higher electronic access to medical information, issues relating to patient privacy and reducing vulnerability to security breaches surmount. In this paper, we take a legal perspective and examine the existing patchwork of laws and obligations governing health information in the USA. The study finds that as Electronic Medical Records (EMRs) increase in scope and dissemination, privacy protections gradually decrease due to the shortcomings in the legal system. The contributions of this paper are (1) an overview of the legal EMR issues in the USA, and (2) the identification of the unresolved legal issues and how these will escalate when health information is transmitted over wireless networks. More specifically, the paper discusses federal and state government regulations such as the Electronic Communications Privacy Act, the Health Insurance Portability and Accountability Act (HIPAA) and judicial intervention. Based on the legal overview, the unresolved challenges are identified and suggestions for future research are included.

  15. Continuum and line spectra of degenerate dwarf X-ray sources

    NASA Technical Reports Server (NTRS)

    Lamb, D. Q.

    1981-01-01

    Recent observations of X-ray sources are summarized. Unresolved issues concerning these sources are discussed and an outline of the kinds of X-ray observations that would best advance the understanding of these sources is presented.

  16. Medicine's Library Lifeline.

    ERIC Educational Resources Information Center

    Shipman, Jean; Homan, Michael

    2003-01-01

    Discusses how librarians in the new role of "informationist" can help doctors and researches of medical information. Describes existing models of the informationist; potential benefits of working across professional boundaries outside the library; professional requirements; and unresolved issues for the new role, including potential…

  17. Artificial Intelligence for Command and Control

    DTIC Science & Technology

    1988-05-15

    complexity of information and are a very active current research area. Some of the important unresolved frame -related issues are control issues , such as...indepth analysis of the combat engineer’s decisio -mnaking activities. -Specificaly 3 combat engineers-stationed at Fort Bragg, North Carolina (307th...experience. The CETOOLS concept is potentially applicable in any decision- making environment, commercial or government, where plans for actions are

  18. 10 CFR 709.15 - Processing counterintelligence evaluation results.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Processing counterintelligence evaluation results. 709.15... and Protection of National Security § 709.15 Processing counterintelligence evaluation results. (a) If... are significant unresolved issues, not exclusively related to polygraph examination results...

  19. 10 CFR 709.15 - Processing counterintelligence evaluation results.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Processing counterintelligence evaluation results. 709.15... and Protection of National Security § 709.15 Processing counterintelligence evaluation results. (a) If... are significant unresolved issues, not exclusively related to polygraph examination results...

  20. 10 CFR 709.15 - Processing counterintelligence evaluation results.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Processing counterintelligence evaluation results. 709.15... and Protection of National Security § 709.15 Processing counterintelligence evaluation results. (a) If... are significant unresolved issues, not exclusively related to polygraph examination results...

  1. Scientific Results of the Nasa-sponsored Study Project on Mars: Evolution of Its Climate and Atmosphere

    NASA Technical Reports Server (NTRS)

    Clifford, Stephen M.; Greeley, Ronald; Haberle, Robert M.

    1988-01-01

    The scientific highlights of the Mars: Evolution of its Climate and Atmosphere (MECA) study project are reviewed and some of the important issues in Martian climate research that remain unresolved are discussed.

  2. Connecting active to passive fluorescence with photosynthesis: a method for evaluating remote sensing measurements of Chl fluorescence.

    PubMed

    Magney, Troy S; Frankenberg, Christian; Fisher, Joshua B; Sun, Ying; North, Gretchen B; Davis, Thomas S; Kornfeld, Ari; Siebke, Katharina

    2017-09-01

    Recent advances in the retrieval of Chl fluorescence from space using passive methods (solar-induced Chl fluorescence, SIF) promise improved mapping of plant photosynthesis globally. However, unresolved issues related to the spatial, spectral, and temporal dynamics of vegetation fluorescence complicate our ability to interpret SIF measurements. We developed an instrument to measure leaf-level gas exchange simultaneously with pulse-amplitude modulation (PAM) and spectrally resolved fluorescence over the same field of view - allowing us to investigate the relationships between active and passive fluorescence with photosynthesis. Strongly correlated, slope-dependent relationships were observed between measured spectra across all wavelengths (F λ , 670-850 nm) and PAM fluorescence parameters under a range of actinic light intensities (steady-state fluorescence yields, F t ) and saturation pulses (maximal fluorescence yields, F m ). Our results suggest that this method can accurately reproduce the full Chl emission spectra - capturing the spectral dynamics associated with changes in the yields of fluorescence, photochemical (ΦPSII), and nonphotochemical quenching (NPQ). We discuss how this method may establish a link between photosynthetic capacity and the mechanistic drivers of wavelength-specific fluorescence emission during changes in environmental conditions (light, temperature, humidity). Our emphasis is on future research directions linking spectral fluorescence to photosynthesis, ΦPSII, and NPQ. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  3. Mechanism of freeze-thaw injury and recovery: A cool retrospective and warming up to new ideas.

    PubMed

    Arora, Rajeev

    2018-05-01

    Understanding cellular mechanism(s) of freeze-thaw injury (FTI) is key to the efforts for improving plant freeze-tolerance by cultural methods or molecular/genetic approaches. However, not much work has been done in the last 25+ years to advance our understanding of the nature and cellular loci of FTI. Currently, two FTI lesions are predominantly implicated: 1) structural and functional perturbations in plasma membrane; 2) ROS-induced oxidative damage. While both have stood the test of time, many questions remain unresolved and other potentially significant lesions need to be investigated. Additionally, molecular mechanism of post-thaw recovery (PTR), a critical component of frost-survival, has not been well investigated. Mechanistic understanding of repair after reversible injury could expand the options for strategies to improve frost-hardiness. In this review, without claiming to be exhaustive, I have attempted to synthesize major discoveries from last several decades on the mechanisms of FTI and the relatively little research conducted thus far on PTR mechanisms. It is followed by proposing of hypotheses for mechanism(s) for irreversible FTI or PTR involving cytosolic calcium and ROS signaling. Perspective is presented on some unresolved questions and research on new ideas to fill the knowledge gaps and advance the field. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Frost for the trees: Did climate increase erosion in unglaciated landscapes during the late Pleistocene?

    PubMed

    Marshall, Jill A; Roering, Joshua J; Bartlein, Patrick J; Gavin, Daniel G; Granger, Darryl E; Rempel, Alan W; Praskievicz, Sarah J; Hales, Tristram C

    2015-11-01

    Understanding climatic influences on the rates and mechanisms of landscape erosion is an unresolved problem in Earth science that is important for quantifying soil formation rates, sediment and solute fluxes to oceans, and atmospheric CO2 regulation by silicate weathering. Glaciated landscapes record the erosional legacy of glacial intervals through moraine deposits and U-shaped valleys, whereas more widespread unglaciated hillslopes and rivers lack obvious climate signatures, hampering mechanistic theory for how climate sets fluxes and form. Today, periglacial processes in high-elevation settings promote vigorous bedrock-to-regolith conversion and regolith transport, but the extent to which frost processes shaped vast swaths of low- to moderate-elevation terrain during past climate regimes is not well established. By combining a mechanistic frost weathering model with a regional Last Glacial Maximum (LGM) climate reconstruction derived from a paleo-Earth System Model, paleovegetation data, and a paleoerosion archive, we propose that frost-driven sediment production was pervasive during the LGM in our unglaciated Pacific Northwest study site, coincident with a 2.5 times increase in erosion relative to modern rates. Our findings provide a novel framework to quantify how climate modulates sediment production over glacial-interglacial cycles in mid-latitude unglaciated terrain.

  5. MODIFYING THE AVIAN REPRODUCTION TEST GUIDELINES FOR DETERMINING DOSE-RESPONSE RELATIONSHIPS

    EPA Science Inventory

    As a subgroup of the OECD Expert Group on Assessment of Endocrine Disrupting Effects in Birds, we reviewed unresolved methodological issues important for the development of a two-generation toxicity text, discussed advantages and disadvantages of alternative approaches, and propo...

  6. World-View Entrapment: Moral-Ethical Implications for Gifted Education.

    ERIC Educational Resources Information Center

    Ambrose, Don

    2000-01-01

    This article explores the moral-ethical implications of the mechanistic world view and related issues such as technological determinism, social Darwinism, and androcentrism. It finds that educational approaches reinforced by the mechanistic world view include positivistic approaches to curriculum, instruction, and research. Recommendations for…

  7. Manipulating Color and Other Visual Information Influences Picture Naming at Different Levels of Processing: Evidence from Alzheimer Subjects and Normal Controls

    ERIC Educational Resources Information Center

    Zannino, Gian Daniele; Perri, Roberta; Salamone, Giovanna; Di Lorenzo, Concetta; Caltagirone, Carlo; Carlesimo, Giovanni A.

    2010-01-01

    There is now a large body of evidence suggesting that color and photographic detail exert an effect on recognition of visually presented familiar objects. However, an unresolved issue is whether these factors act at the visual, the semantic or lexical level of the recognition process. In the present study, we investigated this issue by having…

  8. ISSUES IN DEVELOPING A TWO-GENERATION AVIAN TOXICITY TEST WITH JAPANESE QUAIL

    EPA Science Inventory

    As a subgroup of the OECD Expert Group on Assessment of Endocrine Disrupting Effects in Birds, we reviewed unresolved methodological issures important for the development of a two-generation toxicity test, discussed advantages and disadvantages of alternative approaches, and prop...

  9. Research projects lead by the USDA Cranberry Entomology Laboratory (CEL)

    USDA-ARS?s Scientific Manuscript database

    1. Newly discovered native nematode species represent bio-insecticides (grad student project) a. Problems being addressed: Issues over flea beetle control; unresolved questions over pesticide use during bloom. b. Discoveries: at least two native nematodes species new to science have been discovered ...

  10. Planetary science and resource utilization at a lunar outpost - Chemical analytical facility requirements

    NASA Technical Reports Server (NTRS)

    Taylor, Lawrence A.

    1992-01-01

    Unresolved issues of lunar geology are reviewed and the role of a lunar outpost in helping to address them is considered. Plans for in situ resource utilization of lunar materials are examined. Concepts for a lunar outpost are described.

  11. 7 CFR 1940.307 - Environmental responsibilities within the State Office.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... any unresolved or difficult environmental issues in a timely manner; and (3) Incorporate into projects... 7 Agriculture 13 2010-01-01 2009-01-01 true Environmental responsibilities within the State Office..., DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program § 1940...

  12. Delivery Issues in the Day Care Debate. Occasional Papers in Education: Paper No. 2 - Policy Studies of the Early Childhood Planning Project.

    ERIC Educational Resources Information Center

    McGee, Maureen

    The question of who should provide day care services is an unresolved issue in the current day care debate and a topic now on the national agenda because it is the common concern of a constellation of diverse, highly motivated interest groups. Motivation for extending day care in the United States stems from several factors: among these are the…

  13. Space station human productivity study. Volume 4: Issues

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The 305 Issues contained represent topics recommended for study in order to develop requirements in support of space station crew performance/productivity. The overall subject matter, space station elements affecting crew productivity, was organized into a coded subelement listing, which is included for the reader's reference. Each issue is numbered according to the 5-digit topical coding scheme. The requirements column on each Issue page shows a cross-reference to the unresolved requirement statement(s). Because topical overlaps were frequently encountered, many initial Issues were consolidated. Apparent gaps, therefore, may be accounted for by an Issue described within a related subelement. A glossary of abbreviations used throughout the study documentation is also included.

  14. Molecular Phylogenetics and the Perennial Problem of Homology.

    PubMed

    Inkpen, S Andrew; Doolittle, W Ford

    2016-12-01

    The concept of homology has a long history, during much of which the issue has been how to reconcile similarity and common descent when these are not coextensive. Although thinking molecular phylogeneticists have learned not to say "percent homology," the problems are deeper than that and unresolved.

  15. The NII and the New World Trade Agreement.

    ERIC Educational Resources Information Center

    Smoot, Oliver

    1994-01-01

    Examines the relationship between the National Information Infrastructure (NII) and the new General Agreement on Tariffs and Trade. Topics discussed include the reduction or elimination of tariffs on NII products; protection of copyrighted works; unresolved trade issues, including the European telecommunications market; standards; and privacy and…

  16. Uterine influences on conceptus development in fertility-classified heifers

    USDA-ARS?s Scientific Manuscript database

    A major unresolved issue is how the uterus influences infertility and subfertility in cattle. Serial embryo transfer was previously used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). To assess pregnancy loss in those animals, two in vivo produced embryos were transfer...

  17. Behavioral Assessment and Interventions in Youth Sports.

    ERIC Educational Resources Information Center

    Smith, Ronald E.; And Others

    1996-01-01

    Discusses the use of behavioral assessment for both descriptive and program evaluation purposes. Notes the use of behavioral assessment to study coaching behaviors and their effects on young athletes. Operant and cognitive-behavioral interventions have proven effective in both athletic and psychosocial outcomes. Discusses unresolved issues and…

  18. Poetry as a Healing Experience for Teams.

    ERIC Educational Resources Information Center

    Bronson, Jim; Schaub, Nancy

    Experiential practitioners have the opportunity to help groups move to a higher level of functioning, getting beyond unresolved emotional issues and becoming more truthful, immediate, involved, and collaborative. This critical process takes place along a continuum from "staying safe and shallow" at one end to "going deep and…

  19. Bullying by Definition: An Examination of Definitional Components of Bullying

    ERIC Educational Resources Information Center

    Goldsmid, Susan; Howie, Pauline

    2014-01-01

    Lack of definitional consensus remains an important unresolved issue within bullying research. This study examined the ability of definitional variables to predict overall level of victimisation (distress, power inequity, and provocation as predictors) and bullying (intention to harm, power inequity, and provocation as predictors) in 246…

  20. Structured Ethical Reflection in Practitioner Inquiry: Theory, Pedagogy, and Practice

    ERIC Educational Resources Information Center

    Stevens, Douglas M.; Brydon-Miller, Mary; Raider-Roth, Miriam

    2016-01-01

    Practitioner inquiry provides a powerful tool for improving practice and addressing critical issues in classrooms, schools, and broader communities. However, it also raises unique ethical challenges that often go unrecognized and unresolved. Structured Ethical Reflection (SER) provides teacher researchers with a process for identifying core values…

  1. Determination of Passing Scores on Certification Examinations: An Unresolved Issue.

    ERIC Educational Resources Information Center

    Karni, Karen R.; Lofsness, Karen G.

    1985-01-01

    This study examined the results obtained from certification applicants and practitioners on a national certification examination for clinical laboratory scientists (medical technologists), using a modified Angoff procedure to establish the cut-off score. The major question of the investigation concerned whether the cut-off score was appropriate.…

  2. Student Personnel Administration and the Adult Learner: An Unresolved Issue.

    ERIC Educational Resources Information Center

    Watson, Rollin J.

    The role of college student personnel administration in serving adult learners is considered. Historical trends in the student personnel function and the philosophy that student personnel workers are educators who create programs that contribute to the student's overall educational growth are examined. Changes for the student development personnel…

  3. 12 CFR 5.34 - Operating subsidiaries.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... entity if: (A) The bank has the ability to control the management and operations of the subsidiary; (B... entity is a corporation, limited liability company, or limited partnership; and (3) The bank: (i) Has the... analysis if the proposal is novel, unusually complex, or raises substantial unresolved legal issues. In...

  4. 12 CFR 5.34 - Operating subsidiaries.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... entity if: (A) The bank has the ability to control the management and operations of the subsidiary; (B... entity is a corporation, limited liability company, or limited partnership; and (3) The bank: (i) Has the... analysis if the proposal is novel, unusually complex, or raises substantial unresolved legal issues. In...

  5. 12 CFR 5.34 - Operating subsidiaries.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... entity if: (A) The bank has the ability to control the management and operations of the subsidiary; (B... entity is a corporation, limited liability company, or limited partnership; and (3) The bank: (i) Has the... analysis if the proposal is novel, unusually complex, or raises substantial unresolved legal issues. In...

  6. Mode(s) of action of arsenic-induced tumors and toxicity.

    EPA Science Inventory

    Although arsenic has long been known for its toxicity and carcinogenicity, it is unknown exactly how these adverse health effects ocurr. Three of the biggest unresolved issues in arsenic exposures and adverse health effects are (a) what is (are) the mode of action (MOA)(s) of ar...

  7. Accounting for sub-pixel variability of clouds and/or unresolved spectral variability, as needed, with generalized radiative transfer theory

    DOE PAGES

    Davis, Anthony B.; Xu, Feng; Collins, William D.

    2015-03-01

    Atmospheric hyperspectral VNIR sensing struggles with sub-pixel variability of clouds and limited spectral resolution mixing molecular lines. Our generalized radiative transfer model addresses both issues with new propagation kernels characterized by power-law decay in space.

  8. Brain Responses to Filled Gaps

    ERIC Educational Resources Information Center

    Hestvik, Arild; Maxfield, Nathan; Schwartz, Richard G.; Shafer, Valerie

    2007-01-01

    An unresolved issue in the study of sentence comprehension is whether the process of gap-filling is mediated by the construction of empty categories (traces), or whether the parser relates fillers directly to the associated verb's argument structure. We conducted an event-related potentials (ERP) study that used the violation paradigm to examine…

  9. Androgyny as Trait and as Role: Unresolved Issues.

    ERIC Educational Resources Information Center

    Spence, Janet T.

    In the late 1970's androgyny as a concept gained respectability, accompanied, however, by a backlash. Debate centered primarily on scientific grounds and both sides failed to define the concepts of masculinity, femininity and androgyny, including possible cultural relativity. Most empirical research on androgyny uses either the BSRI or the PAQ…

  10. Sexuality and the Curriculum: The Politics and Practices of Sexuality Education. Critical Issues in the Curriculum.

    ERIC Educational Resources Information Center

    Sears, James T., Ed.

    This book of essays explores the explicit and hidden curriculum of sexuality from kindergarten through college. The 15 interrelated essays challenge conventional assumptions regarding sexuality and the curriculum by applying non-traditional perspectives to traditionally unresolved problems while proposing specific curricular strategies and…

  11. Traumatic Brain Injury and Vocational Rehabilitation.

    ERIC Educational Resources Information Center

    Corthell, David W., Ed.

    Intended to serve as a resource guide on traumatic brain injury for rehabilitation practitioners, the book's 10 chapters are grouped into sections which provide an introduction and examine aspects of evaluation, treatment and placement planning, and unresolved issues. Chapters have the following titles and authors: "Scope of the Problem" (Marilyn…

  12. "My Mom and Her Boyfriend Fuss": A Five-Minute RAP

    ERIC Educational Resources Information Center

    Laursen, Erik K.; Whindleton, Kendra

    2012-01-01

    Unresolved issues from home often spill over into behavior problems at school. This article discusses the five-minute RAP techniques: (1) connect; (2) clarify; and (3) restore. The authors present a case study wherein this brief restorative intervention had been a successful alternative to punishment and exclusion.

  13. The future of microarray technology: networking the genome search.

    PubMed

    D'Ambrosio, C; Gatta, L; Bonini, S

    2005-10-01

    In recent years microarray technology has been increasingly used in both basic and clinical research, providing substantial information for a better understanding of genome-environment interactions responsible for diseases, as well as for their diagnosis and treatment. However, in genomic research using microarray technology there are several unresolved issues, including scientific, ethical and legal issues. Networks of excellence like GA(2)LEN may represent the best approach for teaching, cost reduction, data repositories, and functional studies implementation.

  14. Biotechnology patent challenged: ex-colleague seeks share of the credit.

    PubMed

    Budiansky, Stephen

    1982-11-25

    Dr. Robert Helling, supported by the University of Michigan, has decided to press a claim to co-ownership of two Cohen-Boyer genetic engineering patents assigned to Stanford and the University of California. This decision will likely delay further the issuing of the second patent, tentatively rejected by the Patent Office in part on the basis of Helling's unresolved role. It may also increase pressure for a re-examination of the first patent issued in 1980.

  15. Frost for the trees: Did climate increase erosion in unglaciated landscapes during the late Pleistocene?

    PubMed Central

    Marshall, Jill A.; Roering, Joshua J.; Bartlein, Patrick J.; Gavin, Daniel G.; Granger, Darryl E.; Rempel, Alan W.; Praskievicz, Sarah J.; Hales, Tristram C.

    2015-01-01

    Understanding climatic influences on the rates and mechanisms of landscape erosion is an unresolved problem in Earth science that is important for quantifying soil formation rates, sediment and solute fluxes to oceans, and atmospheric CO2 regulation by silicate weathering. Glaciated landscapes record the erosional legacy of glacial intervals through moraine deposits and U-shaped valleys, whereas more widespread unglaciated hillslopes and rivers lack obvious climate signatures, hampering mechanistic theory for how climate sets fluxes and form. Today, periglacial processes in high-elevation settings promote vigorous bedrock-to-regolith conversion and regolith transport, but the extent to which frost processes shaped vast swaths of low- to moderate-elevation terrain during past climate regimes is not well established. By combining a mechanistic frost weathering model with a regional Last Glacial Maximum (LGM) climate reconstruction derived from a paleo-Earth System Model, paleovegetation data, and a paleoerosion archive, we propose that frost-driven sediment production was pervasive during the LGM in our unglaciated Pacific Northwest study site, coincident with a 2.5 times increase in erosion relative to modern rates. Our findings provide a novel framework to quantify how climate modulates sediment production over glacial-interglacial cycles in mid-latitude unglaciated terrain. PMID:26702434

  16. The genetic basis of a plant–insect coevolutionary key innovation

    PubMed Central

    Wheat, Christopher W.; Vogel, Heiko; Wittstock, Ute; Braby, Michael F.; Underwood, Dessie; Mitchell-Olds, Thomas

    2007-01-01

    Ehrlich and Raven formally introduced the concept of stepwise coevolution using butterfly and angiosperm interactions in an attempt to account for the impressive biological diversity of these groups. However, many biologists currently envision butterflies evolving 50 to 30 million years (Myr) after the major angiosperm radiation and thus reject coevolutionary origins of butterfly biodiversity. The unresolved central tenet of Ehrlich and Raven's theory is that evolution of plant chemical defenses is followed closely by biochemical adaptation in insect herbivores, and that newly evolved detoxification mechanisms result in adaptive radiation of herbivore lineages. Using one of their original butterfly-host plant systems, the Pieridae, we identify a pierid glucosinolate detoxification mechanism, nitrile-specifier protein (NSP), as a key innovation. Larval NSP activity matches the distribution of glucosinolate in their host plants. Moreover, by using five different temporal estimates, NSP seems to have evolved shortly after the evolution of the host plant group (Brassicales) (≈10 Myr). An adaptive radiation of these glucosinolate-feeding Pierinae followed, resulting in significantly elevated species numbers compared with related clades. Mechanistic understanding in its proper historical context documents more ancient and dynamic plant–insect interactions than previously envisioned. Moreover, these mechanistic insights provide the tools for detailed molecular studies of coevolution from both the plant and insect perspectives. PMID:18077380

  17. Work–Family Conflict and Health Among Working Parents: Potential Linkages for Family Studies and Social Neuroscience

    PubMed Central

    Grzywacz, Joseph G.; Smith, Amy M.

    2016-01-01

    In this paired article the authors review research on paid work, parenting, and health in order to isolate fundamental questions and issues that remain unaddressed. Next, consistent with the theme of this special issue, the authors introduce social neuroscience and highlight how this emerging multidisciplinary science offers substantial promise for advancing key unresolved issues in the paid work, parenting, and health literature. The article concludes with suggestions for promising areas of research wherein family scientists and social neuroscientists could build collaborative research to address gaps in the work–family literature. PMID:27840467

  18. Collins Center Update. Volume 15, Issue 3. April-June 2013

    DTIC Science & Technology

    2013-06-01

    and unresolved boundary issues with Mali, Niger , and Benin . Within this security environment the Burkinabe Armed Forces are working with the U.S...Analytical Exchanges at Collins Hall • Burkina Faso Military Strategy Review Phase II • Joint Land, Air and Sea Strategic Exercise (JLASS-EX) 2013...Prescribed by ANSI Std Z39-18 2 C S L D Burkina Faso Military Strategy Review Phase II Prof. B.F. Griffard and Prof. Bert B. Tussing Center for Strategic

  19. Accountability as a Way Forward for Privacy Protection in the Cloud

    NASA Astrophysics Data System (ADS)

    Pearson, Siani; Charlesworth, Andrew

    The issue of how to provide appropriate privacy protection for cloud computing is important, and as yet unresolved. In this paper we propose an approach in which procedural and technical solutions are co-designed to demonstrate accountability as a path forward to resolving jurisdictional privacy and security risks within the cloud.

  20. Contextual E-Learning Evaluation: A Preliminary Framework

    ERIC Educational Resources Information Center

    Voigt, Christian; Swatman, Paula M. C.

    2004-01-01

    The evaluation of solutions is a major unresolved issue for all those involved in e-learning. In this paper we illustrate the importance of context by means of a qualitative comparison of two e-learning prototype implementations--an action research case undertaken in conjunction with a major German insurance company; and a more experimental…

  1. Iterative Purification and Effect Size Use with Logistic Regression for Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    French, Brian F.; Maller, Susan J.

    2007-01-01

    Two unresolved implementation issues with logistic regression (LR) for differential item functioning (DIF) detection include ability purification and effect size use. Purification is suggested to control inaccuracies in DIF detection as a result of DIF items in the ability estimate. Additionally, effect size use may be beneficial in controlling…

  2. Franchise competition in the electric utility industry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vince, C.A.; Fogel, J.C.

    Franchise competition is - and should be - an integral part of enhanced competition. It serves the traditional goal of encouraging lower costs through the threat of takeover or purchase. However, the issue of utility recovery for stranded costs stands as a major unresolved question affecting customers` ability to partake of this central aspect of competition.

  3. Special Education History, Current Status and Future: India

    ERIC Educational Resources Information Center

    Antony, Pavan John

    2013-01-01

    Education of all children in public schools, including those with disabilities, continues to be an unresolved issue in many countries around the globe. While education of all children is mandated by law and considered a basic human right in many countries, the current status of implementation varies. India, for example, is an ancient country that…

  4. Framing and Assessing Classroom Opportunity to Learn: The Case of Mexico

    ERIC Educational Resources Information Center

    Jensen, Bryant; Pérez Martínez, María Guadalupe; Aguilar Escobar, Angélica

    2016-01-01

    Educational policy in Mexico and throughout Latin America is shifting focus from school access to school quality. Improving "quality" is often interpreted as enhancing student learning opportunities, but three issues remain unresolved: (a) what constitutes opportunity to learn (OTL) in classrooms; (b) how to assess classroom OTL (COTL);…

  5. Collaborative Reasoning: Language-Rich Discussions for English Learners

    ERIC Educational Resources Information Center

    Zhang, Jie; Dougherty Stahl, Katherine A.

    2012-01-01

    Collaborative Reasoning (CR) is a peer-led, small group discussion approach that aims to promote intellectual and personal engagement in elementary school classrooms. In CR, students read a text that raises an unresolved issue with multiple and competing points of view. Students are expected to take positions on a big question, support the…

  6. When Others' Performance Just Isn't Good Enough: Educational Leaders' Framing of Concerns in Private and Public

    ERIC Educational Resources Information Center

    Sinnema, Claire E. L.; Le Fevre, Deidre; Robinson, Viviane M. J.; Pope, Denyse

    2013-01-01

    Effective instructional leadership demands that leaders address the inevitable problems and concerns that exist in any educational organization. Unfortunately, much evidence suggests that many important concerns, including teacher performance issues, continue to be unaddressed and unresolved. This article portrays the nature of concerns facing 77…

  7. The giant panda gut microbiome.

    PubMed

    Wei, Fuwen; Wang, Xiao; Wu, Qi

    2015-08-01

    Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Idiosyncratic Genetic Specificity for Neurolinguistic Systems: A Cause of Atypical or Delayed Language Acquisition.

    ERIC Educational Resources Information Center

    Lamendella, John T.

    The diagnostic problem presented by children without obvious neurological, cognitive, genetic, emotional or environmental basis for their atypical or delayed language development is discussed. One unresolved issue is whether the deficits of such dysphasic children are linguistic or are more fundamental cognitive or perceptuomotor deficits. A…

  9. The Role of Broca's Area in Sentence Comprehension

    ERIC Educational Resources Information Center

    Rogalsky, Corianne; Hickok, Gregory

    2011-01-01

    The role of Broca's area in sentence processing has been debated for the last 30 years. A central and still unresolved issue is whether Broca's area plays a specific role in some aspect of syntactic processing (e.g., syntactic movement, hierarchical structure building) or whether it serves a more general function on which sentence processing…

  10. Learning How They Learn: A Review of the Literature on Learning Styles.

    ERIC Educational Resources Information Center

    Wilson, Vicki A.

    The literature on learning styles is full of unresolved issues, both theoretical and practical. Early research into learning styles includes that of H. A. Witkin, who developed the Embedded Figures Test in the late 1960s. This test determines the "field dependence" or "field independence" of individuals, marking their global…

  11. Widening Access to Scottish Higher Education: Unresolved Issues and Future Challenges

    ERIC Educational Resources Information Center

    Riddell, Sheila

    2016-01-01

    Despite the Scottish Government's frequent affirmation of its commitment to social justice principles, there has of late been a recognition of the need for firmer action to tackle the social class gap in higher education participation, reflecting wider social inequalities in Scotland. In a recent policy statement, Angela Constance, Cabinet…

  12. Causal Indicator Models: Unresolved Issues of Construction and Evaluation

    ERIC Educational Resources Information Center

    West, Stephen G.; Grimm, Kevin J.

    2014-01-01

    These authors agree with Bainter and Bollen that causal effects represents a useful measurement structure in some applications. The structure of the science of the measurement problem should determine the model; the measurement model should not determine the science. They also applaud Bainter and Bollen's important reminder that the full…

  13. The Influence of Management on the Cost of Fire Protection

    ERIC Educational Resources Information Center

    Donahue, Amy K.

    2004-01-01

    An important and unresolved issue central to the study of government performance is how the actions of managers and the nature of organizations affect the cost of public services. This paper presents an empirical analysis of fire departments that estimates the influence of managerial choices on per capita spending within a simultaneous public…

  14. Chocolate and cardiovascular health: is it too good to be true?

    PubMed

    Ariefdjohan, Merlin W; Savaiano, Dennis A

    2005-12-01

    Recent findings indicate that cocoa and chocolate, when processed appropriately, may contain relatively large amounts of flavonoids, particularly catechin and epicatechin. We review the benefits of these flavonoids, specifically with regard to cardiovascular health, and raise several unresolved issues that suggest the need for additional research and product development in this area.

  15. Risk Management: the Economics and Mor ality of Safety Revisited

    NASA Astrophysics Data System (ADS)

    Adams, John

    The introduction to the proceedings of the Royal Academy of Engineering 2006 seminar on The Economics and Morality of Safety (RAEng 2006) concluded with a list of issues that were ‘worthy of further exploration’. I have reduced them to the following questions: Why do moral arguments about ‘rights’ persist unresolved?

  16. Rational and mechanistic perspectives on reinforcement learning.

    PubMed

    Chater, Nick

    2009-12-01

    This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: mechanistic and rational. Reinforcement learning is often viewed in mechanistic terms--as describing the operation of aspects of an agent's cognitive and neural machinery. Yet it can also be viewed as a rational level of description, specifically, as describing a class of methods for learning from experience, using minimal background knowledge. This paper considers how rational and mechanistic perspectives differ, and what types of evidence distinguish between them. Reinforcement learning research in the cognitive and brain sciences is often implicitly committed to the mechanistic interpretation. Here the opposite view is put forward: that accounts of reinforcement learning should apply at the rational level, unless there is strong evidence for a mechanistic interpretation. Implications of this viewpoint for reinforcement-based theories in the cognitive and brain sciences are discussed.

  17. Golgi Membrane Dynamics Viewed Through a Lens of Lipids

    PubMed Central

    Bankaitis, Vytas A.; Garcia-Mata, Rafael; Mousley, Carl J.

    2012-01-01

    Summary The striking morphology of the Golgi complex has fascinated cell biologists since its discovery over 100 years ago. Yet, despite intense efforts to understand how membrane flow relates to Golgi form and function, this organelle continues to baffle cell biologists and biochemists alike. Fundamental questions regarding Golgi function, while hotly debated, remain unresolved. While Golgi function is historically described from a protein-centric point of view, we now appreciate that conceptual frameworks for how lipid metabolism is integrated with Golgi biogenesis and function are essential for a mechanistic understanding of this fascinating organelle. It is from a lipid-centric perspective that we discuss the larger question of Golgi dynamics and membrane trafficking. We review the growing body of evidence for how lipid metabolism is integrally written into the engineering of the Golgi system, and highlight questions for future study. PMID:22625862

  18. Cytokine-Mediated Loss of Blood Dendritic Cells During Epstein-Barr Virus-Associated Acute Infectious Mononucleosis: Implication for Immune Dysregulation.

    PubMed

    Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

    2015-12-15

    Acute infectious mononucleosis (IM) is associated with altered expression of inflammatory cytokines and disturbed T-cell homeostasis, however, the precise mechanism of this immune dysregulation remains unresolved. In the current study we demonstrated a significant loss of circulating myeloid and plasmacytoid dendritic cells (DCs) during acute IM, a loss correlated with the severity of clinical symptoms. In vitro exposure of blood DCs to acute IM plasma resulted in loss of plasmacytoid DCs, and further studies with individual cytokines showed that exposure to interleukin 10 could replicate this effect. Our data provide important mechanistic insight into dysregulated immune homeostasis during acute IM. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Computational modeling of neurostimulation in brain diseases.

    PubMed

    Wang, Yujiang; Hutchings, Frances; Kaiser, Marcus

    2015-01-01

    Neurostimulation as a therapeutic tool has been developed and used for a range of different diseases such as Parkinson's disease, epilepsy, and migraine. However, it is not known why the efficacy of the stimulation varies dramatically across patients or why some patients suffer from severe side effects. This is largely due to the lack of mechanistic understanding of neurostimulation. Hence, theoretical computational approaches to address this issue are in demand. This chapter provides a review of mechanistic computational modeling of brain stimulation. In particular, we will focus on brain diseases, where mechanistic models (e.g., neural population models or detailed neuronal models) have been used to bridge the gap between cellular-level processes of affected neural circuits and the symptomatic expression of disease dynamics. We show how such models have been, and can be, used to investigate the effects of neurostimulation in the diseased brain. We argue that these models are crucial for the mechanistic understanding of the effect of stimulation, allowing for a rational design of stimulation protocols. Based on mechanistic models, we argue that the development of closed-loop stimulation is essential in order to avoid inference with healthy ongoing brain activity. Furthermore, patient-specific data, such as neuroanatomic information and connectivity profiles obtainable from neuroimaging, can be readily incorporated to address the clinical issue of variability in efficacy between subjects. We conclude that mechanistic computational models can and should play a key role in the rational design of effective, fully integrated, patient-specific therapeutic brain stimulation. © 2015 Elsevier B.V. All rights reserved.

  20. Cognitive science as an interface between rational and mechanistic explanation.

    PubMed

    Chater, Nick

    2014-04-01

    Cognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation--as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces. Copyright © 2014 Cognitive Science Society, Inc.

  1. Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

    PubMed Central

    Jinot, Jennifer; Scott, Cheryl Siegel; Makris, Susan L.; Cooper, Glinda S.; Dzubow, Rebecca C.; Bale, Ambuja S.; Evans, Marina V.; Guyton, Kathryn Z.; Keshava, Nagalakshmi; Lipscomb, John C.; Barone, Stanley; Fox, John F.; Gwinn, Maureen R.; Schaum, John; Caldwell, Jane C.

    2012-01-01

    Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. Objectives: We summarized the key findings and scientific issues regarding the human health effects of TCE in the U.S. EPA’s toxicological review. Methods: In this assessment we synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. Discussion: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data strongly supported the conclusions that TCE causes kidney cancer in humans and that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in developmental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. Conclusions: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for noncancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus. PMID:23249866

  2. Memory Retrieval Given Two Independent Cues: Cue Selection or Parallel Access?

    ERIC Educational Resources Information Center

    Rickard, Timothy C.; Bajic, Daniel

    2004-01-01

    A basic but unresolved issue in the study of memory retrieval is whether multiple independent cues can be used concurrently (i.e., in parallel) to recall a single, common response. A number of empirical results, as well as potentially applicable theories, suggest that retrieval can proceed in parallel, though Rickard (1997) set forth a model that…

  3. Working Memory in Children with Learning Disabilities in Reading versus Spelling: Searching for Overlapping and Specific Cognitive Factors

    ERIC Educational Resources Information Center

    Brandenburg, Janin; Klesczewski, Julia; Fischbach, Anne; Schuchardt, Kirsten; Büttner, Gerhard; Hasselhorn, Marcus

    2015-01-01

    In transparent orthographies like German, isolated learning disabilities in either reading or spelling are common and occur as often as a combined reading and spelling disability. However, most issues surrounding the cognitive causes of these isolated or combined literacy difficulties are yet unresolved. Recently, working memory dysfunctions have…

  4. Cooperative Learning: Homogeneous and Heterogeneous Grouping of Iranian EFL Learners in a Writing Context

    ERIC Educational Resources Information Center

    Zamani, Mona

    2016-01-01

    One of the important aspects of learning and teaching through cooperation is the group composition or grouping "who with whom". An unresolved issue is that of the superiority of heterogeneity or homogeneity in the structure of the groups. The present study was an attempt to investigate the impact that homogeneous and heterogeneous…

  5. Differential Labeling of Mental Illness by Social Status: A New Look at an Old Problem

    ERIC Educational Resources Information Center

    Thoits, Peggy A.

    2005-01-01

    Whether the higher rates of mental hospitalization and involuntary treatment for marginal social groups are due to differential labeling or simply to the occurrence of higher rates of disorder in these groups remains unresolved. I reexamine this issue with data from the National Comorbidity Survey (N = 5,877) that allow comparisons between…

  6. The U.S. draft guidance regarding population and individual bioequivalence approaches: comments by a research-based pharmaceutical company.

    PubMed

    Hauschke, D; Steinijans, V W

    2000-10-30

    Generally, the motivation for switching from average bioequivalence to population and/or individual bio-equivalence is well recognized in the light of certain limitations of the concept of average bioequivalence. However, this switch still results in unresolved issues which should be addressed before the regulatory guidance is finalized.

  7. Independent Confirmatory Factor Analysis of the Cognitive Assessment System (CAS): What Does CAS Measure?

    ERIC Educational Resources Information Center

    Kranzler, John H.; Keith, Timothy Z.

    1999-01-01

    Uses confirmatory factor analysis (CFA) to address unresolved issues concerning the structure of the Cognitive Assessment System, a test of intelligence based upon the planning, attention, and simultaneous-successive (PASS) processes theory of human cognition. Results reveal that the CFA of the standardization data do not support use of the CAS…

  8. Invention versus Direct Instruction: For Some Content, It's a Tie

    ERIC Educational Resources Information Center

    Chase, Catherine C.; Klahr, David

    2017-01-01

    An important, but as yet unresolved pedagogical question is whether discovery-oriented or direct instruction methods lead to greater learning and transfer. We address this issue in a study with 101 fourth and fifth grade students that contrasts two distinct instructional methods. One is a blend of discovery and direct instruction called…

  9. Revisiting the Energy Crisis: How Far Have We Come?

    ERIC Educational Resources Information Center

    Feldman, David Lewis

    1995-01-01

    This article is a summary of discussions that took place at a symposium attended by scholars and policymakers on the legacy of the 1970s energy crisis. Examines enduring impacts and unresolved issues, the possibility of a future embargo-style crisis, and the future of energy policy. Discusses energy and environment in developing countries. (LZ)

  10. The Marginalisation of Indigenous Students within School Mathematics and the Math Wars: Seeking Resolutions within Ethical Spaces

    ERIC Educational Resources Information Center

    Russell, Gale L.; Chernoff, Egan J.

    2013-01-01

    In mathematics education, there are (at least) two seemingly disparate and unethical issues that have been allowed to continue unresolved for decades: the math wars (traditional versus reform teaching and learning of mathematics) and the marginalisation of Indigenous students within K-12 mathematics. Willie Ermine, an Indigenous scholar, has…

  11. Does Imagined Practice Help in Learning a Motor Skill?

    ERIC Educational Resources Information Center

    Winters, Lynn; Reisberg, Daniel

    Several studies have shown an improvement in the performance of motor skills following imagined performance of the skill, or "mental practice." One unresolved issue has centered on whether the effect being observed is in fact a practice effect. As one alternative, the effect may be a simple instance of planning when to use a skill, or…

  12. Microbes are trophic analogues of arthropods, mammals, and fish: Isotopic fingerprinting unites ‘green’ and ‘brown’ food webs

    USDA-ARS?s Scientific Manuscript database

    This work addresses a cross-cutting issue within the field of food-web ecology—the integration of the microbiome into trophic hierarchies. The nature and degree to which microbes may reconfigure the trophic identities of carnivore and omnivore groups have remained surprisingly unresolved. This means...

  13. The Construct Validity of HPAT-Ireland for the Selection of Medical Students: Unresolved Issues and Future Research Implications

    ERIC Educational Resources Information Center

    Kelly, Maureen E.; O'Flynn, Siun

    2017-01-01

    Aptitude tests are widely used in selection. However, despite certain advantages their use remains controversial. This paper aims to critically appraise five sources of evidence for the construct validity of the Health Professions Admission Test (HPAT)-Ireland, an aptitude test used for selecting undergraduate medical students. The objectives are…

  14. Cost Issues Unresolved in Chicago

    ERIC Educational Resources Information Center

    Sawchuk, Stephen

    2012-01-01

    Chicago teachers voted last week to suspend a 7-day-old strike, sending some 350,000 students back to the classroom and paving the way for the teaching force to vote on a tentative contract. But for many in the Windy City, the contract has raised another potentially tall hurdle: how the cash-strapped district will manage to pay for it. District…

  15. Distractor Repetitions Retrieve Previous Responses and Previous Targets: Experimental Dissociations of Distractor-Response and Distractor-Target Bindings

    ERIC Educational Resources Information Center

    Giesen, Carina; Rothermund, Klaus

    2014-01-01

    Even an irrelevant distractor stimulus is integrated into event files. Subsequently repeating the distractor triggers retrieval of the event file; however, an unresolved issue concerns the question of "what" is retrieved by the distractor. While recent studies predominantly assume that the distractor retrieves the previous response, it…

  16. Health Professionals' Views of Communication: Implications for Assessing Performance on a Health-Specific English Language Test

    ERIC Educational Resources Information Center

    Elder, Cathie; Pill, John; Woodward-Kron, Robyn; McNamara, Tim; Manias, Elizabeth; Webb, Gillian; McColl, Geoff

    2012-01-01

    The gap between linguistic and professional criteria is a widely acknowledged but unresolved issue in the teaching and assessment of languages for specific purposes (LSP). In the teaching of professional writing, language experts and workplace professionals have been characterized as living worlds apart with respect to their views of…

  17. Family Interaction in the Newborn Period: Some Findings, Some Observations, and Some Unresolved Issues.

    ERIC Educational Resources Information Center

    Parke, Ross D.

    This paper presents two studies which explored the manner in which the father interacts with his newborn infant and compared paternal and maternal interaction patterns. In contrast to earlier studies, a direct observational approach was employed that permitted a detailed specification of father behaviors in the presence of the newborn. In the…

  18. Dynamic Modeling of Cell-Free Biochemical Networks Using Effective Kinetic Models

    DTIC Science & Technology

    2015-03-03

    whether we could simultaneously estimate kinetic parameters and regulatory connectivity, in the absence of specific mechanistic knowledge , from synthetic...that manage metabolism. Of course, these issues are not independent; any description of enzyme activity regulation will be a function of system state...the absence of specific mechanistic knowledge , from synthetic experimental data. Toward these questions, we explored five hypothetical cell-free

  19. Cardiometabolic risk in polycystic ovary syndrome.

    PubMed

    Bajuk Studen, Katica; Pfeifer, Marija

    2018-05-29

    Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk which is worsening with severity of androgen excess. Due to methodological difficulties longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.

  20. Dendritic excitation–inhibition balance shapes cerebellar output during motor behaviour

    PubMed Central

    Jelitai, Marta; Puggioni, Paolo; Ishikawa, Taro; Rinaldi, Arianna; Duguid, Ian

    2016-01-01

    Feedforward excitatory and inhibitory circuits regulate cerebellar output, but how these circuits interact to shape the somatodendritic excitability of Purkinje cells during motor behaviour remains unresolved. Here we perform dendritic and somatic patch-clamp recordings in vivo combined with optogenetic silencing of interneurons to investigate how dendritic excitation and inhibition generates bidirectional (that is, increased or decreased) Purkinje cell output during self-paced locomotion. We find that granule cells generate a sustained depolarization of Purkinje cell dendrites during movement, which is counterbalanced by variable levels of feedforward inhibition from local interneurons. Subtle differences in the dendritic excitation–inhibition balance generate robust, bidirectional changes in simple spike (SSp) output. Disrupting this balance by selectively silencing molecular layer interneurons results in unidirectional firing rate changes, increased SSp regularity and disrupted locomotor behaviour. Our findings provide a mechanistic understanding of how feedforward excitatory and inhibitory circuits shape Purkinje cell output during motor behaviour. PMID:27976716

  1. Neural plasticity of development and learning.

    PubMed

    Galván, Adriana

    2010-06-01

    Development and learning are powerful agents of change across the lifespan that induce robust structural and functional plasticity in neural systems. An unresolved question in developmental cognitive neuroscience is whether development and learning share the same neural mechanisms associated with experience-related neural plasticity. In this article, I outline the conceptual and practical challenges of this question, review insights gleaned from adult studies, and describe recent strides toward examining this topic across development using neuroimaging methods. I suggest that development and learning are not two completely separate constructs and instead, that they exist on a continuum. While progressive and regressive changes are central to both, the behavioral consequences associated with these changes are closely tied to the existing neural architecture of maturity of the system. Eventually, a deeper, more mechanistic understanding of neural plasticity will shed light on behavioral changes across development and, more broadly, about the underlying neural basis of cognition. (c) 2010 Wiley-Liss, Inc.

  2. Brief history of intermolecular and intersurface forces in complex fluid systems.

    PubMed

    Israelachvili, Jacob; Ruths, Marina

    2013-08-06

    We review the developments of ideas, concepts, and theories of intermolecular and intersurface forces and how these were influenced (or ignored) by observations of nature and, later, systematic experimentation. The emphasis of this review is on the way things gradually changed: experimentation replaced rhetoric, measurement and quantification replaced hand waving, energy replaced force in calculations, discrete atoms replaced the (continuum) aether, thermodynamics replaced mechanistic models, randomness and probability replaced certainty, and delicate experiments on the subnanoscale revealed fascinating self-assembling structures and complex behavior of even the simplest systems. We conclude by discussing today's unresolved challenges: how complex "dynamic" multicomponent--especially living biological--systems that receive a continuous supply of energy can be far from equilibrium and not even in any steady state. Such systems, never static but evolving in both space and time, are still far from being understood both experimentally and theoretically.

  3. The interplay between immunity and aging in Drosophila.

    PubMed

    Garschall, Kathrin; Flatt, Thomas

    2018-01-01

    Here, we provide a brief review of the mechanistic connections between immunity and aging-a fundamental biological relationship that remains poorly understood-by considering two intertwined questions: how does aging affect immunity, and how does immunity affect aging? On the one hand, aging contributes to the deterioration of immune function and predisposes the organism to infections ("immuno-senescence"). On the other hand, excessive activation of the immune system can accelerate degenerative processes, cause inflammation and immunopathology, and thus promote aging ("inflammaging"). Interestingly, several recent lines of evidence support the hypothesis that restrained or curbed immune activity at old age (that is, optimized age-dependent immune homeostasis) might actually improve realized immune function and thereby promote longevity. We focus mainly on insights from Drosophila , a powerful genetic model system in which both immunity and aging have been extensively studied, and conclude by outlining several unresolved questions in the field.

  4. Fluorescence Cross-Correlation Spectroscopy Reveals Mechanistic Insights into the Effect of 2′-O-Methyl Modified siRNAs in Living Cells

    PubMed Central

    Ohrt, Thomas; Staroske, Wolfgang; Mütze, Jörg; Crell, Karin; Landthaler, Markus; Schwille, Petra

    2011-01-01

    RNA interference (RNAi) offers a powerful tool to specifically direct the degradation of complementary RNAs, and thus has great therapeutic potential for targeting diseases. Despite the reported preferences of RNAi, there is still a need for new techniques that will allow for a detailed mechanistic characterization of RNA-induced silencing complex (RISC) assembly and activity to further improve the biocompatibility of modified siRNAs. In contrast to previous reports, we investigated the effects of 2′-O-methyl (2′OMe) modifications introduced at specific positions within the siRNA at the early and late stages of RISC assembly, as well as their influence on target recognition and cleavage directly in living cells. We found that six to 10 2′OMe nucleotides on the 3′-end inhibit passenger-strand release as well as target-RNA cleavage without changing the affinity, strand asymmetry, or target recognition. 2′OMe modifications introduced at the 5′-end reduced activated RISC stability, whereas incorporations at the cleavage site showed only minor effects on passenger-strand release when present on the passenger strand. Our new fluorescence cross-correlation spectroscopy assays resolve different steps and stages of RISC assembly and target recognition with heretofore unresolved detail in living cells, which is needed to develop therapeutic siRNAs with optimized in vivo properties. PMID:21689532

  5. Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity.

    PubMed

    Vantourout, Julien C; Miras, Haralampos N; Isidro-Llobet, Albert; Sproules, Stephen; Watson, Allan J B

    2017-04-05

    We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.

  6. Comparing Pleasure and Pain: The Fundamental Mathematical Equivalence of Reward Gain and Shock Reduction under Variable Interval Schedules

    ERIC Educational Resources Information Center

    Mallpress, Dave E. W.; Fawcett, Tim W.; McNamara, John M.; Houston, Alasdair I.

    2012-01-01

    The relationship between positive and negative reinforcement and the symmetry of Thorndike's law of effect are unresolved issues in operant psychology. Here we show that, for a given pattern of responding on variable interval (VI) schedules with the same programmed rate of food rewards (positive reinforcement VI) or electric shocks (negative…

  7. Equity for Cities in School Finance Reform: A Case for an "Equal Educational Offering" Standard in Public Education.

    ERIC Educational Resources Information Center

    Silard, John; And Others

    In this study, focus is upon the question of the standard for educational expenditure rather than on the alternative taxing methods for securing school district funding equalization. Chapter I begins by examining the major issues vital to urban education which the "Serrano" principle leaves unresolved. Then in Chapter II, particular elements of…

  8. Unresolved Issues and New Challenges in Teaching English to Young Learners: The Case of South Korea

    ERIC Educational Resources Information Center

    Garton, Sue

    2014-01-01

    The introduction of languages, especially English, into the primary curriculum around the world has been one of the major language-in-education policy developments in recent years. In countries where English has been compulsory for a number of years, the question arises as to what extent the numerous and well-documented challenges faced by the…

  9. Balancing Communities, Cultures, and Conflict: Lessons Learned From the East Ramapo School District Legal Battle

    ERIC Educational Resources Information Center

    Ober, Patrick; Decker, Janet R.

    2016-01-01

    This case illustrates why future school leaders must be prepared to handle complex legal and political issues that commonly arise in school districts today. We discuss a long-standing and unresolved legal battle between a Hasidic Jewish community and the public school district in East Ramapo, New York. In particular, we examine the difficulties…

  10. Magnetohydrodynamic turbulence in the solar wind

    NASA Technical Reports Server (NTRS)

    Matthaeus, W. H.; Goldstein, M. L.

    1983-01-01

    Recent work in describing the solar wind as an MHD turbulent fluid has shown that the magnetic fluctuations are adequately described as time stationary and to some extent as spatially homogeneous. Spectra of the three rugged invariants of incompressible MHD are the principal quantities used to characterize the velocity and magnetic field fluctuations. Unresolved issues concerning the existence of actively developing turbulence are discussed.

  11. The Oedipus Complex as Observed in Work with Couples and Their Children

    ERIC Educational Resources Information Center

    Miller, Lisa

    2004-01-01

    In work with couples where there is a child referred to a Child and Adolescent Mental Health Service, there are opportunities to observe and to work with unresolved Oedipal issues brought by the parents to the task of creating a family. These conflicts can be seen enacted by the child or children, either internally or externally. Examples are…

  12. Teaching Mathematical Problem-Solving with the Brain in Mind: How Can Opening a Closed Problem Help?

    ERIC Educational Resources Information Center

    Ambrus, András

    2014-01-01

    In the international literature, increasing numbers of articles and books are published about teaching and learning, with the brain in mind. For a long time, I have been sceptical about this question. However, seeing many unresolved issues in the teaching and learning of mathematics, I slowly started to study the relevant literature and have…

  13. Department of the Army Cost Analysis Manual

    DTIC Science & Technology

    2001-05-01

    SECTION I - AUTOMATED COST ESTIMATING INTEGRATED TOOLS ( ACEIT ) ................................................................179 SECTION II - AUTOMATED...Management & Comptroller) endorsed the Automated Cost Estimating Integrated Tools ( ACEIT ) model and since it is widely used to prepare POEs, CCAs and...CRB IPT (in ACEIT ) will be the basis for information contained in the CAB. Any remaining unresolved issues from the IPT process will be raised at the

  14. Canadian Policy--First Nation Involvement in the Funding and the Politics of Post-Secondary Education: How Much Is Enough?

    ERIC Educational Resources Information Center

    Lanceley, Darlene

    For Canada Natives, the unresolved issue of postsecondary education as a treaty right is at the center of discord in relation to budget constraints. The government's fiduciary responsibilities have devolved to First Nations administration, which allows for greater tribal control over the economics of individual First Nations and jurisdiction for…

  15. An Overview of School Dropout in Central America: Unresolved Issues and New Challenges for Education Progress

    ERIC Educational Resources Information Center

    Adelman, Melissa A.; Székely, Miguel

    2017-01-01

    School dropout is a growing concern in Central America, and in Latin America as a whole, because of its consequences for economic productivity, the inclusiveness of growth, social cohesion, and increasing youth risks. This paper utilizes more than two decades of household survey data to construct a systematic overview of school dropout at the…

  16. Eating disorders in adolescence: attachment issues from a developmental perspective

    PubMed Central

    Gander, Manuela; Sevecke, Kathrin; Buchheim, Anna

    2015-01-01

    In the present article we review findings from an emerging body of research on attachment issues in adolescents with eating disorders from a developmental perspective. Articles for inclusion in this review were identified from PsychINFO (1966–2013), Sciencedirect (1970–2013), Psychindex (1980–2013), and Pubmed (1980–2013). First, we will outline the crucial developmental changes in the attachment system and discuss how they might be related to the early onset of the disease. Then we will report on the major results from attachment studies using self-report and narrative instruments in that age group. Studies with a developmental approach on attachment will be analyzed in more detail. The high incidence of the unresolved attachment pattern in eating disorder samples is striking, especially for patients with anorexia nervosa. Interestingly, this predominance of the unresolved category was also found in their mothers. To date, these transgenerational aspects are still poorly understood and therefore represent an exciting research frontier. Future studies that include larger adolescent samples and provide a more detailed description including symptom severity and comorbidity would contribute to a better understanding of this complex and painful condition. PMID:26321974

  17. Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions.

    PubMed

    Arturi, F; Scarpelli, D; Coco, A; Sacco, R; Bruno, R; Filetti, S; Russo, D

    2003-04-01

    Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.

  18. The infant incubator in the neonatal intensive care unit: unresolved issues and future developments.

    PubMed

    Antonucci, Roberto; Porcella, Annalisa; Fanos, Vassilios

    2009-01-01

    Since the 19th century, devices termed incubators were developed to maintain thermal stability in low birth weight (LBW) and sick newborns, thus improving their chances of survival. Remarkable progress has been made in the production of infant incubators, which are currently highly technological devices. However, they still need to be improved in many aspects. Regarding the temperature and humidity control, future incubators should minimize heat loss from the neonate and eddies around him/her. An unresolved issue is exposure to high noise levels in the Neonatal Intensive Care Unit (NICU). Strategies aimed at modifying the behavior of NICU personnel, along with structural improvements in incubator design, are required to reduce noise exposure. Light environment should be taken into consideration in designing new models of incubators. In fact, ambient NICU illumination may cause visual pathway sequelae or possibly retinopathy of prematurity (ROP), while premature exposure to continuous lighting may adversely affect the rest-activity patterns of the newborn. Accordingly, both the use of incubator covers and circadian lighting in the NICU might attenuate these effects. The impact of electromagnetic fields (EMFs) on infant health is still unclear. However, future incubators should be designed to minimize the EMF exposure of the newborn.

  19. Vitamin D supplementation for osteoporosis in older adults: can we make it help better?

    PubMed

    Dong, C-H; Gao, Q-M; Wang, Z-M; Wang, A-M; Zhen, P

    2016-11-01

    With the increase of the average age of our population, the incidence of diseases specific for older adults has been increasing. One of such diseases is osteoporosis. The true incidence of osteoporosis is unknown. But the estimates indicate that this disease affects wide proportions of the population, ranging in millions or even ten millions in large countries like the United States. As this poses a significant burden on the health care system, interventions that could prevent or treat this condition are in the focus of clinical research. Vitamin D, the determinant of bone health, has been tested in clinical studies as the agent to treat osteoporosis. Despite the progress, there is still some controversy about the targeted blood levels of vitamin D, most efficient way to supplement this vitamin, and clinical efficacy of this supplementation in the elderly.In the present review, we will highlight the metabolism of vitamin D and the aforementioned unresolved issues, as well as review the recent interventional studies on vitamin D supplementation. In the present review, we will highlight the metabolism of vitamin D and the aforementioned unresolved issues, as well as review the recent interventional studies on vitamin D supplementation.

  20. Retroviruses Hijack Chromatin Loops to Drive Oncogene Expression and Highlight the Chromatin Architecture around Proto-Oncogenic Loci

    PubMed Central

    Pattison, Jillian M.; Wright, Jason B.; Cole, Michael D.

    2015-01-01

    The majority of the genome consists of intergenic and non-coding DNA sequences shown to play a major role in different gene regulatory networks. However, the specific potency of these distal elements as well as how these regions exert function across large genomic distances remains unclear. To address these unresolved issues, we closely examined the chromatin architecture around proto-oncogenic loci in the mouse and human genomes to demonstrate a functional role for chromatin looping in distal gene regulation. Using cell culture models, we show that tumorigenic retroviral integration sites within the mouse genome occur near existing large chromatin loops and that this chromatin architecture is maintained within the human genome as well. Significantly, as mutagenesis screens are not feasible in humans, we demonstrate a way to leverage existing screens in mice to identify disease relevant human enhancers and expose novel disease mechanisms. For instance, we characterize the epigenetic landscape upstream of the human Cyclin D1 locus to find multiple distal interactions that contribute to the complex cis-regulation of this cell cycle gene. Furthermore, we characterize a novel distal interaction upstream of the Cyclin D1 gene which provides mechanistic evidence for the abundant overexpression of Cyclin D1 occurring in multiple myeloma cells harboring a pathogenic translocation event. Through use of mapped retroviral integrations and translocation breakpoints, our studies highlight the importance of chromatin looping in oncogene expression, elucidate the epigenetic mechanisms crucial for distal cis-regulation, and in one particular instance, explain how a translocation event drives tumorigenesis through upregulation of a proto-oncogene. PMID:25799187

  1. Space station human productivity study. Volume 5: Management plans

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The 67 Management Plans represent recommended study approaches for resolving 108 of the 305 Issues which were identified. Each study Management Plan is prepared in three formats: Management Plan Overview (lists the subsumed Issues, study background, and related overview information); Study Plan (details the study approach by tasks, lists special needs, and describes expected study products); Schedule-Task Flow (provides a time-lined schedule for the study tasks and resource requirements). The Management Relationships Matrix, included in this volume, shows the data input-output relationships among all recommended studies. A listing is also included which cross-references the unresolved requirements to Issues to management plans. A glossary of all abbreviations utilized is provided.

  2. Prospective Assessment of Neurocognition in Future Gulf-deployed and Gulf-nondeployed Military Personnel: A Pilot Study

    DTIC Science & Technology

    2007-02-01

    increased emotional distress but with advantaged simple reactiontime. Unit cohesion buffers the adverse effects of early life events on PTSD prior to...motor speed), and emotional (e.g., mood) behaviors thought to reflect neural integrity. Unresolved issues include whether subjective...including neurobehavioral and emotional functioning, (b) examine the impact of deployment-related stress and environmental exposures on

  3. Implicit Learning in the Crowd: Investigating the Role of Awareness in the Acquisition of L2 Knowledge

    ERIC Educational Resources Information Center

    Kerz, Elma; Wiechmann, Daniel; Riedel, Florian B.

    2017-01-01

    A growing field of research has made use of a semiartificial language paradigm to investigate the role of awareness in L2 acquisition. A central and empirically still unresolved issue in this field concerns the possibility of learning implicitly, that is, without intention to learn and without awareness of what has been learned. Up until now,…

  4. Exercise Ventilatory Limitation: The Role Of Expiratory Flow Limitation

    PubMed Central

    Babb, Tony G.

    2012-01-01

    Ventilatory limitation to exercise remains an important unresolved clinical issue; as a result, many individuals misinterpret the effects of expiratory flow limitation as an all-or-nothing phenomenon. Expiratory flow limitation is not all-or-none; approaching maximal expiratory flow can have important effects not only on ventilatory capacity but also on breathing mechanics, ventilatory control, and possibly exertional dyspnea and exercise intolerance. PMID:23038244

  5. The Effectiveness of Instructor Personalized and Formative Feedback Provided by Instructor in an Online Setting: Some Unresolved Issues

    ERIC Educational Resources Information Center

    Planar, Dolors; Moya, Soledad

    2016-01-01

    Formative feedback has great potential for teaching and learning in online undergraduate programmes. There is a large number of courses where the main source of feedback is provided by the instructor. This is particularly seen in subjects where assessments are designed based on specific activities which are the same for all students, and where the…

  6. Diabetic Cardiomyopathy: Bench to Bedside

    PubMed Central

    Schilling, Joel D.; Mann, Douglas L.

    2012-01-01

    The study of diabetic cardiomyopathy (diabetic CM) is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic CM with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. PMID:22999244

  7. Mean Length of Utterance in Children with Specific Language Impairment and in Younger Control Children Shows Concurrent Validity and Stable and Parallel Growth Trajectories

    ERIC Educational Resources Information Center

    Rice, Mabel L.; Redmond, Sean M.; Hoffman, Lesa

    2006-01-01

    Purpose: Although mean length of utterance (MLU) is a useful benchmark in studies of children with specific language impairment (SLI), some empirical and interpretive issues are unresolved. The authors report on 2 studies examining, respectively, the concurrent validity and temporal stability of MLU equivalency between children with SLI and…

  8. Teacher Collaboration Praxis: Conflicts, Borders, and Ideologies from a Micropolitical Perspective (La práctica colaborativa entre docentes: conflictos, fronteras e ideologías desde una perspectiva micropolítica)

    ERIC Educational Resources Information Center

    Keranen, Nancy; Encinas Prudencio, Fátima

    2014-01-01

    This paper looks at a feature of teacher collaboration within Achinstein's (2002) micropolitics of collaboration but from an intrapersonal perspective. Results discussed feature issues of conflict, borders, and ideologies within each participating teacher rather than between teachers. Unresolved or unacknowledged intrapersonal conflict might lead…

  9. Character Building or Subversive Consequences of Employment during High School: Causal Effects Based on Propensity Score Models for Categorical Treatments

    ERIC Educational Resources Information Center

    Nagengast, Benjamin; Marsh, Herbert W.; Chiorri, Carlo; Hau, Kit-Tai

    2014-01-01

    The present study revisited the unresolved issue of the long-term effects of part-time working intensity during high school on students' achievement, participation in postsecondary education, time allocation, and work-related values and expectations. Using data from the Educational Longitudinal Study of 2002 (N = 14,654), the effects of part-time…

  10. Heart Failure: From Research to Clinical Practice.

    PubMed

    Islam, Md Shahidul

    2018-01-01

    "Heart failure: from research to clinical practice", a collection of selected reviews, which comes out also as a book, covers essentially all important aspects of heart failure, including the pathogenesis, clinical features, biomarkers, imaging techniques, medical treatment and surgical treatments, use of pacemakers and implantable cardioverter defibrillators, and palliative care. The reviews include essential background information, state of the art, critical and in-depth analysis, and directions for future researches for elucidation of the unresolved issues. Everyone interested in heart failure is expected to find this compilation helpful for a deeper understanding of some of the complex issues.

  11. Characterization and management of electrical noise in the new Australian military HF communication network

    NASA Astrophysics Data System (ADS)

    Vyden, Bruce

    2000-03-01

    The Australian Defense Force's (ADF's) High Frequency (HF) communication network is soon to be replaced by a modernized system. Characterization of electrical noise at the receiver sites proposed for the new system is crucial to its performance. Consequently receiver site noise will be measured under the HF Modernization implementation contract that was awarded to Boeing Australia Ltd. Unfortunately the utility of the noise measurements is constrained by the uncertainties of both the ionosphere and atmosphere. This paper discusses some of the issues related to the methodology for measuring the noise and exposes some unresolved issues.

  12. Pilot workload and fatigue: A critical survey of concepts and assessment techniques

    NASA Technical Reports Server (NTRS)

    Gartner, W. B.; Murphy, M. R.

    1976-01-01

    The principal unresolved issues in conceptualizing and measuring pilot workload and fatigue are discussed. These issues are seen as limiting the development of more useful working concepts and techniques and their application to systems engineering and management activities. A conceptual analysis of pilot workload and fatigue, an overview and critique of approaches to the assessment of these phenomena, and a discussion of current trends in the management of unwanted workload and fatigue effects are presented. Refinements and innovations in assessment methods are recommended for enhancing the practical significance of workload and fatigue studies.

  13. Fundamental issues in the geology and geophysics of venus.

    PubMed

    Solomon, S C; Head, J W

    1991-04-12

    A number of important and currently unresolved issues in the global geology and geophysics of Venus will be addressable with the radar imaging, altimetry, and gravity measurements now forthcoming from the Magellan mission. Among these are the global volcanic flux and the rate of formation of new crust; the global heat flux and its regional variations; the relative importance of localized hot spots and linear centers of crustal spreading to crustal formation and tectonics; and the planform of mantle convection on Venus and the nature of the interactions among interior convective flow, near-surface deformation and magmatism.

  14. Identifying ethical issues of the Department of the Army civilian and Army Nurse Corps certified registered nurse anesthetists.

    PubMed

    Jenkins, Constance L; Elliott, Aaron R; Harris, Janet R

    2006-08-01

    The purposes of this study were to identify the ethical issues Department of the Army civilian and Army Nurse Corps certified registered nurse anesthetists (CRNAs) encountered in their anesthesia practice and how disturbed they were by these issues. This descriptive study used a secondary data analysis of a cross-sectional survey of Army Nurse Corps officers and Department of the Army civilian registered nurses (N = 5,293). The CRNA subset (n = 97) was obtained from questionnaires that indicated a primary practice setting as anesthesia. The most frequently occurring ethical issue identified was conflict in the nurse-physician relationship, whereas the most disturbing issue was working with incompetent/impaired colleagues. Unresolved ethical conflicts can negatively influence the nurses' morale, leading to avoidance of the issue and contributing to burnout. Identifying the ethical issues and disturbance level experienced by CRNAs should contribute to the development of an ethics education program that addresses issues encountered in CRNA practice.

  15. Capital Structure and Stock Returns

    ERIC Educational Resources Information Center

    Welch, Ivo

    2004-01-01

    U.S. corporations do not issue and repurchase debt and equity to counteract the mechanistic effects of stock returns on their debt-equity ratios. Thus over one- to five-year horizons, stock returns can explain about 40 percent of debt ratio dynamics. Although corporate net issuing activity is lively and although it can explain 60 percent of debt…

  16. Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2014-01-01

    Unresolved mourning is marked by disorganized behavior and states of mind. In this study, we speculated that pathological dissociation would mediate the effects of unresolved mourning on supernatural beliefs. This hypothesis was determined based on findings that indicate an association between higher levels of dissociation, stronger beliefs in the supernatural and unresolved mourning. We examined two groups of participants, one classified as non-unresolved (non-U) (n = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma as measured by the Adult Attachment Interview (AAI). Two self-report instruments were administered to measure supernatural beliefs and dissociation. As hypothesized, the multivariate analysis of variance indicated mean differences between the two groups. The unresolved group had greater belief in the supernatural and more pathological dissociative processes. The mediation analysis demonstrated that pathological dissociation fully mediated the effects of unresolved mourning on supernatural beliefs.

  17. Integrative dimensions of psychotherapy training.

    PubMed

    Greben, Daniel H

    2004-04-01

    This paper investigates the influence of integrative factors on psychotherapy education. The broad relevance of integrative psychotherapy to residency training and continuing mental health education is discussed. Following a review of the existing literature on the education of integrative psychotherapists, the article systematically examines the integrative and pedagogic issues to be considered in planning psychotherapy training informed by integrative principles. The integrative issues are organized into 5 categories: attitudinal set, knowledge base, clinical techniques and skills, developmental tasks and challenges, and systemic institutional factors. The educational issues can be divided into 4 categories: content, format and process, sequence, and faculty development. Brief descriptions of actual educational interventions illustrate the implementation of such ideas. Specific recommendations are made regarding the development of integrative educational initiatives and future study of unresolved questions.

  18. Bigeye Bomb: Unresolved Development Issues

    DTIC Science & Technology

    1989-08-11

    the lethal agent formed inside the Bigeye bomb) at the purity or equivalent- biotoxicity level required by the Test and Eval- uation Master Plan (TEMP...during the 5 through 30-second period after mixing starts, with- out specifying either wheit the required purity or equivalent biotoxicity level should...revision of the purity or equivalent biotoxicity requirement. However, we believe that a bomb that produces lethal agent at the required purity level for 1

  19. Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide.

    PubMed

    Cano, Antonio; Chedraui, Peter; Goulis, Dimitrios G; Lopes, Patrice; Mishra, Gita; Mueck, Alfred; Senturk, Levent M; Simoncini, Tommaso; Stevenson, John C; Stute, Petra; Tuomikoski, Pauliina; Rees, Margaret; Lambrinoudaki, Irene

    2018-01-01

    Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. Literature review and consensus of expert opinion. The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Mechanistic kinetic models of enzymatic cellulose hydrolysis-A review.

    PubMed

    Jeoh, Tina; Cardona, Maria J; Karuna, Nardrapee; Mudinoor, Akshata R; Nill, Jennifer

    2017-07-01

    Bioconversion of lignocellulose forms the basis for renewable, advanced biofuels, and bioproducts. Mechanisms of hydrolysis of cellulose by cellulases have been actively studied for nearly 70 years with significant gains in understanding of the cellulolytic enzymes. Yet, a full mechanistic understanding of the hydrolysis reaction has been elusive. We present a review to highlight new insights gained since the most recent comprehensive review of cellulose hydrolysis kinetic models by Bansal et al. (2009) Biotechnol Adv 27:833-848. Recent models have taken a two-pronged approach to tackle the challenge of modeling the complex heterogeneous reaction-an enzyme-centric modeling approach centered on the molecularity of the cellulase-cellulose interactions to examine rate limiting elementary steps and a substrate-centric modeling approach aimed at capturing the limiting property of the insoluble cellulose substrate. Collectively, modeling results suggest that at the molecular-scale, how rapidly cellulases can bind productively (complexation) and release from cellulose (decomplexation) is limiting, while the overall hydrolysis rate is largely insensitive to the catalytic rate constant. The surface area of the insoluble substrate and the degrees of polymerization of the cellulose molecules in the reaction both limit initial hydrolysis rates only. Neither enzyme-centric models nor substrate-centric models can consistently capture hydrolysis time course at extended reaction times. Thus, questions of the true reaction limiting factors at extended reaction times and the role of complexation and decomplexation in rate limitation remain unresolved. Biotechnol. Bioeng. 2017;114: 1369-1385. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Pooled Patient-Level Meta-analysis of Children and Adults Completing a Computer-Based Anxiety Intervention Targeting Attentional Bias

    PubMed Central

    Price, Rebecca B.; Wallace, Meredith; Kuckertz, Jennie M.; Amir, Nader; Graur, Simona; Cummings, Logan; Popa, Paul; Carlbring, Per; Bar-Haim, Yair

    2016-01-01

    Computer-based approaches, such as Attention Bias Modification (ABM), could help improve access to care for anxiety. Study-level meta-analyses of ABM have produced conflicting findings and leave critical questions unresolved regarding ABM’s mechanisms of action and clinical potential. We pooled patient-level datasets from randomized controlled trials of children and adults with high-anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was tested as an outcome and a mechanistic mediator and moderator of anxiety reduction. Diagnostic remission and Liebowitz Social Anxiety Scale (LSAS) were clinical outcomes available in enough studies to enable pooling. Per-patient data were obtained on at least one outcome from 13/16 eligible studies [86% of eligible participants; n=778]. Significant main effects of ABM on diagnostic remission (ABM—22.6%, control—10.8%; OR=2.57; p=.006) and AB (β*(95%CI)=−.63(−.83, −.42); p<.00005) were observed. There was no main effect of ABM on LSAS. However, moderator analyses suggested ABM was effective for patients who were younger (≤37y), trained in the lab, and/or assessed by clinicians. Under the same conditions where ABM was effective, mechanistic links between AB and anxiety reduction were supported. Under these specific circumstances, ABM reduces anxiety and acts through its target mechanism, supporting ABM’s theoretical basis while simultaneously suggesting clinical indications and refinements to improve its currently limited clinical potential. PMID:27693664

  2. Show me the money: the implications of Schedule H.

    PubMed

    Salinsky, Eileen

    2009-04-21

    Responding to policymakers' concerns, the Internal Revenue Service (IRS) implemented significant new hospital community benefit reporting under Schedule H of its revised Form 990, the return used by tax-exempt organizations. This issue brief considers the policy implications of the quantitative and qualitative information that hospitals are now mandated to report through Schedule H, including the costs associated with charity care, bad debt, and the unreimbursed costs of Medicaid and Medicare. The paper examines unresolved issues related to the new reporting requirements, such as controversies regarding the scope of Schedule H, and considers the potential for these reports to influence IRS oversight activities, legislative action, and hospital policies and practices.

  3. High-rise housing in the city of Samara: the first steps on the path to sustainable development

    NASA Astrophysics Data System (ADS)

    Vavilova, Tatiana Ya.; Makeeva, Elena Yu.

    2018-03-01

    This paper outlines theoretical background of high-rise housing and discusses its design experience. It particularly focuses on environmental, social and economic aspects which are among crucial sustainable development issues. The authors dwell upon the implementation of innovative solutions that meet principles and goals of sustainable development and take construction objects built in Samara (which is one of the largest metropolises in Russia) as an example. The research also investigates the quality of project designs and reveals techniques corresponding to the "green standards". It considers the issues of practicing high-rise building construction in specific urban conditions and identifies unresolved architectural problems.

  4. Auditory subliminal stimulation: a re-examination.

    PubMed

    Urban, M J

    1992-04-01

    Unconscious or subliminal perception has historically been a thorny issue in psychology. It has been the subject of debate and experimentation since the turn of the century. While psychologists now agree that the phenomenon of visual subliminal stimulation is real, disagreement continues over the effects of such stimulation as well as to its existence in other sensory modalities, notably the auditory. The present paper provides an overview of unresolved issues in auditory subliminal stimulation which explains much of the difficulty that has been encountered in experimental work in this area. A context is proposed for considering the effects of auditory subliminal stimulation and an overview of current investigations in this field is provided.

  5. Cancer genetics meets biomolecular mechanism-bridging an age-old gulf.

    PubMed

    González-Sánchez, Juan Carlos; Raimondi, Francesco; Russell, Robert B

    2018-02-01

    Increasingly available genomic sequencing data are exploited to identify genes and variants contributing to diseases, particularly cancer. Traditionally, methods to find such variants have relied heavily on allele frequency and/or familial history, often neglecting to consider any mechanistic understanding of their functional consequences. Thus, while the set of known cancer-related genes has increased, for many, their mechanistic role in the disease is not completely understood. This issue highlights a wide gap between the disciplines of genetics, which largely aims to correlate genetic events with phenotype, and molecular biology, which ultimately aims at a mechanistic understanding of biological processes. Fortunately, new methods and several systematic studies have proved illuminating for many disease genes and variants by integrating sequencing with mechanistic data, including biomolecular structures and interactions. These have provided new interpretations for known mutations and suggested new disease-relevant variants and genes. Here, we review these approaches and discuss particular examples where these have had a profound impact on the understanding of human cancers. © 2018 Federation of European Biochemical Societies.

  6. On Retirement of Physicians

    PubMed Central

    Levy, Roy

    1986-01-01

    This article takes a look at retirement in general, and the implications for physicians in particular. The recent application of the principles in the Canadian Charter of Rights has raised some unresolved issues for those doctors with contractual employment. They may no longer have mandatory retirement at age 65. Problems can and do arise when self-employed physicians defer retirement from active practice indefinitely. The evaluation of older physicians' competence is explored, and some suggestions offered. PMID:21267269

  7. Tendinopathy: Investigating the Intersection of Clinical and Animal Research to Identify Progress and Hurdles in the Field

    PubMed Central

    Titan, Ashley; Andarawis-Puri, Nelly

    2017-01-01

    Biological treatments, surgical interventions, and rehabilitation exercises have been successfully used to treat tendinopathy, but the development of effective treatments has been hindered by the lack of mechanistic data regarding the pathogenesis of the disease.While insightful, clinical studies are limited in their capacity to provide data regarding the pathogenesis of tendinopathies, emphasizing the value of animal models and cell culture studies to fill this essential gap in knowledge.Clinical pathological findings from imaging studies or histological analysis are not universal across patients with tendinopathy and have not been clearly associated with the onset of symptoms.There are several unresolved controversies, including the cellular changes that accompany the tendinopathic disease state and the role of inflammation.Additional research is needed to correlate the manifestations of the disease with its pathogenesis, with the goal of reaching a field-wide consensus on the pathology of the disease state. Such a consensus will allow standardized clinical practices to more effectively diagnose and treat tendinopathy. PMID:27792676

  8. TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.

    PubMed

    Graham, Daniel B; Lefkovith, Ariel; Deelen, Patrick; de Klein, Niek; Varma, Mukund; Boroughs, Angela; Desch, A Nicole; Ng, Aylwin C Y; Guzman, Gaelen; Schenone, Monica; Petersen, Christine P; Bhan, Atul K; Rivas, Manuel A; Daly, Mark J; Carr, Steven A; Wijmenga, Cisca; Xavier, Ramnik J

    2016-12-13

    Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5-61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking.

    PubMed

    Sato, A; Nishida, C; Sato-Kusubata, K; Ishihara, M; Tashiro, Y; Gritli, I; Shimazu, H; Munakata, S; Yagita, H; Okumura, K; Tsuda, Y; Okada, Y; Tojo, A; Nakauchi, H; Takahashi, S; Heissig, B; Hattori, K

    2015-01-01

    The systemic inflammatory response observed during acute graft-versus-host disease (aGVHD) is driven by proinflammatory cytokines, a 'cytokine storm'. The function of plasmin in regulating the inflammatory response is not fully understood, and its role in the development of aGVHD remains unresolved. Here we show that plasmin is activated during the early phase of aGVHD in mice, and its activation correlated with aGVHD severity in humans. Pharmacological plasmin inhibition protected against aGVHD-associated lethality in mice. Mechanistically, plasmin inhibition impaired the infiltration of inflammatory cells, the release of membrane-associated proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and Fas-ligand directly, or indirectly via matrix metalloproteinases (MMPs) and alters monocyte chemoattractant protein-1 (MCP-1) signaling. We propose that plasmin and potentially MMP-9 inhibition offers a novel therapeutic strategy to control the deadly cytokine storm in patients with aGVHD, thereby preventing tissue destruction.

  10. Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis

    PubMed Central

    Luitz, Manuel P.; Bomblies, Rainer; Ramcke, Evelyn; Itzen, Aymelt; Zacharias, Martin

    2016-01-01

    The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins. PMID:26818796

  11. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

    PubMed

    Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

    2016-08-18

    Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Tightly Coupled Mechanistic Study of Materials in the Extreme Space Environment

    DTIC Science & Technology

    2016-10-11

    to examine spacecraft contamination issues from the perspective of non- equilibrium gas dynamics (Levin), material response at the atomistic level...Space Environment Group has worked to examine spacecraft contamination issues from the perspective of non- equilibrium gas dynamics (Levin...material response at the atomistic level (Rajan), high fidelity gas -surface chemistry models (van Duin), and experiments to characterize and test

  13. A review on the current issues and barriers of Industrialised Building System (IBS) adoption in Malaysia’s construction industry

    NASA Astrophysics Data System (ADS)

    Amin, M. A. Mohd; Abas, N. H.; Shahidan, S.; Rahmat, M. H.; Suhaini, N. A.; Nagapan, S.; Rahim, R. Abdul

    2017-11-01

    Malaysia considers the construction industry as one of the main contributors to its Gross Domestic Product (GDP). However, there are some unresolved issues arising from the ongoing and widespread adoption of the conventional method of construction such as the resultant fragmentation of the industry itself; delays in production and delivery time of unnecessary wastages and lack of sustainability practice. Malaysian Government has been continuously encouraging the industry to use, partly or if not wholly, the Industrialized Building System (IBS), which is considered to be an important part of sustainable construction initiative. IBS was introduced to Malaysia as the solution to issues related to dependencies of foreign workers, raising demand for affordable accommodations and improving image, quality and productivity of construction industry. However, the IBS adoption in Malaysia remains low. This paper presents the review of the current issues and barriers of IBS adoption in Malaysian construction industry.

  14. External Validity in the Study of Human Development: Theoretical and Methodological Issues

    ERIC Educational Resources Information Center

    Hultsch, David F.; Hickey, Tom

    1978-01-01

    An examination of the concept of external validity from two theoretical perspectives: a traditional mechanistic approach and a dialectical organismic approach. Examines the theoretical and methodological implications of these perspectives. (BD)

  15. Status of NO sub x control for coal-fired power plants

    NASA Technical Reports Server (NTRS)

    Teixeira, D. P.

    1978-01-01

    The status of technologies for controlling emissions of oxides of nitrogen (NOx) from coal-fired power plants is reviewed. A discussion of current technology as well as future NOx control approaches is presented. Advanced combustion approaches are included as well as post-combustion alternatives such as catalytic and noncatalytic ammonia-bases systems and wet scrubbing. Special emphasis is given to unresolved development issues as they relate to practical applications on coal-fired power plants.

  16. MCNP/X TRANSPORT IN THE TABULAR REGIME

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    HUGHES, H. GRADY

    2007-01-08

    The authors review the transport capabilities of the MCNP and MCNPX Monte Carlo codes in the energy regimes in which tabular transport data are available. Giving special attention to neutron tables, they emphasize the measures taken to improve the treatment of a variety of difficult aspects of the transport problem, including unresolved resonances, thermal issues, and the availability of suitable cross sections sets. They also briefly touch on the current situation in regard to photon, electron, and proton transport tables.

  17. Shock and Awe. Achieving Rapid Dominance

    DTIC Science & Technology

    1996-09-01

    par- adox of the issue of planning for a long - versus -short war in a nuclear world remained unresolved. 4 Shock and AweMobilization, as in World War...world and are likely to remain so for a long time to come. Why then, many will ask, should we examine and even propose major excursions and...after battle. Today, x we believe that an unusual opportunity exists to determine whether or not this long -sought strategic goal of affecting the

  18. Understanding Cultural Landmines in the Balkans: How the Land and Its History Have Kept a People at War

    DTIC Science & Technology

    2001-10-01

    property , forcible eviction of entire villages, widespread rape and torture, and massacres of innocent women, children, and the elderly BALKANS-1 6...and Italy also have unresolved issues dating from World War II over property and ethnic minority rights. Serbia and Montenegro also dispute Croatia’s...positions (Jayne, 1910). Dating from the Ottoman occupation, Moslem nobles and landlords held all land other than gardens and residential properties

  19. The P-38 Lightning Aircraft: Lessons Learned for Future Weapon Systems Development

    DTIC Science & Technology

    2010-04-01

    PMBOK TEL \\ u.s. WER List of ~cronyms iv Brake Horse Power Design-Build Team District of Columbia Department of Defense Department of...record. Despite unresolved issues like the flap and brake system problems and limited test hours, on 11 February 1939, Lieutenant Kelsey flew the XP-38...engine, giving the P-3 8 engines a 1425 brake horse power (BHP)22 rating. However, limitations of the integral wing leading edge intercoolers23 could

  20. Interactions Between Structure and Processing that Control Moisture Uptake in High-Performance Polycyanurates (Briefing Charts)

    DTIC Science & Technology

    2015-03-24

    distribution is unlimited.  . Interactions Between Structure and Processing that Control Moisture Uptake in High-Performance Polycyanurates Presenter: Dr...Edwards AFB, CA 4 California State University, Long Beach, CA 90840 2 Outline: Basic Studies of Moisture Uptake in Cyanate Ester Networks • Background...Motivation • SOTA Theories of Moisture Uptake in Thermosetting Networks • New Tools and New Discoveries • Unresolved Issues and Ways to Address Them

  1. A rederivation of the conformal anomaly for spin-{\\frac{1}{2}}

    NASA Astrophysics Data System (ADS)

    Godazgar, Hadi; Nicolai, Hermann

    2018-05-01

    We rederive the conformal anomaly for spin- fermions by a genuine Feynman graph calculation, which has not been available so far. Although our calculation merely confirms a result that has been known for a long time, the derivation is new, and thus furnishes a method to investigate more complicated cases (in particular concerning the significance of the quantum trace of the stress tensor in non-conformal theories) where there remain several outstanding and unresolved issues.

  2. Implementing advanced nurse practitioner roles in acute care: an evaluation of organizational change.

    PubMed

    Cummings, Greta G; Fraser, Kim; Tarlier, Denise S

    2003-03-01

    Medical shortages are seen as the driving force behind the recent implementation of the advanced nurse practitioner (ANP) role in some Canadian hospitals. The authors analyzed the implementation of the ANP role in one tertiary care teaching hospital from the organizational change perspective. Despite successful implementation, issues of role definition, scope of practice boundaries, and staff reactions remain unresolved. Recommendations are discussed for implementing ANP roles in other acute care facilities.

  3. A biologic perspective on sexual orientation.

    PubMed

    Pillard, R C; Bailey, J M

    1995-03-01

    Sexual orientation may be defined as the sustained erotic attraction to members of one's own gender, the opposite gender, or both--homosexual, heterosexual, or bisexual, respectively. Interest in sexual orientation is as old as the science of psychology, yet many fundamental issues remain unresolved. This article reviews research in the development and psychopathology of sexual orientation as well as the results of family and twin studies. Research in genetic linkage, sex hormones, and brain differences also is discussed.

  4. The Image of the 1967 War in Israeli History Textbooks as Test Case: Studying an Active Past in a Protracted Regional Conflict

    ERIC Educational Resources Information Center

    Yogev, Esther

    2012-01-01

    This article seeks to shed light on the dilemma facing history education in regions beset by a protracted, and as yet unresolved ethno-political conflict. The article will examine this issue by means of a unique test case that observes a dramatic war event in Israeli textbooks. The event in question is the Six-Day War of 1967 and the study of its…

  5. How Do Individuals Develop Alcohol Use Disorder After Bariatric Surgery? A Grounded Theory Exploration.

    PubMed

    Yoder, Ruth; MacNeela, Padraig; Conway, Ronan; Heary, Caroline

    2018-03-01

    Bariatric surgery is the most effective treatment for severe obesity. However, following Roux-en-Y gastric bypass (RYGB) surgery, a small minority of patients develop new-onset alcohol use disorder (AUD), the aetiology of which is poorly understood. The aim is to construct a theory to explain the development of AUD among a sample of individuals who reported problematic drinking following RYGB. Semi-structured interviews were conducted with eight RYGB patients diagnosed with AUD attending a multi-disciplinary outpatient weight management service at a public hospital in the Republic of Ireland. A constructivist grounded theory methodology was used to analyse interview transcripts. Participants' main concern was identified as 'unresolved psychological issues' which were managed by 'external coping mechanisms', namely, 'eating to cope'. After RYGB, comfort eating was no longer possible to the same extent. Following a 'honeymoon period', participants' need for an external coping mechanism resurfaced. 'Filling the void' provides a framework to explain how participants managed the symptoms of their unresolved psychological issues through 'behavioural substitution', that is, drinking alcohol instead of eating. The theoretical framework of 'filling the void' adds to contemporary research that conceptualises AUD behavioural substitution as 'addiction transfer' by describing the process by which the phenomenon occurs as well as the characteristics of participants. The clinical implication of this research is to advocate for a reshaping of treatment of RYGB patients, with increased psychological input following surgery.

  6. The ethics of human volunteer studies involving experimental exposure to pesticides: unanswered dilemmas

    PubMed Central

    2010-01-01

    The controversy about the use of data from human volunteer studies involving experimental exposure to pesticides as part of regulatory risk assessment has been widely discussed, but the complex and interrelated scientific and ethical issues remain largely unresolved. This discussion paper, generated by authors who comprised a workgroup of the ICOH Scientific Committee on Rural Health, reviews the use of human experimental studies in regulatory risk assessment for pesticides with a view to advancing the debate as to when, if ever, such studies might be ethically justifiable. The discussion is based on three elements: (a) a review of discussion papers on the topic of human testing of pesticides and the positions adopted by regulatory agencies in developed countries; (b) an analysis of published and unpublished studies involving human testing with pesticides, both in the peer-reviewed literature and in the JMPR database; and (c) application of an ethical analysis to the problem. The paper identifies areas of agreement which include general principles that may provide a starting point on which to base criteria for judgements as to the ethical acceptability of such studies. However, the paper also highlights ongoing unresolved differences of opinion inherent in ethical analysis of contentious issues, which we propose should form a starting point for further debate and the development of guidelines to achieve better resolution of this matter. PMID:20718963

  7. Combining the ‘bottom up’ and ‘top down’ approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data

    PubMed Central

    Tsamandouras, Nikolaos; Rostami-Hodjegan, Amin; Aarons, Leon

    2015-01-01

    Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate outside the studied population and experimental conditions. The trade-off for this advantage is a complex system of differential equations with a considerable number of model parameters. When these parameters cannot be informed from in vitro or in silico experiments they are usually optimized with respect to observed clinical data. Parameter estimation in complex models is a challenging task associated with many methodological issues which are discussed here with specific recommendations. Concepts such as structural and practical identifiability are described with regards to PBPK modelling and the value of experimental design and sensitivity analyses is sketched out. Parameter estimation approaches are discussed, while we also highlight the importance of not neglecting the covariance structure between model parameters and the uncertainty and population variability that is associated with them. Finally the possibility of using model order reduction techniques and minimal semi-mechanistic models that retain the physiological-mechanistic nature only in the parts of the model which are relevant to the desired modelling purpose is emphasized. Careful attention to all the above issues allows us to integrate successfully information from in vitro or in silico experiments together with information deriving from observed clinical data and develop mechanistically sound models with clinical relevance. PMID:24033787

  8. Attachment theory: progress and future directions.

    PubMed

    Fearon, R M Pasco; Roisman, Glenn I

    2017-06-01

    Attachment is a key subfield in the area of parenting and parent-child relationships research. In this brief overview, we summarise what we consider to be the state-of-the-art of attachment research, focusing primarily on the nature and significance of attachment in infancy and early childhood. We review 4 major topics that are central issues in the scientific literature on attachment: (1) the role of the environment in the development of attachment, (2) the intergenerational transmission of patterns of attachment, (3) the stability of attachment patterns through early adulthood, and (4) the role of attachment in adjustment and maladjustment. We conclude by highlighting several critical unresolved issues and priorities for future research. Copyright © 2017. Published by Elsevier Ltd.

  9. Effects of metric change on safety in the workplace for selected occupations

    NASA Astrophysics Data System (ADS)

    Lefande, J. M.; Pokorney, J. L.

    1982-04-01

    The study assesses the potential safety issues of metric conversion in the workplace. A purposive sample of 35 occupations based on injury and illnesses indexes were assessed. After an analysis of workforce population, hazard analysis and measurement sensitivity of the occupations, jobs were analyzed to identify potential safety hazards by industrial hygienists, safety engineers and academia. The study's major findings were as follows: No metric hazard experience was identified. An increased exposure might occur when particular jobs and their job tasks are going the transition from customary measurement to metric measurement. Well planned metric change programs reduce hazard potential. Metric safety issues are unresolved in the aviation industry.

  10. Coherent versus noncoherent signaling for satellite-aided mobile communications

    NASA Technical Reports Server (NTRS)

    Davarian, F.; Sumida, J.

    1986-01-01

    The use of coherent versus noncoherent communications is an unresolved issue for the mobile satellite community. Should one select the more robust but less efficient noncoherent strategy for communications over satellite-aided mobile channels, or does the introduction of a space platform in the mobile link improve signal stability (both amplitude and phase) such that conventional coherent schemes become attractive? This publication tries to answer some of the questions by discussing the results from experiments using a coherent QPSK receiver. The issues discussed include items such as the measured performance in Rician fading, the link error floor in a fading environment, etc. The results are compared and contrasted with that of a noncoherent limiter/discriminator FM receiver.

  11. From Cases to Capacity? A Critical Reflection on the Role of ‘Ethical Dilemmas’ in the Development of Dual-Use Governance

    PubMed Central

    Edwards, Brett; Revill, James; Bezuidenhout, Louise

    2016-01-01

    The dual-use issue is often framed as a series of paralyzing ‘dilemmas’ facing the scientific community as well as institutions which support innovation. While this conceptualization of the dual-use issue can be useful in certain contexts (such as in awareness-raising and as part of educational activities directed at the scientific community) its usefulness is more limited when reflecting on the governance and politics of the dual-use issue. Within this paper, key shortcomings of the dilemma framing are outlined. It is argued that many of the issues raised in the most recent debates about ‘dual-use’ bird flu research remain unresolved. This includes questions about the trajectories of certain lines of research, as well as broader trends in the practice and governance of science. This leads to difficult questions about current approaches to the dual-use issue within the US, as well as internationally. PMID:23703451

  12. Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design.

    PubMed

    Kelly, Damian J; McCann, Gerald P; Blackman, Daniel; Curzen, Nicholas P; Dalby, Miles; Greenwood, John P; Fairbrother, Kathryn; Shipley, Lorraine; Kelion, Andrew; Heatherington, Simon; Khan, Jamal N; Nazir, Sheraz; Alahmar, Albert; Flather, Marcus; Swanton, Howard; Schofield, Peter; Gunning, Mark; Hall, Roger; Gershlick, Anthony H

    2013-02-22

    Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

  13. Dispersed storage and generation case studies

    NASA Technical Reports Server (NTRS)

    Bahrami, K.; Stallkamp, J. A.; Walton, A.

    1980-01-01

    Three installations utilizing separate dispersed storage and generation (DSG) technologies were investigated. Each of the systems is described in costs and control. Selected institutional and environmental issues are discussed, including life cycle costs. No unresolved technical, environmental, or institutional problems were encountered in the installations. The wind and solar photovoltaic DSG were installed for test purposes, and appear to be presently uneconomical. However, a number of factors are decreasing the cost of DSG relative to conventional alternatives, and an increased DSG penetration level may be expected in the future.

  14. The structural changes in the bone tissue and regional lymph nodes when using bone cement

    NASA Astrophysics Data System (ADS)

    Zhukov, D. V.; Zajdman, A. M.; Prohorenko, V. M.; Ustikova, N. V.

    2017-09-01

    In orthopedics bone cement is used to replace defects. However, it is known that it possesses toxic properties, due to its composition monomer methyl methacrylate. There are some unresolved issues, in particular its local action, not investigated reaction of the immune system to respond to any fluctuations of endoecological equilibrium. All this helps to explain not only the intraoperative complications such as acute heart and lung failure, but also many deferred pathological processes, complications in the postoperative period.

  15. Blueprint for Change: Research on Child and Adolescent Mental Health. Report of the National Advisory Mental Health Council's Workgroup on Child and Adolescent Mental Health Intervention Development and Deployment. Executive Summary and Recommendations.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHHS), Bethesda, MD.

    Much has been learned about the identification and treatment of mental illness in children, but issues remain unresolved. Many of the traditional service models do not meet the needs of today's children. There is a shortage of evidence-based treatment and much of the evidence that does exist is not being used. Key findings in neuroscience,…

  16. DWI at MR Enterography for Evaluating Bowel Inflammation in Crohn Disease.

    PubMed

    Park, Seong Ho

    2016-07-01

    The purpose of this article is to provide a comprehensive review regarding DWI enterography used for evaluating Crohn disease and to summarize the relevant evidence. Active bowel inflammation in Crohn disease causes restricted diffusion on MR enterography with DWI. Enterographic DWI to evaluate Crohn disease is increasingly drawing attention for both academic research and clinical practice and has shown potential as a quantitative tool for assessing bowel inflammation. DWI enterography also has multiple unresolved issues and limitations.

  17. A Review: Advances on Absorption of Heavy Metals in the Waste Water by Biochar

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Xie, Anbin; You, Shaohong

    2018-01-01

    Biochar as a new type of adsorbent, its physical and chemical characteristics and adsorption of heavy metal has been widely studied. Based on the current studies, the article reviewed the main characteristics of biochar, its influencing factors (preparation temperature, feed stocks, functional group et.) on adsorption of heavy metals in water and its mechanism of adsorption (ion exchange adsorption, complexation, precipitation sedimentation et.). Briefly summarize unresolved issues for potential applications of biochar in the future.

  18. Conversion of Low Quality Waste Heat to Electric Power with Small-Scale Organic Rankine Cycle (ORC) Engine/Generator Technology

    DTIC Science & Technology

    2016-06-01

    Allan Robichaux, DPW PWD GTMO and the management and staff of the GTMO on site contractor , Centerra. Page Intentionally Left Blank ii Table of...operations and maintenance contractor to ensure that data transfers are completed as required. Figure 4 shows the location of the ORC installation on MUSE...this issue with telephone support from CRM’s controls contractor (Winn-Marion, W-M); however, the problem remained unresolved as of Sept. 1 when

  19. Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.

    PubMed

    Arrant, Andrew E; Onyilo, Vincent C; Unger, Daniel E; Roberson, Erik D

    2018-02-28

    Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV- Grn ) to deliver progranulin in Grn -/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV- Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV- Grn reduced lipofuscinosis in several brain regions of Grn -/- mice. AAV- Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV- Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV- Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn -/- mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations. SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin ( GRN ) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address several mechanistic questions about the potential of progranulin gene therapy for these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and Grn -/- mouse models develop a similar pathology. AAV-mediated progranulin delivery reduced lipofuscinosis in Grn -/- mice even after the onset of pathology. AAV delivered progranulin only to neurons, not microglia, but improved microgliosis in several brain regions, indicating cross talk between neuronal and microglial pathology. Its beneficial effects were sortilin independent. AAV-derived progranulin was delivered to lysosomes and corrected lysosomal abnormalities. These data provide in vivo support for the efficacy of progranulin-boosting therapies for FTD and NCL. Copyright © 2018 the authors 0270-6474/18/382342-18$15.00/0.

  20. Research Collaboration in a Communication Rights Campaign: Lessons Learned.

    PubMed

    Ryan, Charlotte

    2018-01-01

    In building public support for social change, activists in communities of color routinely approach broader audiences via news media. Communities of color, however, routinely face disparities that limit their access to media including local news media outlets. This lack of access mirrors inequalities in political, social, and economic arenas and can slow public awareness campaigns to address disparities in health, environmental, and other quality-of-life issues. I describe two community-based collaborative action research studies that documented and challenged how local television newscasts underrepresented and misrepresented three communities of color in Boston. The linkage between communication rights and campaigns to address quality-of-life issues is presented, as well as unresolved challenges in the collaborative research process. The study has implications for environmental health campaigns.

  1. Status of thermalhydraulic modelling and assessment: Open issues

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bestion, D.; Barre, F.

    1997-07-01

    This paper presents the status of the physical modelling in present codes used for Nuclear Reactor Thermalhydraulics (TRAC, RELAP 5, CATHARE, ATHLET,...) and attempts to list the unresolved or partially resolved issues. First, the capabilities and limitations of present codes are presented. They are mainly known from a synthesis of the assessment calculations performed for both separate effect tests and integral effect tests. It is also interesting to list all the assumptions and simplifications which were made in the establishment of the system of equations and of the constitutive relations. Many of the present limitations are associated to physical situationsmore » where these assumptions are not valid. Then, recommendations are proposed to extend the capabilities of these codes.« less

  2. X-ray fluorescence microscopy artefacts in elemental maps of topologically complex samples: Analytical observations, simulation and a map correction method

    NASA Astrophysics Data System (ADS)

    Billè, Fulvio; Kourousias, George; Luchinat, Enrico; Kiskinova, Maya; Gianoncelli, Alessandra

    2016-08-01

    XRF spectroscopy is among the most widely used non-destructive techniques for elemental analysis. Despite the known angular dependence of X-ray fluorescence (XRF), topological artefacts remain an unresolved issue when using X-ray micro- or nano-probes. In this work we investigate the origin of the artefacts in XRF imaging of topologically complex samples, which are unresolved problems in studies of organic matter due to the limited travel distances of low energy XRF emission from the light elements. In particular we mapped Human Embryonic Kidney (HEK293T) cells. The exemplary results with biological samples, obtained with a soft X-ray scanning microscope installed at a synchrotron facility were used for testing a mathematical model based on detector response simulations, and for proposing an artefact correction method based on directional derivatives. Despite the peculiar and specific application, the methodology can be easily extended to hard X-rays and to set-ups with multi-array detector systems when the dimensions of surface reliefs are in the order of the probing beam size.

  3. Uncertainty and dispersion in air parcel trajectories near the tropical tropopause

    NASA Astrophysics Data System (ADS)

    Bergman, John; Jensen, Eric; Pfister, Leonhard; Bui, Thoapaul

    2016-04-01

    The Tropical Tropopause Layer (TTL) is important as the gateway to the stratosphere for chemical constituents produced at the Earth's surface. As such, understanding the processes that transport air through the upper tropical troposphere is important for a number of current scientific issues such as the impact of stratospheric water vapor on the global radiative budget and the depletion of ozone by both anthropogenically- and naturally-produced halocarbons. Compared to the lower troposphere, transport in the TTL is relatively unaffected by turbulent motion. Consequently, Lagrangian particle models are thought to provide reasonable estimates of parcel pathways through the TTL. However, there are complications that make trajectory analyses difficult to interpret; uncertainty in the wind data used to drive these calculations and trajectory dispersion being among the most important. These issues are examined using ensembles of backward air parcel trajectories that are initially tightly grouped near the tropical tropopause using three approaches: A Monte Carlo ensemble, in which different members use identical resolved wind fluctuations but different realizations of stochastic, multi-fractal simulations of unresolved winds, perturbed initial location ensembles, in which members use identical resolved wind fields but initial locations are displaced 2° in latitude and longitude, and a multi-model ensemble that uses identical initial conditions but different resolved wind fields and/or trajectory formulations. Comparisons among the approaches distinguish, to some degree, physical dispersion from that due to data uncertainty and the impact of unresolved wind fluctuations from that of resolved variability.

  4. How does disclosing countertransference affect perceptions of the therapist and the session?

    PubMed

    Yeh, Yun-Jy; Hayes, Jeffrey A

    2011-12-01

    Therapist self-disclosure has been theorized and found to have both positive and negative effects. These effects depend, in part, on the nature of the disclosure. This study sought to examine the differential effects of therapist disclosures of more and less resolved countertransference issues on perceptions of therapists and therapy sessions. Using an analogue method, undergraduate participants (N = 116) were randomly assigned to watch one of two videos in which a therapist disclosed personal issues that were relatively resolved or relatively unresolved. As hypothesized, therapist disclosure of issues that were more resolved caused the therapist to be rated as more attractive and trustworthy and instilled greater hope than therapist disclosure of less resolved issues. The type of therapist disclosure, however, did not affect ratings of the expertness of the therapist, the depth or smoothness of the session, or the perceived universality between client and therapist. Implications of the results for the judicious use of self-disclosure are discussed.

  5. Current issues relating to psychosocial job strain and cardiovascular disease research.

    PubMed

    Theorell, T; Karasek, R A

    1996-01-01

    The authors comment on recent reviews of cardiovascular job strain research by P. L. Schnall and P. A. Landsbergis (1994), and by T. S. Kristensen (1995), which conclude that job strain as defined by the demand-control model (the combination of contributions of low job decision latitudes and high psychological job demands) is confirmed as a risk factor for cardiovascular mortality in a large majority of studies. Lack of social support at work appears to further increase risk. Several still-unresolved research questions are examined in light of recent studies: (a) methodological issues related to use of occupational aggregate estimations and occupational career aggregate assessments, use of standard scales for job analysis and recall bias issues in self-reporting; (b) confounding factors and differential strengths of association by subgroups in job strain-cardiovascular disease analyses with respect to social class, gender, and working hours; and (c) review of results of monitoring job strain-blood pressure associations and associated methodological issues.

  6. Ethical and Clinical Considerations at the Intersection of Functional Neuroimaging and Disorders of Consciousness.

    PubMed

    Byram, Adrian C; Lee, Grace; Owen, Adrian M; Ribary, Urs; Stoessl, A Jon; Townson, Andrea; Illes, Judy

    2016-10-01

    Recent neuroimaging research on disorders of consciousness provides direct evidence of covert consciousness otherwise not detected clinically in a subset of severely brain-injured patients. These findings have motivated strategic development of binary communication paradigms, from which researchers interpret voluntary modulations in brain activity to glean information about patients' residual cognitive functions and emotions. The discovery of such responsiveness raises ethical and legal issues concerning the exercise of autonomy and capacity for decisionmaking on matters such as healthcare, involvement in research, and end of life. These advances have generated demands for access to the technology against a complex background of continued scientific advancement, questions about just allocation of healthcare resources, and unresolved legal issues. Interviews with professionals whose work is relevant to patients with disorders of consciousness reveal priorities concerning further basic research, legal and policy issues, and clinical considerations.

  7. Addendum report to atmospheric science facility pallet-only mode space transportation system payload feasibility study, volume 3, revision A

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The feasibility of accomplishing selected atmospheric science mission using a pallet-only mode was studied. Certain unresolved issues were identified. The first issue was that of assuring that the on-board computer facility was adequate to process scientific data, control subsystems such as instrument pointing, provide mission operational program capability, and accomplish display and control. The second issue evolved from an investigation of the availability of existing substitute instruments that could be used instead of the prime instrumentation where the development tests and schedules are incompatible with the realistic budgets and shuttle vehicle schedules. Some effort was expended on identifying candidate substitute instruments, and the performance, cost, and development schedule trade-offs found during that effort were significant enough to warrant a follow-on investigation. This addendum documents the results of that follow-on effort, as it applies to the Atmospheric Sciences Facility.

  8. Patterns of Drug Distribution: Implications and Issues#

    PubMed Central

    Johnson, Bruce D.

    2007-01-01

    This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years, including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for “drug abuse” to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues. PMID:14582578

  9. Patterns of drug distribution: implications and issues.

    PubMed

    Johnson, Bruce D

    2003-01-01

    This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years. including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for "drug abuse" to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues.

  10. Chronic hyperkalemia in non-dialysis CKD: controversial issues in nephrology practice.

    PubMed

    De Nicola, Luca; Di Lullo, Luca; Paoletti, Ernesto; Cupisti, Adamasco; Bianchi, Stefano

    2018-06-07

    Chronic hyperkalemia is a major complication of chronic kidney disease (CKD) that occurs frequently, heralds poor prognosis, and necessitates careful management by the nephrologist. Current strategies aimed at prevention and treatment of hyperkalemia are still suboptimal, as evidenced by the relatively high prevalence of hyperkalemia in patients under stable nephrology care, and even in the ideal setting of randomized trials where best treatment and monitoring are mandatory. The aim of this review was to identify and discuss a range of unresolved issues related to the management of chronic hyperkalemia in non-dialysis CKD. The following topics of clinical interest were addressed: diagnosis, relationship with main comorbidities of CKD, therapy with inhibitors of the renin-angiotensin-aldosterone system, efficacy of current dietary and pharmacological treatment, and the potential role of the new generation of potassium binders. Opinion-based answers are provided for each of these controversial issues.

  11. Some critical issues and concerns related to research advances on toxicology of chemical mixtures.

    PubMed Central

    Yang, R S

    1998-01-01

    This paper addresses some of the issues and concerns on research advances on the toxicology of chemical mixtures. Emphases will be selectively given to the following questions and answers: Can mechanistic studies be conducted on chemical mixtures? The fact that any studies, including mechanistic studies, of single chemicals are really the study of the parent chemical plus its metabolites underscores the relevance of mechanistic studies on chemical mixtures. Can predictions be made on the health effects of chemical mixtures? Some successes are already evident in the literature on simpler chemical mixtures. For more complex mixtures, it is possible and we propose an approach here. What can we learn from other disciplines (the importance of interdisciplinary collaboration)? Two aspects, the knowledge and methodologies available in clinical pharmacology and the latest advances in structure-oriented lumping in chemical engineering, are discussed in detail. Unrepeatable results: The possibility of magnification of biologic variability because of low-level exposures to chemical mixtures is suggested with special reference to some known examples, including the controversial study on synergistic interactions of endocrine disruptors. Is the driving force for scientific investigations on chemical mixtures the legislative and regulatory atmosphere? Two laws with chemical mixtures specifically in the language are quoted and discussed. Their implications regarding research funding and activities are described. What are the pitfalls of applying for research funding on investigating chemical mixtures? The dilemma at least one investigator faces in pursuing research funding is elaborated. The questions and issues listed above are not all inclusive, but they represent some of the aspects that need to be brought into the open in the scientific community for discussion and/or debate. Thus, the primary objective of this paper is to provide some momentum for the beginning of a fruitful and stimulating discussion. PMID:9703493

  12. Improving Interpretation of New and Old Serum Biomarkers of Drug-Induced Liver Injury Through Mechanistic Modeling.

    PubMed

    Watkins, Paul B

    2018-04-26

    The study by Mason et al. in this issue used mechanistic modeling and simulation to address how both the dose of acetaminophen consumed and the time since ingestion can be estimated from biomarkers measured in a single serum sample in mice. Translation into the clinic would potentially be an advance in the treatment of acetaminophen poisoning. Importantly, this approach could transform the evaluation of liver safety in clinical trials of new drug candidates. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  13. Treatment of anemia in chronic kidney disease: known, unknown, and both.

    PubMed

    Foley, Robert N

    2011-01-01

    Erythropoiesis is a rapidly evolving research arena and several mechanistic insights show therapeutic promise. In contrast with the rapid advance of mechanistic science, optimal management of anemia in patients with chronic kidney disease remains a difficult and polarizing issue. Although several large hemoglobin target trials have been performed, optimal treatment targets remain elusive, because none of the large trials to date have unequivocally identified differences in primary outcome rates or death rates, and because other reported outcomes indicate the potential for harm (rates of stroke, early requirement for dialysis, and vascular access thrombosis) and benefit (reductions in transfusion requirements and fatigue).

  14. From Unresolved Anger to Sadness: Identifying Physiological Correlates

    ERIC Educational Resources Information Center

    Rochman, Daniel; Diamond, Gary M.

    2008-01-01

    This study was designed to identify physiological correlates of unresolved anger and sadness, and the shift between these emotions, in a context similar to that of emotion-focused, experiential psychotherapy. Twenty-seven university students reporting unresolved anger toward an attachment figure were induced to experience and express unresolved…

  15. A Structural Approach to Unresolved Mourning in Single Parent Family Systems.

    ERIC Educational Resources Information Center

    Fulmer, Richard H.

    1983-01-01

    Considers the mother's depression as a special problem in therapy of single-parent families, resulting from unresolved mourning maintained by the family system. Offers reasons why the single-parent family's structure seems inherently vulnerable to unresolved mourning. Suggests techniques of Structural Family Therapy to facilitate mourning in such…

  16. What do consumer surveys and experiments reveal and conceal about consumer preferences for genetically modified foods?

    PubMed

    Colson, Gregory; Rousu, Matthew C

    2013-01-01

    Assessing consumer perceptions and willingness to pay for genetically modified (GM) foods has been one of the most active areas of empirical research in agricultural economics. Researchers over the past 15 years have delivered well over 100 estimates of consumers' willingness to pay for GM foods using surveys and experimental methods. In this review, we explore a number of unresolved issues related to three questions that are critical when considering the sum of the individual contributions that constitute the evidence on consumer preferences for GM foods.

  17. The ethics of human gene transfer.

    PubMed

    Kimmelman, Jonathan

    2008-03-01

    Almost 20 years since the first gene-transfer trial was carried out in humans, the field has made significant advances towards clinical application. Nevertheless, it continues to face numerous unresolved ethical challenges--among them are the question of when to initiate human testing, the acceptability of germline modification and whether the technique should be applied to the enhancement of traits. Although such issues have precedents in other medical contexts, they take on a different character in gene transfer, in part because of the scientific uncertainty and the social context of innovation.

  18. The Most Critical Unresolved Issues Associated with Race, Ethnicity, Culture, and Substance Use

    PubMed Central

    Unger, Jennifer B.

    2015-01-01

    This paper discusses the limitations of previous research on race, ethnicity, culture, and substance use. The study offers the following recommendations for future research in this area: (1) move beyond simple comparisons of mutually exclusive groups, (2) focus on the meaning of an ethnic label to the individual, (3) consider the complex interactions between an individual’s cultural identity and the cultural context, (4) understand and acknowledge the researcher’s inherent biases, and (5) translate research findings into practice and policy change. PMID:22217334

  19. Patchwork plagiarism--a jigsaw of stolen puzzle pieces.

    PubMed

    Supak Smolcić, Vesna; Bilić-Zulle, Lidija

    2013-01-01

    Plagiarism remains at the top in terms of interest to the scientific community. In its many vicious forms, patchwork plagiarism is characterized by numerous unresolved issues and often passes "below the radar" of editors and reviewers. The problem of detecting the complexity of misconduct has been partially resolved by plagiarism detection software. However, interpretation of relevant reports is not always obvious or easy. This article deals with plagiarism in general and patchwork plagiarism in particular, as well as related problems that editors must deal with to maintain the integrity of scientific journals.

  20. Archetype and object: primary deintegration and primary love in analytical play therapy with young children.

    PubMed

    Peery, J Craig

    2002-07-01

    Jungian and post-Jungian theory of the development of the child's psyche is reviewed. A discrimination between primary and secondary deintegration is suggested. Post-Freudian theory regarding primary object relations is integrated with the Jungian model. The two approaches can contribute synergistically to inform and advance play therapy with young children. Patients from widely diverse cultural backgrounds use their relationship with the therapist as a helpful person (object), and engage in archetypal material from the collective unconscious, to help them work on and through their unresolved emotional issues.

  1. [Transanal total mesorectal excision for rectal cancer - just a fashion trend?].

    PubMed

    Kala, Z; Skrovina, M; Procházka, V; Grolich, T; Klos, K

    2014-12-01

    Transanal total mesorectal excision performed using equipment for transanal minimally invasive surgery is an innovative surgical technique introduced to facilitate this procedure and to reach better oncosurgical outcomes in patients with low rectal cancer. This article presents a brief summary of guidelines for treatment of patients with low rectal carcinoma. Up-to-date information about the principles of this new method, its modifications and contemporary indications is presented. Based on their own experience and literature resources, the authors inform about the advantages, limitations and unresolved issues of minimally invasive transanal mesorectal excision.

  2. The pulmonary physician in critical care * 4: Nosocomial pneumonia.

    PubMed

    Ewig, S; Bauer, T; Torres, A

    2002-04-01

    Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved. The controversy over diagnostic tools should be closed. Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm. More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention.

  3. Analyses of group sequential clinical trials.

    PubMed

    Koepcke, W

    1989-12-01

    In the first part of this article the methodology of group sequential plans is reviewed. After introducing the basic definition of such plans the main properties are shown. At the end of this section three different plans (Pocock, O'Brien-Fleming, Koepcke) are compared. In the second part of the article some unresolved issues and recent developments in the application of group sequential methods to long-term controlled clinical trials are discussed. These include deviation from the assumptions, life table methods, multiple-arm clinical trials, multiple outcome measures, and confidence intervals.

  4. Change in attachment states of mind of women with binge-eating disorder.

    PubMed

    Maxwell, Hilary; Tasca, Giorgio A; Grenon, Renee; Ritchie, Kerri; Bissada, Hany; Balfour, Louise

    2017-11-01

    Insecure and unresolved/disorganized attachment states of mind may impact affect regulation and interpersonal functioning that contribute to binge eating in women with binge-eating disorder (BED). Group psychological treatment may facilitate changes from insecure to secure and from unresolved-disorganized to non-unresolved/disorganized attachment states of mind. This study used attachment theory to understand better the psychopathology of BED and co-morbid overweight status and to understand better the treatment response of patients with BED who receive group psychotherapy. Women with BED attended group psychodynamic interpersonal psychotherapy and completed the Adult Attachment Interview pretreatment and 6 months posttreatment. Matched samples of overweight women without BED and normal-weight women without BED completed the Adult Attachment Interview at 1 time point. Women with BED had significantly higher rates of preoccupied and unresolved/disorganized attachment states of mind compared to normal-weight women without BED and had similar rates of insecure and unresolved/disorganized attachment states of mind compared to overweight women without BED. Of the women with BED who had an insecure and/or unresolved/disorganized attachment states of mind at pretreatment, about 60% demonstrated clinically relevant changes to secure and to non-unresolved/disorganized states of mind at 6 months post group psychodynamic interpersonal psychotherapy. Results indicated that some women with BED may benefit from interventions that help them regulate hyperactivated affect and create coherent narratives. Both women with BED and overweight women without BED may benefit from treatments that help them develop more adaptive affect regulation strategies related to unresolved/disorganized attachment states of mind. Copyright © 2017 John Wiley & Sons, Ltd.

  5. 77 FR 42788 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Unresolved Account Balances in the Exchange's Online Comparison System July 16, 2012. Pursuant to Section 19... assigning the contra party to unresolved account balances in the Exchange's Online Comparison System. The... maker (``DMM'') unit as the contra party for any unresolved omnibus account balances in the Exchange's...

  6. From the exposome to mechanistic understanding of chemical-induced adverse effects

    EPA Science Inventory

    BACKGROUND: Current definitions of the exposome expand beyond the initial idea to consider the totality of exposure and aim to relate to biological effects. While the exposome has been established for human health, its principles can be extended to include broader ecological issu...

  7. ARSENIC: CARCINOGENIC MECHANISMS, RISK ASSESSMENT AND THE MAXIMUM CONTAMINANT LEVEL (MCL)

    EPA Science Inventory


    This workshop will provide an up-to-date overview on key issues related to cancer risk assessment of arsenic: carcinogenic mechanisms; application of mechanistic information to risk assessment models; and the development of the MCL for arsenic in drinking water. The two prese...

  8. Wireless shared resources : sharing right-of-way for wireless telecommunications : guidance on legal and institutional issues

    DOT National Transportation Integrated Search

    1998-04-01

    The study reported here was conducted to assess how well some of the existing asphalt pavement mechanistic-empirical distress prediction models performed when used in conjunction with the data being collected as part of the national Long Term Pavemen...

  9. Precision about the automatic emotional brain.

    PubMed

    Vuilleumier, Patrik

    2015-01-01

    The question of automaticity in emotion processing has been debated under different perspectives in recent years. Satisfying answers to this issue will require a better definition of automaticity in terms of relevant behavioral phenomena, ecological conditions of occurrence, and a more precise mechanistic account of the underlying neural circuits.

  10. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    PubMed Central

    Rajshekhar, Vedantam

    2016-01-01

    Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

  11. How couples manage interracial and intercultural differences: implications for clinical practice.

    PubMed

    Seshadri, Gita; Knudson-Martin, Carmen

    2013-01-01

    This study focused on how couples managed their interracial and intercultural differences. To understand their experiences, a qualitative grounded theory analysis was used (n=17). Analysis revealed that couples experienced most issues as cultural issues; race only occurred during their interactions with "others." They appeared to organize their responses according to four relationship structures: Integrated, Singularly Assimilated, Coexisting, and Unresolved. Couples in each of these structures managed daily process through four sets of relationship strategies: (a) creating a "we," (b) framing differences, (c) emotional maintenance, and (d) positioning in relationship to familial and societal context. These findings are a step toward a strength-based and research-informed education and clinical interventions for this population. Video Abstract. © 2012 American Association for Marriage and Family Therapy.

  12. The patient who believes and the analyst who does not (1).

    PubMed

    Lijtmaer, Ruth M

    2009-01-01

    A patient's religious beliefs and practices challenge the clinical experience and self-knowledge of the analyst owing to a great complexity of factors, and often take the form of the analyst's resistances and countertransference reactions to spiritual and religious issues. The analyst's feelings about the patient's encounters with religion and other forms of healing experiences may result in impasses and communication breakdown for a variety of reasons. These reasons include the analyst's own unresolved issues around her role as a psychoanalyst-which incorporates in some way psychoanalysis's views of religious belief-and these old conflicts may be irritated by the religious themes expressed by the patient. Vignettes from the treatments of two patients provide examples of the analyst's countertransference conflicts, particularly envy in the case of a therapist who is an atheist.

  13. Status, sale and patenting of human genetic material: an international survey.

    PubMed

    Knoppers, B M

    1999-05-01

    Following a decade of debate, the European Directive on the Legal Protection of Biotechnological Inventions was adopted by the European Parliament and the Council of the European Union on July 6, 1998. The Directive constitutes a legal and social policy landmark in biotechnology, taking an explicit position on the contentious issue of the patentability of higher life forms. It fails, however, to provide definitive statements on the legal status of human genetic material or the possibility of personal financial gain in relation to such material. An overview of the international, regional and national positions (as found in laws and official policy statements) on the status, commodification and patentability of human genetic material indicates that, although the Directive represents a consolidation of opinions, many issues remain unresolved.

  14. [Empowerment and health promotion programming].

    PubMed

    Laverack, G

    2008-12-01

    Health promotion often presents a tension between "bottom up" and "top down" programming. "Bottom-up" is associated with community empowerment and begins on issues of concern to particular groups or individuals and regards an increase in overall control as an important element of the health outcome. "Top-down" is associated with disease prevention efforts and begins by seeking to involve beneficiaries on issues defined by health agencies. It regards improvements in health behaviours or bio-medical indicators as the important outcome and community empowerment is viewed simply as a means to the end of health behaviour change. The tension between these two approaches is not unresolvable, and this article presents a framework, the "parallel-track", intended to assist health promotion practitioners to systematically accommodate community empowerment goals within "top-down" health programming.

  15. Perception of the pitch of unresolved harmonics by 3- and 7-month-old human infants.

    PubMed

    Lau, Bonnie K; Werner, Lynne A

    2014-08-01

    Three-month-olds discriminate resolved harmonic complexes on the basis of missing fundamental (MF) pitch. In view of reported difficulty in discriminating unresolved complexes at 7 months and striking changes in the organization of the auditory system during early infancy, infants' ability to discriminate unresolved complexes is of some interest. This study investigated the ability of 3-month-olds, 7-month-olds, and adults to discriminate the pitch of unresolved harmonic complexes using an observer-based method. Stimuli were MF complexes bandpass filtered with a -12 dB/octave slope, combined in random phase, presented at 70 dB sound pressure level (SPL) for 650 ms with a 50 ms rise/fall with a pink noise at 65 dB SPL. The conditions were (1) "LOW" unresolved harmonics (2500-4500 Hz) based on MFs of 160 and 200 Hz and (2) "HIGH" unresolved harmonics (4000-6000 Hz) based on MFs of 190 and 200 Hz. To demonstrate MF discrimination, participants had to ignore spectral changes in complexes with the same fundamental and respond only when the fundamental changed. Nearly all infants tested categorized complexes by MF pitch suggesting discrimination of pitch extracted from unresolved harmonics by 3 months. Adults also categorized the complexes by MF pitch, although musically trained adults were more successful than musically untrained adults.

  16. A rule-based expert system for chemical prioritization using effects-based chemical categories

    EPA Science Inventory

    A rule-based expert system (ES) was developed to predict chemical binding to the estrogen receptor (ER) patterned on the research approaches championed by Gilman Veith to whom this article and journal issue are dedicated. The ERES was built to be mechanistically-transparent and m...

  17. Two (Very) Different Worlds: The Cultures of Policymaking and Qualitative Research

    ERIC Educational Resources Information Center

    Donmoyer, Robert

    2012-01-01

    This article brackets assumptions embedded in the framing of this special issue on "problematizing methodological simplicity in qualitative research" in a effort to understand why policymakers put pressure on all types of researchers, including those who use qualitative methods, to provide relatively simple, even somewhat mechanistic portrayals of…

  18. Lipid Catabolism Fuels Drosophila Gut Immunity.

    PubMed

    Masuzzo, Ambra; Royet, Julien

    2018-03-14

    Immune responses and metabolic regulation are tightly coupled in animals, but the underlying mechanistic connections are not fully understood. In this issue of Cell Host & Microbe, Lee et al. (2018) reveal how sustained ROS production in the gut depends on an upstream metabolic switch. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Is the time right for quantitative public health guidelines on sitting? A narrative review of sedentary behaviour research paradigms and findings.

    PubMed

    Stamatakis, Emmanuel; Ekelund, Ulf; Ding, Ding; Hamer, Mark; Bauman, Adrian E; Lee, I-Min

    2018-06-10

    Sedentary behaviour (SB) has been proposed as an 'independent' risk factor for chronic disease risk, attracting much research and media attention. Many countries have included generic, non-quantitative reductions in SB in their public health guidelines and calls for quantitative SB targets are increasing. The aim of this narrative review is to critically evaluate key evidence areas relating to the development of guidance on sitting for adults. We carried out a non-systematic narrative evidence synthesis across seven key areas: (1) definition of SB, (2) independence of sitting from physical activity, (3) use of television viewing as a proxy of sitting, (4) interpretation of SB evidence, (5) evidence on 'sedentary breaks', (6) evidence on objectively measured sedentary SB and mortality and (7) dose response of sitting and mortality/cardiovascular disease. Despite research progress, we still know little about the independent detrimental health effects of sitting, and the possibility that sitting is mostly the inverse of physical activity remains. Unresolved issues include an unclear definition, inconsistencies between mechanistic and epidemiological studies, over-reliance on surrogate outcomes, a very weak epidemiological evidence base to support the inclusion of 'sedentary breaks' in guidelines, reliance on self-reported sitting measures, and misinterpretation of data whereby methodologically inconsistent associations are claimed to be strong evidence. In conclusion, public health guidance requires a consistent evidence base but this is lacking for SB. The development of quantitative SB guidance, using an underdeveloped evidence base, is premature; any further recommendations for sedentary behaviour require development of the evidence base and refinement of the research paradigms used in the field. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Components of the Extragalactic Gamma-Ray Background

    NASA Technical Reports Server (NTRS)

    Stecker, Floyd W.; Venters, Tonia M.

    2011-01-01

    We present new theoretical estimates of the relative contributions of unresolved blazars and star-forming galaxies to the extragalactic gamma-ray background (EGB) and discuss constraints on the contributions from alternative mechanisms such as dark matter annihilation and truly diffuse gamma-ray production. We find that the Fermi source count data do not rule out a scenario in which the EGB is dominated by emission from unresolved blazars, though unresolved star-forming galaxies may also contribute significantly to the background, within order-of-magnitude uncertainties. In addition, we find that the spectrum of the unresolved star-forming galaxy contribution cannot explain the EGB spectrum found by EGRET at energies between 50 and 200 MeV, whereas the spectrum of unresolved flat spectrum radio quasars, when accounting for the energy-dependent effects of source confusion, could be consistent with the combined spectrum of the low-energy EGRET EGB measurements and the Fermi-Large Area Telescope EGB measurements.

  1. Comparing the incomparable? A systematic review of competing techniques for converting descriptive measures of health status into QALY-weights.

    PubMed

    Mortimer, Duncan; Segal, Leonie

    2008-01-01

    Algorithms for converting descriptive measures of health status into quality-adjusted life year (QALY)--weights are now widely available, and their application in economic evaluation is increasingly commonplace. The objective of this study is to describe and compare existing conversion algorithms and to highlight issues bearing on the derivation and interpretation of the QALY-weights so obtained. Systematic review of algorithms for converting descriptive measures of health status into QALY-weights. The review identified a substantial body of literature comprising 46 derivation studies and 16 studies that provided evidence or commentary on the validity of conversion algorithms. Conversion algorithms were derived using 1 of 4 techniques: 1) transfer to utility regression, 2) response mapping, 3) effect size translation, and 4) "revaluing" outcome measures using preference-based scaling techniques. Although these techniques differ in their methodological/theoretical tradition, data requirements, and ease of derivation and application, the available evidence suggests that the sensitivity and validity of derived QALY-weights may be more dependent on the coverage and sensitivity of measures and the disease area/patient group under evaluation than on the technique used in derivation. Despite the recent proliferation of conversion algorithms, a number of questions bearing on the derivation and interpretation of derived QALY-weights remain unresolved. These unresolved issues suggest directions for future research in this area. In the meantime, analysts seeking guidance in selecting derived QALY-weights should consider the validity and feasibility of each conversion algorithm in the disease area and patient group under evaluation rather than restricting their choice to weights from a particular derivation technique.

  2. Global-scale Ionospheric Outflow: Major Processes and Unresolved Problems

    NASA Astrophysics Data System (ADS)

    Liemohn, M. W.; Welling, D. T.; Ilie, R.; Khazanov, G. V.; Jahn, J. M.; Zou, S.; Ganushkina, N. Y.; Valek, P. W.; Elliott, H. A.; Gilchrist, B. E.; Hoegy, W. R.; Glocer, A.

    2016-12-01

    Outflow from the ionosphere is a major source of plasma to the magnetosphere. Its presence, especially that of ions heavier than He+, mass loads the magnetosphere and changes reconnection rates, current system configurations, plasma wave excitation and wave-particle interactions. It even impacts the propagation of information. We present a brief overview of the major processes and scientific history of this field. There are still major gaps, however, in our understanding of the global-scale nature of ionospheric outflow. We discuss these unresolved problems highlighting the leading questions still outstanding on this topic. First and foremost, since the measurements of ionospheric outflow have largely come from individual satellites and sounding rockets, the processes are best known on the local level, while the spatial distribution of outflow has never been simultaneously measured on more global scales. The spatial coherence and correlation of outflow across time and space have not been quantified. Furthermore, the composition of the outflow is often only measured at a coarse level of H+, He+, and O+, neglecting other species such as N+ or moleculars. However, resolving O+ from N+, as is customary in planetary research, aids in revealing the physics and altitude dependence of the energization processes in the ionosphere. Similarly, fine-resolution velocity space measurements of ionospheric outflow have been limited, yet such observations can also reveal energization processes driving the outflow. A final unresolved issue to mention is magnetically conjugate outflow and the full extent of hemispherically asymmetric outflow fluxes or fluence. Each of these open questions have substantial ramifications for magnetospheric physics; their resolution could yield sweeping changes in our understanding of nonlinear feedback and cross-scale physical interactions, magnetosphere-ionosphere coupling, and geospace system-level science.

  3. From the exposome to mechanistic understanding of chemical ...

    EPA Pesticide Factsheets

    BACKGROUND: Current definitions of the exposome expand beyond the initial idea to consider the totality of exposure and aim to relate to biological effects. While the exposome has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. OBJECTIVES: We explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept - a framework to structure and organize the sequence of toxicological events from an initial molecular interaction of a chemical to an adverse outcome.METHODS: This review was informed by a Workshop organized by the Integrated Project EXPOSOME at the UFZ Helmholtz Centre for Environmental Research in Leipzig, Germany. DISCUSSION: The exposome encompasses all chemicals, including exogenous chemicals and endogenous compounds that are produced in response to external factors. By complementing the exposome research with the AOP concept, we can achieve a better mechanistic understanding, weigh the importance of various components of the exposome, and determine primary risk drivers. The ability to interpret multiple exposures and mixture effects at the mechanistic level requires a more holistic approach facilitated by the exposome concept.CONCLUSION: Incorporating the AOP conc

  4. The Public/Private Partnership behind the Cash and Counseling Demonstration and Evaluation: Its Origins, Challenges, and Unresolved Issues

    PubMed Central

    Knickman, James R; Stone, Robyn I

    2007-01-01

    objective To discuss why and how the Cash and Counseling Demonstration came to be designed, implemented, and evaluated through a partnership between the U.S. Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation (ASPE) and the Robert Wood Johnson Foundation (RWJF). Principal Findings This public/private partnership was created by two colleagues who were motivated by the need for funding to conduct a large-scale demonstration and evaluation, the prestige that both organizations brought to the project, the ability to draw on both organizations' experience and expertise, and the potential to maximize flexibility in the design and implementation of the demonstration. The partnership, which has lasted over a decade and has supported two generations of Cash and Counseling programs, overcame several challenges including getting approval for the project through their respective bureaucracies, managing the decision making process and the ongoing program across the two organizations, dealing with leadership and staff turnover, and reaching consensus on how to apportion credit for the success of the program. Several unresolved issues remain, including how the program gets operationalized within each state, how case management is addressed within the context of a consumer-directed model like Cash and Counseling, how quality is assured in this type of program, and how the Internal Revenue Service views and treats Cash and Counseling and other consumer-directed programs. Conclusion This public/private partnership is an illustration of how public dollars can be leveraged effectively to examine a pressing policy issue and to produce information that can be translated into better policy and practice. The ASPE/RWJF collaboration made it possible to develop, test, and expand a policy-oriented demonstration project that has become a pivotal strategy in most states' efforts to build their home and community-based service systems. PMID:17244288

  5. Human Health Effects of Biphenyl: Key Findings and Scientific Issues.

    PubMed

    Li, Zheng; Hogan, Karen A; Cai, Christine; Rieth, Susan

    2016-06-01

    In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. We review key findings and scientific issues regarding expected human health effects of biphenyl. Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703-712; http://dx.doi.org/10.1289/ehp.1509730.

  6. Personal Health, Person-centred Health and Personalised Medicine - Concepts, Consumers, Confusion and Challenges in the Informatics World.

    PubMed

    Rigby, M

    2012-01-01

    To define and assess 'Consumer Health Informatics' and related emergent issues in an era of new media and of personalisation of care, and from this to define what actions need to be taken to optimise benefits and address risks. Definition of key concepts; review of health personalisation, emergent health information and communication technologies and knowledge sources available to citizens and social media; and identification of unresolved issues threatening optimal use of each. A structured review supported by citations and examples. Several new aspects of consumer health informatics are emerging, including new knowledge sources, feedback on treatments and care providers, on-line videos, and a new generation of patient experience sites including those which are for profit and seek to influence treatment paradigms. Not just the information usage, but also the potential social challenges and malicious abuses, are global issues, and also transcend the traditional health community and thus should be addressed in partnership with other global agencies.

  7. Vertebrate Reservoirs of Arboviruses: Myth, Synonym of Amplifier, or Reality?

    PubMed Central

    Kuno, Goro; Mackenzie, John S.; Plyusnin, Alexander; Gubler, Duane J.

    2017-01-01

    The rapid succession of the pandemic of arbovirus diseases, such as dengue, West Nile fever, chikungunya, and Zika fever, has intensified research on these and other arbovirus diseases worldwide. Investigating the unique mode of vector-borne transmission requires a clear understanding of the roles of vertebrates. One major obstacle to this understanding is the ambiguity of the arbovirus definition originally established by the World Health Organization. The paucity of pertinent information on arbovirus transmission at the time contributed to the notion that vertebrates played the role of reservoir in the arbovirus transmission cycle. Because this notion is a salient feature of the arbovirus definition, it is important to reexamine its validity. This review addresses controversial issues concerning vertebrate reservoirs and their role in arbovirus persistence in nature, examines the genesis of the problem from a historical perspective, discusses various unresolved issues from multiple points of view, assesses the present status of the notion in light of current knowledge, and provides options for a solution to resolve the issue. PMID:28703771

  8. Vertebrate Reservoirs of Arboviruses: Myth, Synonym of Amplifier, or Reality?

    PubMed

    Kuno, Goro; Mackenzie, John S; Junglen, Sandra; Hubálek, Zdeněk; Plyusnin, Alexander; Gubler, Duane J

    2017-07-13

    The rapid succession of the pandemic of arbovirus diseases, such as dengue, West Nile fever, chikungunya, and Zika fever, has intensified research on these and other arbovirus diseases worldwide. Investigating the unique mode of vector-borne transmission requires a clear understanding of the roles of vertebrates. One major obstacle to this understanding is the ambiguity of the arbovirus definition originally established by the World Health Organization. The paucity of pertinent information on arbovirus transmission at the time contributed to the notion that vertebrates played the role of reservoir in the arbovirus transmission cycle. Because this notion is a salient feature of the arbovirus definition, it is important to reexamine its validity. This review addresses controversial issues concerning vertebrate reservoirs and their role in arbovirus persistence in nature, examines the genesis of the problem from a historical perspective, discusses various unresolved issues from multiple points of view, assesses the present status of the notion in light of current knowledge, and provides options for a solution to resolve the issue.

  9. Conflict management: a primer for doctors in training.

    PubMed

    Saltman, D C; O'Dea, N A; Kidd, M R

    2006-01-01

    Conflict in the health arena is a growing concern and is well recognised for doctors in training. Its most extreme expression, workplace violence is on the increase. There is evidence that many conflicts remain unsatisfactorily resolved or unresolved, and result in ongoing issues for staff morale. This paper describes the nature of conflict in the health care system and identifies the difference between conflict and disagreement. Using a conflict resolution model, strategies for dealing with conflict as it arises are explored and tips are provided on how to effectively manage conflict to a satisfactory resolution for all parties.

  10. Advances in molecular-based diagnostics in meeting crop biosecurity and phytosanitary issues.

    PubMed

    Schaad, Norman W; Frederick, Reid D; Shaw, Joe; Schneider, William L; Hickson, Robert; Petrillo, Michael D; Luster, Douglas G

    2003-01-01

    Awareness of crop biosecurity and phytosanitation has been heightened since 9/11 and the unresolved anthrax releases in October 2001. Crops are highly vulnerable to accidental or deliberate introductions of crop pathogens from outside U.S. borders. Strategic thinking about protection against deliberate or accidental release of a plant pathogen is an urgent priority. Rapid detection will be the key to success. This review summarizes recent progress in the development of rapid real-time PCR protocols and evaluates their effectiveness in a proposed nationwide network of diagnostic laboratories that will facilitate rapid diagnostics and improved communication.

  11. Neutron star binaries, pulsars and burst sources

    NASA Technical Reports Server (NTRS)

    Lamb, F. K.

    1981-01-01

    Unresolved issues involving neutron star binaries, pulsars, and burst sources are described. Attention is drawn to the types of observations most likely to resolve them. Many of these observations are likely to be carried out during the next decade by one or more missions that have been approved or proposed. Flux measurements with an imaging detector and broad-band spectroscopic studies in the energy range 30-150 keV are discussed. The need for soft X-ray and X-ray observations with an instrument which has arcminute angular resolution and an effective area substantially greater than of ROSAT or EXOSAT is also discussed.

  12. The cognitive neuroscience of ageing.

    PubMed

    Grady, Cheryl

    2012-06-20

    The availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive ageing. Although there is a growing consensus that the ageing brain retains considerable plasticity of function, currently measured primarily by means of functional MRI, it is less clear how age differences in brain activity relate to cognitive performance. The field is also hampered by the complexity of the ageing process itself and the large number of factors that are influenced by age. In this Review, current trends and unresolved issues in the cognitive neuroscience of ageing are discussed.

  13. Patchwork plagiarism – a jigsaw of stolen puzzle pieces

    PubMed Central

    Smolčić, Vesna Šupak; Bilić-Zulle, Lidija

    2013-01-01

    Plagiarism remains at the top in terms of interest to the scientific community. In its many vicious forms, patchwork plagiarism is characterized by numerous unresolved issues and often passes “below the radar” of editors and reviewers. The problem of detecting the complexity of misconduct has been partially resolved by plagiarism detection software. However, interpretation of relevant reports is not always obvious or easy. This article deals with plagiarism in general and patchwork plagiarism in particular, as well as related problems that editors must deal with to maintain the integrity of scientific journals. PMID:23457762

  14. Conflict management: a primer for doctors in training

    PubMed Central

    Saltman, D C; O'Dea, N A; Kidd, M R

    2006-01-01

    Conflict in the health arena is a growing concern and is well recognised for doctors in training. Its most extreme expression, workplace violence is on the increase. There is evidence that many conflicts remain unsatisfactorily resolved or unresolved, and result in ongoing issues for staff morale. This paper describes the nature of conflict in the health care system and identifies the difference between conflict and disagreement. Using a conflict resolution model, strategies for dealing with conflict as it arises are explored and tips are provided on how to effectively manage conflict to a satisfactory resolution for all parties. PMID:16397073

  15. Genes, cells, and biobanks: Yes, there’s still a consent problem

    PubMed Central

    Murdoch, Blake

    2017-01-01

    From a research perspective, the interest in biobanking continues to intensify. Governments and industry have invested heavily in biobanks, as exemplified by initiatives like the United Kingdom Biobank and United States' Precision Medicine Initiative. But despite this enthusiasm, many profound legal and ethical challenges remain unresolved. Indeed, there continues to be disagreements about how best to obtain consent and the degree and nature of control that research participants retain over donated samples and health information. Emerging social trends—including concerns about commercialization and perceived rights of continuing control (“biorights”)—seem likely to intensify these issues. PMID:28742850

  16. Multigrid techniques for unstructured meshes

    NASA Technical Reports Server (NTRS)

    Mavriplis, D. J.

    1995-01-01

    An overview of current multigrid techniques for unstructured meshes is given. The basic principles of the multigrid approach are first outlined. Application of these principles to unstructured mesh problems is then described, illustrating various different approaches, and giving examples of practical applications. Advanced multigrid topics, such as the use of algebraic multigrid methods, and the combination of multigrid techniques with adaptive meshing strategies are dealt with in subsequent sections. These represent current areas of research, and the unresolved issues are discussed. The presentation is organized in an educational manner, for readers familiar with computational fluid dynamics, wishing to learn more about current unstructured mesh techniques.

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hattrick-Simpers, Jason R.; Gregoire, John M.; Kusne, A. Gilad

    With their ability to rapidly elucidate composition-structure-property relationships, high-throughput experimental studies have revolutionized how materials are discovered, optimized, and commercialized. It is now possible to synthesize and characterize high-throughput libraries that systematically address thousands of individual cuts of fabrication parameter space. An unresolved issue remains transforming structural characterization data into phase mappings. This difficulty is related to the complex information present in diffraction and spectroscopic data and its variation with composition and processing. Here, we review the field of automated phase diagram attribution and discuss the impact that emerging computational approaches will have in the generation of phase diagrams andmore » beyond.« less

  18. Staubli TX-90XL robot qualification at the LLIHE.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Covert, Timothy Todd

    The Light Initiated High Explosive (LIHE) Facility uses a robotic arm to spray explosive material onto test items for impulse tests. In 2007, the decision was made to replace the existing PUMA 760 robot with the Staubli TX-90XL. A qualification plan was developed and implemented to verify the safe operating conditions and failure modes of the new system. The robot satisfied the safety requirements established in the qualification plan. A performance issue described in this report remains unresolved at the time of this publication. The final readiness review concluded the qualification of this robot at the LIHE facility.

  19. Fitting Nonlinear Ordinary Differential Equation Models with Random Effects and Unknown Initial Conditions Using the Stochastic Approximation Expectation-Maximization (SAEM) Algorithm.

    PubMed

    Chow, Sy-Miin; Lu, Zhaohua; Sherwood, Andrew; Zhu, Hongtu

    2016-03-01

    The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation-maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed.

  20. The marginalisation of Indigenous students within school mathematics and the math wars: seeking resolutions within ethical spaces

    NASA Astrophysics Data System (ADS)

    Russell, Gale L.; Chernoff, Egan J.

    2013-03-01

    In mathematics education, there are (at least) two seemingly disparate and unethical issues that have been allowed to continue unresolved for decades: the math wars (traditional versus reform teaching and learning of mathematics) and the marginalisation of Indigenous students within K-12 mathematics. Willie Ermine, an Indigenous scholar, has proposed the use of ethical spaces to explore and analyse occurrences of unethical situations arising between the "intersection of Indigenous law and Canadian Legal systems" (Ermine, Indigenous Law Journal 6(1):193-203, 2007). This paper brings Ermine's notion of ethical spaces to the field of mathematics education research as the theoretical framework for analysing the aforementioned issues. The result of this analysis is a potential single theoretical resolution to both dilemmas that can also serve as a significant factor in the processes of decolonisation.

  1. FITTING NONLINEAR ORDINARY DIFFERENTIAL EQUATION MODELS WITH RANDOM EFFECTS AND UNKNOWN INITIAL CONDITIONS USING THE STOCHASTIC APPROXIMATION EXPECTATION–MAXIMIZATION (SAEM) ALGORITHM

    PubMed Central

    Chow, Sy- Miin; Lu, Zhaohua; Zhu, Hongtu; Sherwood, Andrew

    2014-01-01

    The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation–maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed. PMID:25416456

  2. Can temporal fine structure represent the fundamental frequency of unresolved harmonics?

    PubMed

    Oxenham, Andrew J; Micheyl, Christophe; Keebler, Michael V

    2009-04-01

    At least two modes of pitch perception exist: in one, the fundamental frequency (F0) of harmonic complex tones is estimated using the temporal fine structure (TFS) of individual low-order resolved harmonics; in the other, F0 is derived from the temporal envelope of high-order unresolved harmonics that interact in the auditory periphery. Pitch is typically more accurate in the former than in the latter mode. Another possibility is that pitch can sometimes be coded via the TFS from unresolved harmonics. A recent study supporting this third possibility [Moore et al. (2006a). J. Acoust. Soc. Am. 119, 480-490] based its conclusion on a condition where phase interaction effects (implying unresolved harmonics) accompanied accurate F0 discrimination (implying TFS processing). The present study tests whether these results were influenced by audible distortion products. Experiment 1 replicated the original results, obtained using a low-level background noise. However, experiments 2-4 found no evidence for the use of TFS cues with unresolved harmonics when the background noise level was raised, or the stimulus level was lowered, to render distortion inaudible. Experiment 5 measured the presence and phase dependence of audible distortion products. The results provide no evidence that TFS cues are used to code the F0 of unresolved harmonics.

  3. Regulating the chromatin landscape: structural and mechanistic perspectives.

    PubMed

    Bartholomew, Blaine

    2014-01-01

    A large family of chromatin remodelers that noncovalently modify chromatin is crucial in cell development and differentiation. They are often the targets of cancer, neurological disorders, and other human diseases. These complexes alter nucleosome positioning, higher-order chromatin structure, and nuclear organization. They also assemble chromatin, exchange out histone variants, and disassemble chromatin at defined locations. We review aspects of the structural organization of these complexes, the functional properties of their protein domains, and variation between complexes. We also address the mechanistic details of these complexes in mobilizing nucleosomes and altering chromatin structure. A better understanding of these issues will be vital for further analyses of subunits of these chromatin remodelers, which are being identified as targets in human diseases by NGS (next-generation sequencing).

  4. Unresolved trauma in mothers: intergenerational effects and the role of reorganization

    PubMed Central

    Iyengar, Udita; Kim, Sohye; Martinez, Sheila; Fonagy, Peter; Strathearn, Lane

    2014-01-01

    A mother's unresolved trauma may interfere with her ability to sensitively respond to her infant, thus affecting the development of attachment in her own child, and potentially contributing to the intergenerational transmission of trauma. One novel construct within the Dynamic Maturational Model of Attachment and Adaptation (DMM) coding of the Adult Attachment Interview (AAI) is “reorganization,” a process whereby speakers are actively changing their understanding of past and present experiences and moving toward attachment security. We conducted a study of mothers with unresolved trauma, exploring their own attachment classification, attachment outcomes of their children, and the potential effects of reorganization on child attachment. Forty-seven first-time mothers participated in the AAI during pregnancy, and returned with their child at 11 months to assess child attachment using the Strange Situation Procedure. Mothers with and without unresolved trauma were compared. We found that mothers with unresolved trauma had insecure attachment themselves and were more likely to have infants with insecure attachment. However, the one exception was that all of the mothers with unresolved trauma who were reorganizing toward secure attachment had infants with secure attachment. These preliminary findings suggest that mothers who are reorganizing may be able to more sensitively respond to their child's cues, contributing to the development of secure attachment. While our results need to be replicated in a larger cohort, this study is the first to explore the construct of reorganization and its potential relationship with child attachment. If confirmed in future studies, it may provide clinical insight into the intergenerational transmission of insecure attachment within the context of unresolved trauma. PMID:25225490

  5. Aqueous outflow - a continuum from trabecular meshwork to episcleral veins

    PubMed Central

    Carreon, Teresia; van der Merwe, Elizabeth; Fellman, Ronald L.; Johnstone, Murray; Bhattacharya, Sanjoy K.

    2016-01-01

    In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm’s canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins. PMID:28028002

  6. Synthesis and characterization of sulfolane-based amino alcohols: A combined experimental and computational study

    NASA Astrophysics Data System (ADS)

    Palchykov, Vitalii A.; Zarovnaya, Iryna S.; Tretiakov, Serhii V.; Reshetnyak, Alyona V.; Omelchenko, Iryna V.; Shishkin, Oleg V.; Okovytyy, Sergiy I.

    2018-04-01

    Aminolysis of 3,4-epoxysulfolane in aqueous media leads to a very complex mixture of products with unresolved stereochemistry. Herein, we report a detailed theoretical and experimental mechanistic investigation of this reaction along with extensive spectroscopic characterization of the resulting amino alcohols, using 1D and 2D NMR techniques (1H, 13C, NOE, NOESY, COSY, HSQC, HMBC) as well as XRD analysis. In addition to simple amines such as ammonia and benzylamine, our study also employed the more sterically hindered endo-bicyclo[2.2.1]hept-5-en-2-ylmethanamine. The mechanism of the aminolysis of 3,4-epoxysulfolane by aqueous ammonia was studied in more detail using quantum chemical calculations at the M06-2X/6-31++G** level of theory. The computational results led us to conclude that the most probable way of initial epoxide transformation is base-catalyzed rearrangement to a corresponding allylic alcohol. Subsequent formation of vicinal amino alcohols and diols proceeds via addition of ammonia or hydroxy-anions to activated double Cdbnd C bond with some preference of a cis-attack. Detailed analytical data obtained in the course of our work will be useful for the stereochemical identification of new sulfolane derivatives.

  7. Ethics, policy, and educational issues in genetic testing.

    PubMed

    Williams, Janet K; Skirton, Heather; Masny, Agnes

    2006-01-01

    Analyze ethics, public policy, and education issues that arise in the United States (US) and the United Kingdom (UK) when genomic information acquired as a result of genetic testing is introduced into healthcare services. Priorities in the Ethical, Legal, and Social Issues Research Program include privacy, integration of genetic services into clinical health care, and educational preparation of the nursing workforce. These constructs are used to examine health policies in the US and UK, and professional interactions of individuals and families with healthcare providers. Individual, family, and societal goals may conflict with current healthcare practices and policies when genetic testing is done. Current health policies do not fully address these concerns. Unresolved issues include protection of privacy of individuals while considering genetic information needs of family members, determination of appropriate monitoring of genetic tests, addressing genetic healthcare discrepancies, and assuring appropriate nursing workforce preparation. Introduction of genetic testing into health care requires that providers are knowledgeable regarding ethical, policy, and practice issues in order to minimize risk for harm, protect the rights of individuals and families, and consider societal context in the management of genetic test results. Understanding of these issues is a component of genetic nursing competency that must be addressed at all levels of nursing education.

  8. Mechanistic models versus machine learning, a fight worth fighting for the biological community?

    PubMed

    Baker, Ruth E; Peña, Jose-Maria; Jayamohan, Jayaratnam; Jérusalem, Antoine

    2018-05-01

    Ninety per cent of the world's data have been generated in the last 5 years ( Machine learning: the power and promise of computers that learn by example Report no. DES4702. Issued April 2017. Royal Society). A small fraction of these data is collected with the aim of validating specific hypotheses. These studies are led by the development of mechanistic models focused on the causality of input-output relationships. However, the vast majority is aimed at supporting statistical or correlation studies that bypass the need for causality and focus exclusively on prediction. Along these lines, there has been a vast increase in the use of machine learning models, in particular in the biomedical and clinical sciences, to try and keep pace with the rate of data generation. Recent successes now beg the question of whether mechanistic models are still relevant in this area. Said otherwise, why should we try to understand the mechanisms of disease progression when we can use machine learning tools to directly predict disease outcome? © 2018 The Author(s).

  9. The autism puzzle: challenging a mechanistic model on conceptual and historical grounds

    PubMed Central

    2013-01-01

    Although clinicians and researchers working in the field of autism are generally not concerned with philosophical categories of kinds, a model for understanding the nature of autism is important for guiding research and clinical practice. Contemporary research in the field of autism is guided by the depiction of autism as a scientific object that can be identified with systematic neuroscientific investigation. This image of autism is compatible with a permissive account of natural kinds: the mechanistic property cluster (MPC) account of natural kinds, recently proposed as the model for understanding psychiatric disorders. Despite the heterogeneity, multicausality and fuzzy boundaries that complicate autism research, a permissive account of natural kinds (MPC kinds) provides prescriptive guidance for the investigation of objective causal mechanisms that should inform nosologists in their attempt to carve autism’s boundaries at its natural joints. However, this essay will argue that a mechanistic model of autism is limited since it disregards the way in which autism relates to ideas about what kind of behavior is abnormal. As historical studies and definitions of autism show, normative issues concerning disability, impairment and societal needs have been and still are inextricably linked to how we recognize and understand autism. The current search for autism’s unity in neurobiological mechanisms ignores the values, social norms and various perspectives on mental pathology that play a significant role in 'the thing called autism’. Autism research needs to engage with these issues in order to achieve more success in the effort to become clinically valuable. PMID:24207065

  10. Error due to unresolved scales in estimation problems for atmospheric data assimilation

    NASA Astrophysics Data System (ADS)

    Janjic, Tijana

    The error arising due to unresolved scales in data assimilation procedures is examined. The problem of estimating the projection of the state of a passive scalar undergoing advection at a sequence of times is considered. The projection belongs to a finite- dimensional function space and is defined on the continuum. Using the continuum projection of the state of a passive scalar, a mathematical definition is obtained for the error arising due to the presence, in the continuum system, of scales unresolved by the discrete dynamical model. This error affects the estimation procedure through point observations that include the unresolved scales. In this work, two approximate methods for taking into account the error due to unresolved scales and the resulting correlations are developed and employed in the estimation procedure. The resulting formulas resemble the Schmidt-Kalman filter and the usual discrete Kalman filter, respectively. For this reason, the newly developed filters are called the Schmidt-Kalman filter and the traditional filter. In order to test the assimilation methods, a two- dimensional advection model with nonstationary spectrum was developed for passive scalar transport in the atmosphere. An analytical solution on the sphere was found depicting the model dynamics evolution. Using this analytical solution the model error is avoided, and the error due to unresolved scales is the only error left in the estimation problem. It is demonstrated that the traditional and the Schmidt- Kalman filter work well provided the exact covariance function of the unresolved scales is known. However, this requirement is not satisfied in practice, and the covariance function must be modeled. The Schmidt-Kalman filter cannot be computed in practice without further approximations. Therefore, the traditional filter is better suited for practical use. Also, the traditional filter does not require modeling of the full covariance function of the unresolved scales, but only modeling of the covariance matrix obtained by evaluating the covariance function at the observation points. We first assumed that this covariance matrix is stationary and that the unresolved scales are not correlated between the observation points, i.e., the matrix is diagonal, and that the values along the diagonal are constant. Tests with these assumptions were unsuccessful, indicating that a more sophisticated model of the covariance is needed for assimilation of data with nonstationary spectrum. A new method for modeling the covariance matrix based on an extended set of modeling assumptions is proposed. First, it is assumed that the covariance matrix is diagonal, that is, that the unresolved scales are not correlated between the observation points. It is postulated that the values on the diagonal depend on a wavenumber that is characteristic for the unresolved part of the spectrum. It is further postulated that this characteristic wavenumber can be diagnosed from the observations and from the estimate of the projection of the state that is being estimated. It is demonstrated that the new method successfully overcomes previously encountered difficulties.

  11. Army-NASA aircrew/aircraft integration program. Phase 5: A3I Man-Machine Integration Design and Analysis System (MIDAS) software concept document

    NASA Technical Reports Server (NTRS)

    Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Neukom, Christian; Nishimura, Sayuri; Prevost, Michael; Shankar, Renuka; Staveland, Lowell; Smith, Greg

    1992-01-01

    This is the Software Concept Document for the Man-machine Integration Design and Analysis System (MIDAS) being developed as part of Phase V of the Army-NASA Aircrew/Aircraft Integration (A3I) Progam. The approach taken in this program since its inception in 1984 is that of incremental development with clearly defined phases. Phase 1 began in 1984 and subsequent phases have progressed at approximately 10-16 month intervals. Each phase of development consists of planning, setting requirements, preliminary design, detailed design, implementation, testing, demonstration and documentation. Phase 5 began with an off-site planning meeting in November, 1990. It is expected that Phase 5 development will be complete and ready for demonstration to invited visitors from industry, government and academia in May, 1992. This document, produced during the preliminary design period of Phase 5, is intended to record the top level design concept for MIDAS as it is currently conceived. This document has two main objectives: (1) to inform interested readers of the goals of the MIDAS Phase 5 development period, and (2) to serve as the initial version of the MIDAS design document which will be continuously updated as the design evolves. Since this document is written fairly early in the design period, many design issues still remain unresolved. Some of the unresolved issues are mentioned later in this document in the sections on specific components. Readers are cautioned that this is not a final design document and that, as the design of MIDAS matures, some of the design ideas recorded in this document will change. The final design will be documented in a detailed design document published after the demonstrations.

  12. Conditions for the emergence of life on the early Earth: summary and reflections

    PubMed Central

    Jortner, Joshua

    2006-01-01

    This review attempts to situate the emergence of life on the early Earth within the scientific issues of the operational and mechanistic description of life, the conditions and constraints of prebiotic chemistry, together with bottom-up molecular fabrication and biomolecular nanofabrication and top-down miniaturization approaches to the origin of terrestrial life. PMID:17008225

  13. Towards to an Explanation for Conceptual Change: A Mechanistic Alternative

    ERIC Educational Resources Information Center

    Rusanen, Anna-Mari

    2014-01-01

    Conceptual change is one of the most studied fields in science education and psychology of learning. However, there are still some foundational issues in conceptual change research on which no clear consensus has emerged. Firstly, there is no agreement on what changes in belief and concept systems constitute conceptual change and what changes do…

  14. Paradigm Thinking: Passionate Hopefulness and More than 20 Cents of Effort

    ERIC Educational Resources Information Center

    Schultz, Robert A.

    2012-01-01

    In their introduction to the idea of a systems approach to understanding talent and giftedness, Ziegler and Phillipson broach the larger issue of the positivistic or mechanistic mindset to knowing and understanding that pervades much of what is called educational research. This worthy tactic brings to light the need to move away from the status…

  15. Spatially unresolved SED fitting can underestimate galaxy masses: a solution to the missing mass problem

    NASA Astrophysics Data System (ADS)

    Sorba, Robert; Sawicki, Marcin

    2018-05-01

    We perform spatially resolved, pixel-by-pixel Spectral Energy Distribution (SED) fitting on galaxies up to z ˜ 2.5 in the Hubble eXtreme Deep Field (XDF). Comparing stellar mass estimates from spatially resolved and spatially unresolved photometry we find that unresolved masses can be systematically underestimated by factors of up to 5. The ratio of the unresolved to resolved mass measurement depends on the galaxy's specific star formation rate (sSFR): at low sSFRs the bias is small, but above sSFR ˜ 10-9.5 yr-1 the discrepancy increases rapidly such that galaxies with sSFRs ˜ 10-8 yr-1 have unresolved mass estimates of only one-half to one-fifth of the resolved value. This result indicates that stellar masses estimated from spatially unresolved data sets need to be systematically corrected, in some cases by large amounts, and we provide an analytic prescription for applying this correction. We show that correcting stellar mass measurements for this bias changes the normalization and slope of the star-forming main sequence and reduces its intrinsic width; most dramatically, correcting for the mass bias increases the stellar mass density of the Universe at high redshift and can resolve the long-standing discrepancy between the directly measured cosmic SFR density at z ≳ 1 and that inferred from stellar mass densities (`the missing mass problem').

  16. Characterization of Sound Radiation by Unresolved Scales of Motion in Computational Aeroacoustics

    NASA Technical Reports Server (NTRS)

    Rubinstein, Robert; Zhou, Ye

    1999-01-01

    Evaluation of the sound sources in a high Reynolds number turbulent flow requires time-accurate resolution of an extremely large number of scales of motion. Direct numerical simulations will therefore remain infeasible for the forseeable future: although current large eddy simulation methods can resolve the largest scales of motion accurately the, they must leave some scales of motion unresolved. A priori studies show that acoustic power can be underestimated significantly if the contribution of these unresolved scales is simply neglected. In this paper, the problem of evaluating the sound radiation properties of the unresolved, subgrid-scale motions is approached in the spirit of the simplest subgrid stress models: the unresolved velocity field is treated as isotropic turbulence with statistical descriptors, evaluated from the resolved field. The theory of isotropic turbulence is applied to derive formulas for the total power and the power spectral density of the sound radiated by a filtered velocity field. These quantities are compared with the corresponding quantities for the unfiltered field for a range of filter widths and Reynolds numbers.

  17. The American Indian Holocaust: healing historical unresolved grief.

    PubMed

    Brave Heart, M Y; DeBruyn, L M

    1998-01-01

    American Indians experienced massive losses of lives, land, and culture from European contact and colonization resulting in a long legacy of chronic trauma and unresolved grief across generations. This phenomenon, labeled historical unresolved grief, contributes to the current social pathology of high rates of suicide, homicide, domestic violence, child abuse, alcoholism and other social problems among American Indians. The present paper describes the concept of historical unresolved grief and historical trauma among American Indians, outlining the historical as well as present social and political forces which exacerbate it. The abundant literature on Jewish Holocaust survivors and their children is used to delineate the intergenerational transmission of trauma, grief, and the survivor's child complex. Interventions based on traditional American Indian ceremonies and modern western treatment modalities for grieving and healing of those losses are described.

  18. Human Health Effects of Biphenyl: Key Findings and Scientific Issues

    PubMed Central

    Li, Zheng; Hogan, Karen A.; Cai, Christine; Rieth, Susan

    2015-01-01

    Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. Objectives: We review key findings and scientific issues regarding expected human health effects of biphenyl. Methods: Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Discussion: Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. Conclusions: The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Citation: Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703–712; http://dx.doi.org/10.1289/ehp.1509730 PMID:26529796

  19. The sigh of the oppressed: The palliative effects of ideology are stronger for people living in highly unequal neighbourhoods.

    PubMed

    Sengupta, Nikhil K; Greaves, Lara M; Osborne, Danny; Sibley, Chris G

    2017-09-01

    Ideologies that legitimize status hierarchies are associated with increased well-being. However, which ideologies have 'palliative effects', why they have these effects, and whether these effects extend to low-status groups remain unresolved issues. This study aimed to address these issues by testing the effects of the ideology of Symbolic Prejudice on well-being among low- and high-status ethnic groups (4,519 Europeans and 1,091 Māori) nested within 1,437 regions in New Zealand. Results showed that Symbolic Prejudice predicted increased well-being for both groups, but that this relationship was stronger for those living in highly unequal neighbourhoods. This suggests that it is precisely those who have the strongest need to justify inequality that accrue the most psychological benefit from subscribing to legitimizing ideologies. © 2017 The British Psychological Society.

  20. The nitrogen-vacancy colour centre in diamond

    NASA Astrophysics Data System (ADS)

    Doherty, Marcus W.; Manson, Neil B.; Delaney, Paul; Jelezko, Fedor; Wrachtrup, Jörg; Hollenberg, Lloyd C. L.

    2013-07-01

    The nitrogen-vacancy (NV) colour centre in diamond is an important physical system for emergent quantum technologies, including quantum metrology, information processing and communications, as well as for various nanotechnologies, such as biological and sub-diffraction limit imaging, and for tests of entanglement in quantum mechanics. Given this array of existing and potential applications and the almost 50 years of NV research, one would expect that the physics of the centre is well understood, however, the study of the NV centre has proved challenging, with many early assertions now believed false and many remaining issues yet to be resolved. This review represents the first time that the key empirical and ab initio results have been extracted from the extensive NV literature and assembled into one consistent picture of the current understanding of the centre. As a result, the key unresolved issues concerning the NV centre are identified and the possible avenues for their resolution are examined.

  1. Specific issues in living donor kidney transplantation: ABO - incompatibility.

    PubMed

    Thaiss, Friedrich

    2009-12-29

    Pre-emptive living kidney transplantation is the best choice of therapy to treat patients with advanced renal insufficiency. Unfortunately in up to one third of all cases kidney donation was refused due to blood group incompatibility. Limitations in donor availability for kidney transplantation therefore require that ABO-incompatible transplantation is safely established. This has changed when a new protocol was introduced in Stockholm, Sweden, in 2001. Almost 400 ABO-incompatible transplantations have since been performed in more than 20 centers with this protocol in Europe. ABO-incompatible living kidney transplantation can now be offered to our patients with advanced kidney disease as a safe procedure. To get more insight into the role ABO-incompatible organ transplantation might play in the near future transplantation centers currently involved in these processes should share their data to answer the unresolved issues we are concerned. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  2. Unresolved issues in excimer laser corneal surgery

    NASA Astrophysics Data System (ADS)

    Trokel, Stephen L.

    1991-06-01

    More than one hundred fifty clinical excimer laser units designed for corneal surgery have been developed and sold commercially. Manufacturers include Meditec Lasers in Germany, Summit Engineering, Taunton Technologies, and Visx in the United States, and Synthelabo in France. Furthermore a number of prototypes have been built in the USSR and other countries which are being investigated for their clinical use. While in the United States and Canada, substantial regulation of these devices has limited their distribution and use, sales in other parts of the world have been restricted only by market forces. Early clinical successes have created an enthusiasm for this new technology. In spite of this, substantial technical issues remain uncertain and have not been carefully studied. Indeed we have accepted certain parameters for on an almost serendipitous, empirical basis. It is a proper time to pause and consider the bases for these laser techniques.

  3. Integrating positive psychology into health-related quality of life research.

    PubMed

    Park, Crystal L

    2015-07-01

    Positive psychology is an increasingly influential force in theory and research within psychology and many related fields, including behavioral medicine, sociology, and public health. This article aims to review the ways in which positive psychology and health-related quality of life (HRQOL) research currently interface and to suggest fruitful future directions. This article reviews the basic elements of positive psychology and provides an overview of conceptual and empirical links between positive psychology and HRQOL. The role of one central aspect of positive psychology (meaning) within HRQOL is highlighted, and unresolved issues (e.g., lack of definitional clarity) are discussed. Some research on HRQOL has taken a positive psychology perspective, demonstrating the usefulness of taking a positive psychology approach. However, many areas await integration. Once conceptual and methodological issues are resolved, positive psychology may profitably inform many aspects of HRQOL research and, perhaps, clinical interventions to promote HRQOL as well.

  4. End of FY2014 Report - Filter Measurement System for Nuclear Material Storage Canisters (Including Altitude Correction for Filter Pressure Drop)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moore, Murray E.; Reeves, Kirk Patrick

    2015-02-24

    Two LANL FTS (Filter Test System ) devices for nuclear material storage canisters are fully operational. One is located in PF-4 ( i.e. the TA-55 FTS) while the other is located at the Radiation Protection Division’s Aerosol Engineering Facility ( i.e. the TA-3 FTS). The systems are functionally equivalent , with the TA-3 FTS being the test-bed for new additions and for resolving any issues found in the TA-55 FTS. There is currently one unresolved issue regarding the TA-55 FTS device. The canister lid clamp does not give a leak tight seal when testing the 1 QT (quart) or 2more » QT SAVY lids. An adapter plate is being developed that will ensure a correct test configuration when the 1 or 2 QT SAVY lid s are being tested .« less

  5. Highlights of the study of energy release in flares

    NASA Technical Reports Server (NTRS)

    Rust, D. M.; Batchelor, D. A.

    1987-01-01

    From February 26 to March 1, 1979, 32 solar flare investigators attended a workshop at Cambridge, MA to define objectives and devise a scientific program for the study of energy release in flares (SERF) during the coming solar maximum. Herein, some major results of the ensuing five-year effort to observe and understand the flare energy release process and its effects (energetic particle production, coronal and chromospheric heating, electromagnetic radiations, and mass motions and ejections) are reviewed. The central issue - what processes store and release the energy liberated in flares - remains unresolved except in the most general terms (e.g., it is generally agreed that the energy is stored in sheared or stressed magnetic fields and released by field annihilation during some MHD instability). Resolving that issue is still one of the most important goals in solar physics, but the advances during the SERF program have brought it closer.

  6. Ensemble Kalman filters for dynamical systems with unresolved turbulence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grooms, Ian, E-mail: grooms@cims.nyu.edu; Lee, Yoonsang; Majda, Andrew J.

    Ensemble Kalman filters are developed for turbulent dynamical systems where the forecast model does not resolve all the active scales of motion. Coarse-resolution models are intended to predict the large-scale part of the true dynamics, but observations invariably include contributions from both the resolved large scales and the unresolved small scales. The error due to the contribution of unresolved scales to the observations, called ‘representation’ or ‘representativeness’ error, is often included as part of the observation error, in addition to the raw measurement error, when estimating the large-scale part of the system. It is here shown how stochastic superparameterization (amore » multiscale method for subgridscale parameterization) can be used to provide estimates of the statistics of the unresolved scales. In addition, a new framework is developed wherein small-scale statistics can be used to estimate both the resolved and unresolved components of the solution. The one-dimensional test problem from dispersive wave turbulence used here is computationally tractable yet is particularly difficult for filtering because of the non-Gaussian extreme event statistics and substantial small scale turbulence: a shallow energy spectrum proportional to k{sup −5/6} (where k is the wavenumber) results in two-thirds of the climatological variance being carried by the unresolved small scales. Because the unresolved scales contain so much energy, filters that ignore the representation error fail utterly to provide meaningful estimates of the system state. Inclusion of a time-independent climatological estimate of the representation error in a standard framework leads to inaccurate estimates of the large-scale part of the signal; accurate estimates of the large scales are only achieved by using stochastic superparameterization to provide evolving, large-scale dependent predictions of the small-scale statistics. Again, because the unresolved scales contain so much energy, even an accurate estimate of the large-scale part of the system does not provide an accurate estimate of the true state. By providing simultaneous estimates of both the large- and small-scale parts of the solution, the new framework is able to provide accurate estimates of the true system state.« less

  7. Ebola epidemic of 2014-2015: unresolved ethical issues.

    PubMed

    Garbuglia, Anna Rosa

    2016-01-01

    Some ethical aspects of the management of the Ebola epidemic in Guinea, Liberia and Sierra Leone which started in January 2014, have been questionable. First, as regards the prevention of the spread of the virus, the necessary epidemiological investigations on the origin of the infection were not carried out adequately and this did not help to curb the spread of the disease. A disparity has been observed between the western and African countries' access to the treatment of patients; this infringes on the principle of equality. This paper also focuses on how the Global Public Goods for Health principle was not fully respected in the management of the epidemic.

  8. Light-Induced Capacitance Tunability in Ferroelectric Crystals.

    PubMed

    Páez-Margarit, David; Rubio-Marcos, Fernando; Ochoa, Diego A; Del Campo, Adolfo; Fernández, José F; García, José E

    2018-06-25

    The remote controlling of ferroic properties with light is nowadays a hot and highly appealing topic in materials science. Here, we shed light on some of the unresolved issues surrounding light-matter coupling in ferroelectrics. Our findings show that the capacitance and, consequently, its related intrinsic material property, i.e., the dielectric constant, can be reversibly adjusted through the light power control. High photodielectric performance is exhibited across a wide range of the visible light wavelength because of the wavelength-independence of the phenomenon. We have verified that this counterintuitive behavior can be strongly ascribed to the existence of "locally free charges" at domain wall.

  9. Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

    PubMed

    Tinsley, Grant M; Horne, Benjamin D

    2018-01-01

    Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

  10. Magnetotail Reconnection

    NASA Astrophysics Data System (ADS)

    Petrukovich, A.; Artemyev, A.; Nakamura, R.

    Reconnection is the key process responsible for the magnetotail dynamics. Driven reconnection in the distant tail is not sufficient to support global magnetospheric convection and the near Earth neutral line spontaneously forms to restore the balance. Mechanisms of initiation of such near-Earth magnetotail reconnection still represent one of major unresolved issues in space physics. We review the progress in this topic during the last decade. Recent theoretical advances suggest several variants of overcoming the famous tearing stability problem. Multipoint spacecraft observations reveal detailed structure of pre-onset current sheet of and reconnection zone down to ion larmor scale, supporting the importance of unstable state development through internal magnetotail reconfiguration.

  11. From experimental systems to evolutionary biology: an impossible journey?

    PubMed

    Morange, Michel

    2013-01-01

    The historical approach to the sciences has undergone a sea change during recent decades. Maybe the major contribution of Hans-Jörg Rheinberger to this movement was his demonstration of the importance of experimental systems, and of their transformations, in the development of the sciences. To describe these transformations, Hans-Jörg borrows metaphors from evolutionary biology. I want to argue that evolutionary biologists can find in these recent historical studies plenty of models and concepts to address unresolved issues in their discipline. At a time when transdisciplinarity is highly praised, it is useful to provide a precise description of the obstacles that have so far prevented this exchange.

  12. Methodological considerations in service use assessment for children and youth with mental health conditions; issues for economic evaluation.

    PubMed

    Woolderink, M; Lynch, F L; van Asselt, A D I; Beecham, J; Evers, S M A A; Paulus, A T G; van Schayck, C P

    2015-05-01

    Economic evaluations are increasingly used in decision-making. Accurate measurement of service use is critical to economic evaluation. This qualitative study, based on expert interviews, aims to identify best approaches to service use measurement for child mental health conditions, and to identify problems in current methods. Results suggest considerable agreement on strengths (e.g., availability of accurate instruments to measure service use) and weaknesses, (e.g., lack of unit prices for services outside the health sector) or alternative approaches to service use measurement. Experts also identified some unresolved problems, for example the lack of uniform definitions for some mental health services.

  13. Cross-validation and hypothesis testing in neuroimaging: An irenic comment on the exchange between Friston and Lindquist et al.

    PubMed

    Reiss, Philip T

    2015-08-01

    The "ten ironic rules for statistical reviewers" presented by Friston (2012) prompted a rebuttal by Lindquist et al. (2013), which was followed by a rejoinder by Friston (2013). A key issue left unresolved in this discussion is the use of cross-validation to test the significance of predictive analyses. This note discusses the role that cross-validation-based and related hypothesis tests have come to play in modern data analyses, in neuroimaging and other fields. It is shown that such tests need not be suboptimal and can fill otherwise-unmet inferential needs. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Controlling and policing substance use(rs).

    PubMed

    White, Tony

    2002-01-01

    Controlling drug use--a dynamic, global, politicalized process--is reviewed in terms of selected types of drugs, "natural levels" of drug demand and use, drug markets and the drug market environment, types of traffickers, illicit drug trade profits, approaches to drug control ("War on Drugs", "Zero Tolerance" programs and policies, "normalizing" and legalizing selected drugs), including UN's then relatively recent "Balanced Approach" and facets of drug law enforcement (drug prices and purity levels and values of drug seizures), including various rarely noted benefits to intervention programs and control agents. Unresolved issues and needed "tools" are noted while considering the implications of the first UN's World Drug Report data.

  15. Knowledge-based approach for generating target system specifications from a domain model

    NASA Technical Reports Server (NTRS)

    Gomaa, Hassan; Kerschberg, Larry; Sugumaran, Vijayan

    1992-01-01

    Several institutions in industry and academia are pursuing research efforts in domain modeling to address unresolved issues in software reuse. To demonstrate the concepts of domain modeling and software reuse, a prototype software engineering environment is being developed at George Mason University to support the creation of domain models and the generation of target system specifications. This prototype environment, which is application domain independent, consists of an integrated set of commercial off-the-shelf software tools and custom-developed software tools. This paper describes the knowledge-based tool that was developed as part of the environment to generate target system specifications from a domain model.

  16. On the linguistic status of ‘agreement’ in sign languages

    PubMed Central

    LILLO-MARTIN, DIANE; MEIER, RICHARD P.

    2013-01-01

    In signed languages, the arguments of verbs can be marked by a system of verbal modification that has been termed “agreement” (more neutrally, “directionality”). Fundamental issues regarding directionality remain unresolved and the phenomenon has characteristics that call into question its analysis as agreement. We conclude that directionality marks person in American Sign Language, and the ways person marking interacts with syntactic phenomena are largely analogous to morpho-syntactic properties of familiar agreement systems. Overall, signed languages provide a crucial test for how gestural and linguistic mechanisms can jointly contribute to the satisfaction of fundamental aspects of linguistic structure. PMID:23495262

  17. The object and the dream: Mark Rothko.

    PubMed

    Turco, Ronald

    2002-01-01

    An exploration of unconscious determinants provides useful insights in considering Mark Rothko's creativity and behavioral characteristics. A basic focus is the issue of childhood loss and unresolved grief. The studies of Martha Wolfenstein on preadolescent and childhood parent loss are paramount in considering Rothko the man. Rothko, as a result of early losses, was predisposed to recurrent depressions and bouts of anger which created difficulties in his intimate relationships. Rothko evidenced a lifelong mistrust of male authority figures which may also account for his antipathy toward psychoanalysis. His psychological life was complicated by his experiences of institutionalized anti-Semitism which further diminished his trust in others.

  18. Role of attentional tags in working memory-driven attentional capture.

    PubMed

    Kuo, Chun-Yu; Chao, Hsuan-Fu

    2014-08-01

    Recent studies have demonstrated that the contents of working memory capture attention when performing a visual search task. However, it remains an intriguing and unresolved question whether all kinds of items stored in working memory capture attention. The present study investigated this issue by manipulating the attentional tags (target or distractor) associated with information maintained in working memory. The results showed that working memory-driven attentional capture is a flexible process, and that attentional tags associated with items stored in working memory do modulate attentional capture. When items were tagged as a target, they automatically captured attention; however, when items were tagged as a distractor, attentional capture was reduced.

  19. Social Media Channels in Health Care Research and Rising Ethical Issues.

    PubMed

    Azer, Samy A

    2017-11-01

    Social media channels such as Twitter, Facebook, and LinkedIn have been used as tools in health care research, opening new horizons for research on health-related topics (e.g., the use of mobile social networking in weight loss programs). While there have been efforts to develop ethical guidelines for internet-related research, researchers still face unresolved ethical challenges. This article investigates some of the risks inherent in social media research and discusses how researchers should handle challenges related to confidentiality, privacy, and consent when social media tools are used in health-related research. © 2017 American Medical Association. All Rights Reserved.

  20. Single realization stochastic FDTD for weak scattering waves in biological random media.

    PubMed

    Tan, Tengmeng; Taflove, Allen; Backman, Vadim

    2013-02-01

    This paper introduces an iterative scheme to overcome the unresolved issues presented in S-FDTD (stochastic finite-difference time-domain) for obtaining ensemble average field values recently reported by Smith and Furse in an attempt to replace the brute force multiple-realization also known as Monte-Carlo approach with a single-realization scheme. Our formulation is particularly useful for studying light interactions with biological cells and tissues having sub-wavelength scale features. Numerical results demonstrate that such a small scale variation can be effectively modeled with a random medium problem which when simulated with the proposed S-FDTD indeed produces a very accurate result.

  1. Single realization stochastic FDTD for weak scattering waves in biological random media

    PubMed Central

    Tan, Tengmeng; Taflove, Allen; Backman, Vadim

    2015-01-01

    This paper introduces an iterative scheme to overcome the unresolved issues presented in S-FDTD (stochastic finite-difference time-domain) for obtaining ensemble average field values recently reported by Smith and Furse in an attempt to replace the brute force multiple-realization also known as Monte-Carlo approach with a single-realization scheme. Our formulation is particularly useful for studying light interactions with biological cells and tissues having sub-wavelength scale features. Numerical results demonstrate that such a small scale variation can be effectively modeled with a random medium problem which when simulated with the proposed S-FDTD indeed produces a very accurate result. PMID:27158153

  2. Attachment stability and the emergence of unresolved representations during adolescence.

    PubMed

    Aikins, Julie Wargo; Howes, Carollee; Hamilton, Claire

    2009-09-01

    This 15-year longitudinal study examined the stability of attachment representations from infancy to adolescence and investigated the emergence of unresolved representations during adolescence in a sample of 47 16-year-olds. Attachment was assessed at 12 months using the Strange Situation Procedure, at 4 years using the modified Strange Situation Procedure, and again at 16 years with the Adult Attachment Projective (AAP). The emergence of unresolved classifications in adolescence (AAP) was associated with higher rates of negative life events, low levels of early mother-child relationship security (an aggregate measure of the 12-month and 4-year measures), negative teacher-child relationship experiences in middle childhood, and low early adolescent friendship quality. The results support the growing body of evidence suggesting that changes in attachment are lawful, while adding to the growing understanding of the emergence of unresolved attachment representations.

  3. The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

    PubMed

    Piven, Oksana O; Winata, Cecilia L

    2017-12-01

    The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the mechanism by which the canonical Wnt signaling regulates development of the heart and its regeneration after damage.

  4. Intestinal irony: how probiotic bacteria outcompete bad bugs.

    PubMed

    Weiss, Guenter

    2013-07-17

    In this issue of Cell Host & Microbe, Deriu et al. present a mechanistic explanation underlying the benefits of certain probiotic bacteria. Intestinal bacteria compete for the essential nutrient iron, leading to replacement of pathogenic Salmonella by the probiotic Escherichia coli Nissle, which is better equipped with iron acquisition systems, and resolution of infectious colitis. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Survey on Security Issues in Cloud Computing and Associated Mitigation Techniques

    NASA Astrophysics Data System (ADS)

    Bhadauria, Rohit; Sanyal, Sugata

    2012-06-01

    Cloud Computing holds the potential to eliminate the requirements for setting up of high-cost computing infrastructure for IT-based solutions and services that the industry uses. It promises to provide a flexible IT architecture, accessible through internet for lightweight portable devices. This would allow multi-fold increase in the capacity or capabilities of the existing and new software. In a cloud computing environment, the entire data reside over a set of networked resources, enabling the data to be accessed through virtual machines. Since these data-centers may lie in any corner of the world beyond the reach and control of users, there are multifarious security and privacy challenges that need to be understood and taken care of. Also, one can never deny the possibility of a server breakdown that has been witnessed, rather quite often in the recent times. There are various issues that need to be dealt with respect to security and privacy in a cloud computing scenario. This extensive survey paper aims to elaborate and analyze the numerous unresolved issues threatening the cloud computing adoption and diffusion affecting the various stake-holders linked to it.

  6. State-Space Analysis of Granger-Geweke Causality Measures with Application to fMRI.

    PubMed

    Solo, Victor

    2016-05-01

    The recent interest in the dynamics of networks and the advent, across a range of applications, of measuring modalities that operate on different temporal scales have put the spotlight on some significant gaps in the theory of multivariate time series. Fundamental to the description of network dynamics is the direction of interaction between nodes, accompanied by a measure of the strength of such interactions. Granger causality and its associated frequency domain strength measures (GEMs) (due to Geweke) provide a framework for the formulation and analysis of these issues. In pursuing this setup, three significant unresolved issues emerge. First, computing GEMs involves computing submodels of vector time series models, for which reliable methods do not exist. Second, the impact of filtering on GEMs has never been definitively established. Third, the impact of downsampling on GEMs has never been established. In this work, using state-space methods, we resolve all these issues and illustrate the results with some simulations. Our analysis is motivated by some problems in (fMRI) brain imaging, to which we apply it, but it is of general applicability.

  7. State-Space Analysis of Granger-Geweke Causality Measures with Application to fMRI

    PubMed Central

    Solo, Victor

    2017-01-01

    The recent interest in the dynamics of networks and the advent, across a range of applications, of measuring modalities that operate on different temporal scales have put the spotlight on some significant gaps in the theory of multivariate time series. Fundamental to the description of network dynamics is the direction of interaction between nodes, accompanied by a measure of the strength of such interactions. Granger causality and its associated frequency domain strength measures (GEMs) (due to Geweke) provide a framework for the formulation and analysis of these issues. In pursuing this setup, three significant unresolved issues emerge. First, computing GEMs involves computing submodels of vector time series models, for which reliable methods do not exist. Second, the impact of filtering on GEMs has never been definitively established. Third, the impact of downsampling on GEMs has never been established. In this work, using state-space methods, we resolve all these issues and illustrate the results with some simulations. Our analysis is motivated by some problems in (fMRI) brain imaging, to which we apply it, but it is of general applicability. PMID:26942749

  8. Biomechanics meets the ecological niche: the importance of temporal data resolution.

    PubMed

    Kearney, Michael R; Matzelle, Allison; Helmuth, Brian

    2012-03-15

    The emerging field of mechanistic niche modelling aims to link the functional traits of organisms to their environments to predict survival, reproduction, distribution and abundance. This approach has great potential to increase our understanding of the impacts of environmental change on individuals, populations and communities by providing functional connections between physiological and ecological response to increasingly available spatial environmental data. By their nature, such mechanistic models are more data intensive in comparison with the more widely applied correlative approaches but can potentially provide more spatially and temporally explicit predictions, which are often needed by decision makers. A poorly explored issue in this context is the appropriate level of temporal resolution of input data required for these models, and specifically the error in predictions that can be incurred through the use of temporally averaged data. Here, we review how biomechanical principles from heat-transfer and metabolic theory are currently being used as foundations for mechanistic niche models and consider the consequences of different temporal resolutions of environmental data for modelling the niche of a behaviourally thermoregulating terrestrial lizard. We show that fine-scale temporal resolution (daily) data can be crucial for unbiased inference of climatic impacts on survival, growth and reproduction. This is especially so for species with little capacity for behavioural buffering, because of behavioural or habitat constraints, and for detecting temporal trends. However, coarser-resolution data (long-term monthly averages) can be appropriate for mechanistic studies of climatic constraints on distribution and abundance limits in thermoregulating species at broad spatial scales.

  9. Evidence for Unresolved Exoplanet-hosting Binaries in Gaia DR2

    NASA Astrophysics Data System (ADS)

    Evans, Daniel F.

    2018-05-01

    This note describes an effort to detect additional stellar sources in known transiting exoplanet (TEP) systems, which are unresolved or barely resolved in the Gaia Data Release 2 (DR2) catalogue. The presence of multiple unresolved stars in photometric and spectroscopic observations of a transiting planetary system biases measurements of the planet's radius, mass, and atmospheric conditions. In addition to the effect on individual planetary systems, the presence of unresolved stars across the sample of known exoplanets biases our overall understanding of planetary systems, due to the systematic underestimation of both masses and radii. This work uses the Astrometric Goodness of Fit in the Along-Scan direction (GOF_AL) and the Astrometric Excess Noise as indicators of poorly-resolved binaries. Many known close binaries in the exoplanet host star sample have highly significant GOF_AL and Astrometric Excess Noise values, such as WASP-20AB with Astrometric Excess Noise significant at $4720\\sigma$ and GOF_AL=124.

  10. In-air and pressurized water reactor environment fatigue experiments of 316 stainless steel to study the effect of environment on cyclic hardening

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mohanty, Subhasish; Soppet, William K.; Majumdar, Saurindranath

    Argonne National Laboratory (ANL), under the sponsorship of Department of Energy’s Light Water Reactor Sustainability (LWRS) program, is trying to develop a mechanistic approach for more accurate life estimation of LWR components. In this context, ANL has conducted many fatigue experiments under different test and environment conditions on type 316 stainless steel (316SS) material which is widely used in the US reactors. Contrary to the conventional S~N curve based empirical fatigue life estimation approach, the aim of the present DOE sponsored work is to develop an understanding of the material ageing issues more mechanistically (e.g. time dependent hardening and softening)more » under different test and environmental conditions. Better mechanistic understanding will help develop computer-based advanced modeling tools to better extrapolate stress-strain evolution of reactor components under multi-axial stress states and hence help predict their fatigue life more accurately. In this paper (part-I) the fatigue experiments under different test and environment conditions and related stress-strain results for 316 SS are discussed. In a second paper (part-II) the related evolutionary cyclic plasticity material modeling techniques and results are discussed.« less

  11. Comparison of mechanistic transport cycle models of ABC exporters.

    PubMed

    Szöllősi, Dániel; Rose-Sperling, Dania; Hellmich, Ute A; Stockner, Thomas

    2018-04-01

    ABC (ATP binding cassette) transporters, ubiquitous in all kingdoms of life, carry out essential substrate transport reactions across cell membranes. Their transmembrane domains bind and translocate substrates and are connected to a pair of nucleotide binding domains, which bind and hydrolyze ATP to energize import or export of substrates. Over four decades of investigations into ABC transporters have revealed numerous details from atomic-level structural insights to their functional and physiological roles. Despite all these advances, a comprehensive understanding of the mechanistic principles of ABC transporter function remains elusive. The human multidrug resistance transporter ABCB1, also referred to as P-glycoprotein (P-gp), is one of the most intensively studied ABC exporters. Using ABCB1 as the reference point, we aim to compare the dominating mechanistic models of substrate transport and ATP hydrolysis for ABC exporters and to highlight the experimental and computational evidence in their support. In particular, we point out in silico studies that enhance and complement available biochemical data. "This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain." Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Fast charging technique for high power LiFePO4 batteries: A mechanistic analysis of aging

    NASA Astrophysics Data System (ADS)

    Anseán, D.; Dubarry, M.; Devie, A.; Liaw, B. Y.; García, V. M.; Viera, J. C.; González, M.

    2016-07-01

    One of the major issues hampering the acceptance of electric vehicles (EVs) is the anxiety associated with long charging time. Hence, the ability to fast charging lithium-ion battery (LIB) systems is gaining notable interest. However, fast charging is not tolerated by all LIB chemistries because it affects battery functionality and accelerates its aging processes. Here, we investigate the long-term effects of multistage fast charging on a commercial high power LiFePO4-based cell and compare it to another cell tested under standard charging. Coupling incremental capacity (IC) and IC peak area analysis together with mechanistic model simulations ('Alawa' toolbox with harvested half-cell data), we quantify the degradation modes that cause aging of the tested cells. The results show that the proposed fast charging technique caused similar aging effects as standard charging. The degradation is caused by a linear loss of lithium inventory, coupled with a less degree of linear loss of active material on the negative electrode. This study validates fast charging as a feasible mean of operation for this particular LIB chemistry and cell architecture. It also illustrates the benefits of a mechanistic approach to understand cell degradation on commercial cells.

  13. 28 CFR 42.610 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Agency enforcement of unresolved complaints. 42.610 Section 42.610 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Procedures for Complaints of Employment Discrimination Filed...

  14. The Nature of the Unresolved Extragalactic Cosmic Soft X-Ray Background

    NASA Technical Reports Server (NTRS)

    Cappelluti, N.; Ranalli, P.; Roncarelli, M.; Arevalo, P.; Zamorani, G.; Comastri, A.; Gilli, R.; Rovilos, E.; Vignali, C.; Allevato, V.; hide

    2013-01-01

    In this paper we investigate the power spectrum of the unresolved 0.5-2 keV cosmic X-ray background (CXB) with deep Chandra 4-Msec (Ms) observations in the Chandra Deep Field South (CDFS). We measured a signal that, on scales >30 arcsec, is significantly higher than the shot noise and is increasing with angular scale. We interpreted this signal as the joint contribution of clustered undetected sources like active galactic nuclei (AGN), galaxies and the intergalactic medium (IGM). The power of unresolved cosmic source fluctuations accounts for approximately 12 per cent of the 0.5-2 keV extragalactic CXB. Overall, our modelling predicts that approximately 20 per cent of the unresolved CXB flux is produced by low-luminosity AGN, approximately 25 per cent by galaxies and approximately 55 per cent by the IGM. We do not find any direct evidence of the so-called 'warm hot intergalactic medium' (i.e. matter with 10(exp 5) less than T less than 10(exp 7) K and density contrast delta less than 1000), but we estimated that it could produce about 1/7 of the unresolved CXB. We placed an upper limit on the space density of postulated X-ray-emitting early black holes at z greater than 7.5 and compared it with supermassive black hole evolution models.

  15. Kinetically-Defined Component Actions in Gene Repression

    PubMed Central

    Chow, Carson C.; Finn, Kelsey K.; Storchan, Geoffery B.; Lu, Xinping; Sheng, Xiaoyan; Simons, S. Stoney

    2015-01-01

    Gene repression by transcription factors, and glucocorticoid receptors (GR) in particular, is a critical, but poorly understood, physiological response. Among the many unresolved questions is the difference between GR regulated induction and repression, and whether transcription cofactor action is the same in both. Because activity classifications based on changes in gene product level are mechanistically uninformative, we present a theory for gene repression in which the mechanisms of factor action are defined kinetically and are consistent for both gene repression and induction. The theory is generally applicable and amenable to predictions if the dose-response curve for gene repression is non-cooperative with a unit Hill coefficient, which is observed for GR-regulated repression of AP1LUC reporter induction by phorbol myristate acetate. The theory predicts the mechanism of GR and cofactors, and where they act with respect to each other, based on how each cofactor alters the plots of various kinetic parameters vs. cofactor. We show that the kinetically-defined mechanism of action of each of four factors (reporter gene, p160 coactivator TIF2, and two pharmaceuticals [NU6027 and phenanthroline]) is the same in GR-regulated repression and induction. What differs is the position of GR action. This insight should simplify clinical efforts to differentially modulate factor actions in gene induction vs. gene repression. PMID:25816223

  16. Statistical Methods for Identifying Sequence Motifs Affecting Point Mutations

    PubMed Central

    Zhu, Yicheng; Neeman, Teresa; Yap, Von Bing; Huttley, Gavin A.

    2017-01-01

    Mutation processes differ between types of point mutation, genomic locations, cells, and biological species. For some point mutations, specific neighboring bases are known to be mechanistically influential. Beyond these cases, numerous questions remain unresolved, including: what are the sequence motifs that affect point mutations? How large are the motifs? Are they strand symmetric? And, do they vary between samples? We present new log-linear models that allow explicit examination of these questions, along with sequence logo style visualization to enable identifying specific motifs. We demonstrate the performance of these methods by analyzing mutation processes in human germline and malignant melanoma. We recapitulate the known CpG effect, and identify novel motifs, including a highly significant motif associated with A→G mutations. We show that major effects of neighbors on germline mutation lie within ±2 of the mutating base. Models are also presented for contrasting the entire mutation spectra (the distribution of the different point mutations). We show the spectra vary significantly between autosomes and X-chromosome, with a difference in T→C transition dominating. Analyses of malignant melanoma confirmed reported characteristic features of this cancer, including statistically significant strand asymmetry, and markedly different neighboring influences. The methods we present are made freely available as a Python library https://bitbucket.org/pycogent3/mutationmotif. PMID:27974498

  17. Quantitative measurement of stream respiration using the resazurin-resorufin system

    NASA Astrophysics Data System (ADS)

    Gonzalez Pinzon, R. A.; Acker, S.; Haggerty, R.; Myrold, D.

    2011-12-01

    After three decades of active research in hydrology and stream ecology, the relationship between stream solute transport, metabolism and nutrient dynamics is still unresolved. These knowledge gaps obscure the function of stream ecosystems and how they interact with other landscape processes. To date, measuring rates of stream metabolism is accomplished with techniques that have vast uncertainties and are not spatially representative. These limitations mask the role of metabolism in nutrient processing. Clearly, more robust techniques are needed to develop mechanistic relationships that will ultimately improve our fundamental understanding of in-stream processes and how streams interact with other ecosystems. We investigated the "metabolic window of detection" of the Resazurin (Raz)-Resorufin (Rru) system (Haggerty et al., 2008, 2009). Although previous results have shown that the transformation of Raz to Rru is strongly correlated with respiration, a quantitative relationship between them is needed. We investigated this relationship using batch experiments with pure cultures (aerobic and anaerobic) and flow-through columns with incubated sediments from four different streams. The results suggest that the Raz-Rru system is a suitable approach that will enable hydrologists and stream ecologists to measure in situ and in vivo respiration at different scales, thus opening a reliable alternative to investigate how solute transport and stream metabolism control nutrient processing.

  18. Large-scale outflows in luminous QSOs revisited. The impact of beam smearing on AGN feedback efficiencies

    NASA Astrophysics Data System (ADS)

    Husemann, B.; Scharwächter, J.; Bennert, V. N.; Mainieri, V.; Woo, J.-H.; Kakkad, D.

    2016-10-01

    Context. Feedback from active galactic nuclei (AGN) is thought to play an important role in quenching star formation in galaxies. However, the efficiency with which AGN dissipate their radiative energy into the ambient medium remains strongly debated. Aims: Enormous observational efforts have been made to constrain the energetics of AGN feedback by mapping the kinematics of the ionized gas on kpc scale. We study how the observed kinematics and inferred energetics are affected by beam smearing of a bright unresolved narrow-line region (NLR) due to seeing. Methods: We re-analyse optical integral-field spectroscopy of a sample of twelve luminous unobscured quasi-stellar objects (QSOs) (0.4

  19. Quasi parton distributions and the gradient flow

    DOE PAGES

    Monahan, Christopher; Orginos, Kostas

    2017-03-22

    We propose a new approach to determining quasi parton distribution functions (PDFs) from lattice quantum chromodynamics. By incorporating the gradient flow, this method guarantees that the lattice quasi PDFs are finite in the continuum limit and evades the thorny, and as yet unresolved, issue of the renormalization of quasi PDFs on the lattice. In the limit that the flow time is much smaller than the length scale set by the nucleon momentum, the moments of the smeared quasi PDF are proportional to those of the lightfront PDF. Finally, we use this relation to derive evolution equations for the matching kernelmore » that relates the smeared quasi PDF and the light-front PDF.« less

  20. Quasi parton distributions and the gradient flow

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monahan, Christopher; Orginos, Kostas

    We propose a new approach to determining quasi parton distribution functions (PDFs) from lattice quantum chromodynamics. By incorporating the gradient flow, this method guarantees that the lattice quasi PDFs are finite in the continuum limit and evades the thorny, and as yet unresolved, issue of the renormalization of quasi PDFs on the lattice. In the limit that the flow time is much smaller than the length scale set by the nucleon momentum, the moments of the smeared quasi PDF are proportional to those of the lightfront PDF. Finally, we use this relation to derive evolution equations for the matching kernelmore » that relates the smeared quasi PDF and the light-front PDF.« less

  1. For Richer, for Poorer: Money as a Topic of Marital Conflict in the Home

    PubMed Central

    Papp, Lauren M.; Cummings, E. Mark; Goeke-Morey, Marcie C.

    2011-01-01

    Guided by a family stress perspective, we examined the hypothesis that discussing money would be associated with the handling of marital conflict in the home. Analyses were based on dyadic hierarchical linear modeling of 100 husbands’ and 100 wives’ diary reports of 748 conflict instances. Contrary to findings from previous laboratory-based surveys, spouses did not rate money as the most frequent source of marital conflict in the home. However, compared to non-money issues, marital conflicts about money were more pervasive, problematic, and recurrent, and remained unresolved, despite including more attempts at problem solving. Implications for professionals who assist couples in managing their relationships and family finances are discussed. PMID:22162622

  2. Tornadogenesis via squall line and supercell interaction revisited - The 15 November 1989 Huntsville tornado

    NASA Technical Reports Server (NTRS)

    Goodman, Steven J.; Knupp, Kevin R.

    1990-01-01

    A case study analyzing the environmental setting and storm system morphology that provides observational evidence of a mechanism involving the interaction of a gust front with a preexisting mesocyclone is presented. This case serves to reemphasize the existence of a high conditional probability of tornado occurrence, given the merger of a gust front (or storm outflow) with a moderate to strong thunderstorm ahead of it. The resultant data serve to illustrate some important unresolved issues relevant to the severe weather warning system that involve the present and planned local warning and network radars, and future algorithms that might intelligently integrate other data sources and models with the radar data.

  3. Tungsten dust remobilization under steady-state and transient plasma conditions

    DOE PAGES

    Ratynskaia, S.; Tolias, P.; De Angeli, M.; ...

    2016-11-22

    Remobilization is one of the most prominent unresolved fusion dust-relevant issues, strongly related to the lifetime of dust in plasma-wetted regions, the survivability of dust on hot plasma-facing surfaces and the formation of dust accumulation sites. A systematic cross-machine study has been initiated to investigate the remobilization of tungsten micron-size dust from tungsten surfaces implementing a newly developed technique based on controlled pre-adhesion by gas dynamics methods. It has been utilized in a number of devices and has provided new insights on remobilization under steady-state and transient conditions. In conclusion, the experiments are interpreted with contact mechanics theory and heatmore » conduction models.« less

  4. History of cardiopulmonary bypass (CPB).

    PubMed

    Hessel, Eugene A

    2015-06-01

    The development of cardiopulmonary bypass (CPB), thereby permitting open-heart surgery, is one of the most important advances in medicine in the 20th century. Many currently practicing cardiac anesthesiologists, cardiac surgeons, and perfusionists are unaware of how recently it came into use (60 years) and how much the practice of CPB has changed during its short existence. In this paper, the development of CPB and the many changes and progress that has taken place over this brief period of time, making it a remarkably safe endeavor, are reviewed. The many as yet unresolved questions are also identified, which sets the stage for the other papers in this issue of this journal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Thermal, dynamic and compositional aspects of the core-forming Earth

    NASA Technical Reports Server (NTRS)

    Stevenson, D. J.

    1985-01-01

    Core formation is the most important and singular differentiation event in the history of a terrestrial planet. It almost certainly involved the downward migration of a partially or wholly molten iron alloy through a silicate and oxide mantle, and was contemporaneous with accretion. Several important, unresolved issues which have implications for mantle and core geochemistry, the thermal history of the Earth, and the origin of geomagnetism are addressed: whether the early Earth was molten; whether core formation involved low or high pressure geochemistry, or both; early Earth mantle homogenization; whether equilibration established between core forming material and the mantle through which it migrated; and how much iron is stranded and unable to reach the core.

  6. Perspective: Composition–structure–property mapping in high-throughput experiments: Turning data into knowledge

    DOE PAGES

    Hattrick-Simpers, Jason R.; Gregoire, John M.; Kusne, A. Gilad

    2016-05-26

    With their ability to rapidly elucidate composition-structure-property relationships, high-throughput experimental studies have revolutionized how materials are discovered, optimized, and commercialized. It is now possible to synthesize and characterize high-throughput libraries that systematically address thousands of individual cuts of fabrication parameter space. An unresolved issue remains transforming structural characterization data into phase mappings. This difficulty is related to the complex information present in diffraction and spectroscopic data and its variation with composition and processing. Here, we review the field of automated phase diagram attribution and discuss the impact that emerging computational approaches will have in the generation of phase diagrams andmore » beyond.« less

  7. For Richer, for Poorer: Money as a Topic of Marital Conflict in the Home.

    PubMed

    Papp, Lauren M; Cummings, E Mark; Goeke-Morey, Marcie C

    2009-02-01

    Guided by a family stress perspective, we examined the hypothesis that discussing money would be associated with the handling of marital conflict in the home. Analyses were based on dyadic hierarchical linear modeling of 100 husbands' and 100 wives' diary reports of 748 conflict instances. Contrary to findings from previous laboratory-based surveys, spouses did not rate money as the most frequent source of marital conflict in the home. However, compared to non-money issues, marital conflicts about money were more pervasive, problematic, and recurrent, and remained unresolved, despite including more attempts at problem solving. Implications for professionals who assist couples in managing their relationships and family finances are discussed.

  8. Multijunction cells for concentrators: Technology prospects

    NASA Technical Reports Server (NTRS)

    Ferber, R. R. (Compiler); Costogue, E. N. (Compiler); Shimada, K. (Compiler)

    1984-01-01

    Development of high-efficiency multijunction solar cells for concentrator applications is a key step in achieving the goals of the U.S. Department of Energy National Photovoltaics Program. This report summarizes findings of an issue study conducted by the Jet Propulsion Laboratory Photovoltaic Analysis and Integration Center, with the assistance of the Solar Energy Research Institute and Sandia National laboratoies, which surveyed multijunction cell research for concentrators undertaken by federal agencies and by private industry. The team evaluated the potentials of research activities sponsored by DOE and by corporate funding to achieve projected high-efficiency goals and developed summary statements regarding industry expectations. Recommendations are made for the direction of future work to address specific unresolved aspects of multijunction cell technology.

  9. USMC Ground Surveillance Robot (GSR): Lessons Learned

    NASA Astrophysics Data System (ADS)

    Harmon, S. Y.

    1987-02-01

    This paper describes the design of an autonomous vehicle and the lessons learned during the implementation of that complex robot. The major problems encountered to which solutions were found include sensor processing bandwidth limitations, coordination of the interactions between major subsystems, sensor data fusion and system knowledge representation. Those problems remaining unresolved include system complexity management, the lack of powerful system monitoring and debugging tools, exploratory implementation of a complex system and safety and testing issues. Many of these problems arose from working with underdeveloped and continuously evolving technology and will probably be resolved as the technological resources mature and stabilize. Unfortunately, other problems will continue to plague developers throughout the evolution of autonomous system technology.

  10. Pediatric surgeons and anesthesiologists expand the dialogue on the neurotoxicity question, rationale for early and delayed surgeries, and practice changes while awaiting definitive evidence.

    PubMed

    Byrne, Mary W; Casale, Pasquale; Garzon, Maria; Hyman, Joshua E; Lin, Albert Y; Lynch, Lisa R; Schleien, Charles L; Stylianos, Steven

    2014-10-01

    The Pediatric Anesthesia NeuroDevelopment Assessment team at Columbia University Medical Center Department of Anesthesiology convened its fourth biennial Symposium to address unresolved issues concerning potential neurotoxic effects of anesthetic agents and sedatives on young children and to assess study findings to date. Dialogue initiated at the third Symposium was continued between anesthesiologists, researchers, and a panel of expert pediatric surgeons representing general surgery and dermatology, orthopedic, and urology specialties. The panel explored the need to balance benefits of early surgery using improved technologies against potential anesthetic risks, practice changes while awaiting definitive answers, and importance of continued interprofessional dialogue.

  11. The Oxford Questions on the foundations of quantum physics

    PubMed Central

    Briggs, G. A. D.; Butterfield, J. N.; Zeilinger, A.

    2013-01-01

    The twentieth century saw two fundamental revolutions in physics—relativity and quantum. Daily use of these theories can numb the sense of wonder at their immense empirical success. Does their instrumental effectiveness stand on the rock of secure concepts or the sand of unresolved fundamentals? Does measuring a quantum system probe, or even create, reality or merely change belief? Must relativity and quantum theory just coexist or might we find a new theory which unifies the two? To bring such questions into sharper focus, we convened a conference on Quantum Physics and the Nature of Reality. Some issues remain as controversial as ever, but some are being nudged by theory's secret weapon of experiment. PMID:24062626

  12. Wind shear detection. Forward-looking sensor technology

    NASA Technical Reports Server (NTRS)

    Bracalente, E. M. (Compiler); Delnore, V. E. (Compiler)

    1987-01-01

    A meeting took place at NASA Langley Research Center in February 1987 to discuss the development and eventual use of forward-looking remote sensors for the detection and avoidance of wind shear by aircraft. The participants represented industry, academia, and government. The meeting was structured to provide first a review of the current FAA and NASA wind shear programs, then to define what really happens to the airplane, and finally to give technology updates on the various types of forward-looking sensors. This document is intended to informally record the essence of the technology updates (represented here through unedited duplication of the vugraphs used), and the floor discussion following each presentation. Also given are key issues remaining unresolved.

  13. The Oxford Questions on the foundations of quantum physics.

    PubMed

    Briggs, G A D; Butterfield, J N; Zeilinger, A

    2013-09-08

    The twentieth century saw two fundamental revolutions in physics-relativity and quantum. Daily use of these theories can numb the sense of wonder at their immense empirical success. Does their instrumental effectiveness stand on the rock of secure concepts or the sand of unresolved fundamentals? Does measuring a quantum system probe, or even create, reality or merely change belief? Must relativity and quantum theory just coexist or might we find a new theory which unifies the two? To bring such questions into sharper focus, we convened a conference on Quantum Physics and the Nature of Reality. Some issues remain as controversial as ever, but some are being nudged by theory's secret weapon of experiment.

  14. Simulation of the human-telerobot interface on the Space Station

    NASA Technical Reports Server (NTRS)

    Stuart, Mark A.; Smith, Randy L.

    1993-01-01

    Many issues remain unresolved concerning the components of the human-telerobot interface presented in this work. It is critical that these components be optimally designed and arranged to ensure, not only that the overall system's goals are met, but but that the intended end-user has been optimally accommodated. With sufficient testing and evaluation throughout the development cycle, the selection of the components to use in the final telerobotic system can promote efficient, error-free performance. It is recommended that whole-system simulation with full-scale mockups be used to help design the human-telerobot interface. It is contended that the use of simulation can facilitate this design and evaluation process.

  15. Detecting unresolved binary stars in Euclid VIS images

    NASA Astrophysics Data System (ADS)

    Kuntzer, T.; Courbin, F.

    2017-10-01

    Measuring a weak gravitational lensing signal to the level required by the next generation of space-based surveys demands exquisite reconstruction of the point-spread function (PSF). However, unresolved binary stars can significantly distort the PSF shape. In an effort to mitigate this bias, we aim at detecting unresolved binaries in realistic Euclid stellar populations. We tested methods in numerical experiments where (I) the PSF shape is known to Euclid requirements across the field of view; and (II) the PSF shape is unknown. We drew simulated catalogues of PSF shapes for this proof-of-concept paper. Following the Euclid survey plan, the objects were observed four times. We propose three methods to detect unresolved binary stars. The detection is based on the systematic and correlated biases between exposures of the same object. One method is a simple correlation analysis, while the two others use supervised machine-learning algorithms (random forest and artificial neural network). In both experiments, we demonstrate the ability of our methods to detect unresolved binary stars in simulated catalogues. The performance depends on the level of prior knowledge of the PSF shape and the shape measurement errors. Good detection performances are observed in both experiments. Full complexity, in terms of the images and the survey design, is not included, but key aspects of a more mature pipeline are discussed. Finding unresolved binaries in objects used for PSF reconstruction increases the quality of the PSF determination at arbitrary positions. We show, using different approaches, that we are able to detect at least binary stars that are most damaging for the PSF reconstruction process. The code corresponding to the algorithms used in this work and all scripts to reproduce the results are publicly available from a GitHub repository accessible via http://lastro.epfl.ch/software

  16. Modelling turbulent boundary layer flow over fractal-like multiscale terrain using large-eddy simulations and analytical tools.

    PubMed

    Yang, X I A; Meneveau, C

    2017-04-13

    In recent years, there has been growing interest in large-eddy simulation (LES) modelling of atmospheric boundary layers interacting with arrays of wind turbines on complex terrain. However, such terrain typically contains geometric features and roughness elements reaching down to small scales that typically cannot be resolved numerically. Thus subgrid-scale models for the unresolved features of the bottom roughness are needed for LES. Such knowledge is also required to model the effects of the ground surface 'underneath' a wind farm. Here we adapt a dynamic approach to determine subgrid-scale roughness parametrizations and apply it for the case of rough surfaces composed of cuboidal elements with broad size distributions, containing many scales. We first investigate the flow response to ground roughness of a few scales. LES with the dynamic roughness model which accounts for the drag of unresolved roughness is shown to provide resolution-independent results for the mean velocity distribution. Moreover, we develop an analytical roughness model that accounts for the sheltering effects of large-scale on small-scale roughness elements. Taking into account the shading effect, constraints from fundamental conservation laws, and assumptions of geometric self-similarity, the analytical roughness model is shown to provide analytical predictions that agree well with roughness parameters determined from LES.This article is part of the themed issue 'Wind energy in complex terrains'. © 2017 The Author(s).

  17. Searching for Unresolved Binary Brown Dwarfs

    NASA Astrophysics Data System (ADS)

    Albretsen, Jacob; Stephens, Denise

    2007-10-01

    There are currently L and T brown dwarfs (BDs) with errors in their classification of +/- 1 to 2 spectra types. Metallicity and gravitational differences have accounted for some of these discrepancies, and recent studies have shown unresolved binary BDs may offer some explanation as well. However limitations in technology and resources often make it difficult to clearly resolve an object that may be binary in nature. Stephens and Noll (2006) identified statistically strong binary source candidates from Hubble Space Telescope (HST) images of Trans-Neptunian Objects (TNOs) that were apparently unresolved using model point-spread functions for single and binary sources. The HST archive contains numerous observations of BDs using the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) that have never been rigorously analyzed for binary properties. Using methods developed by Stephens and Noll (2006), BD observations from the HST data archive are being analyzed for possible unresolved binaries. Preliminary results will be presented. This technique will identify potential candidates for future observations to determine orbital information.

  18. A call for theory to support the use of causal-formative indicators: A commentary on Bollen and Diamantopoulos (2017).

    PubMed

    Hardin, Andrew

    2017-09-01

    In this issue, Bollen and Diamantopoulos (2017) defend causal-formative indicators against several common criticisms leveled by scholars who oppose their use. In doing so, the authors make several convincing assertions: Constructs exist independently from their measures; theory determines whether indicators cause or measure latent variables; and reflective and causal-formative indicators are both subject to interpretational confounding. However, despite being a well-reasoned, comprehensive defense of causal-formative indicators, no single article can address all of the issues associated with this debate. Thus, Bollen and Diamantopoulos leave a few fundamental issues unresolved. For example, how can researchers establish the reliability of indicators that may include measurement error? Moreover, how should researchers interpret disturbance terms that capture sources of influence related to both the empirical definition of the latent variable and to the theoretical definition of the construct? Relatedly, how should researchers reconcile the requirement for a census of causal-formative indicators with the knowledge that indicators are likely missing from the empirically estimated latent variable? This commentary develops 6 related research questions to draw attention to these fundamental issues, and to call for future research that can lead to the development of theory to guide the use of causal-formative indicators. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Care at End of Life Influences Grief: A Nationwide Long-Term Follow-Up among Young Adults Who Lost a Brother or Sister to Childhood Cancer.

    PubMed

    Lövgren, Malin; Sveen, Josefin; Nyberg, Tommy; Eilegård Wallin, Alexandra; Prigerson, Holly G; Steineck, Gunnar; Kreicbergs, Ulrika

    2018-02-01

    A majority of cancer-bereaved siblings report long-term unresolved grief, thus it is important to identify factors that may contribute to resolving their grief. To identify modifiable or avoidable family and care-related factors associated with unresolved grief among siblings two to nine years post loss. This is a nationwide Swedish postal survey. Study-specific questions and the standardized instrument Hospital Anxiety and Depression Scale. Primary outcome was unresolved grief, and family and care-related factors were used as predictors. Cancer-bereaved sibling (N = 174) who lost a brother/sister to childhood cancer during 2000-2007 in Sweden (participation rate 73%). Seventy-three were males and 101 females. The age of the siblings at time of loss was 12-25 years and at the time of the survey between 19 and 33 years. Several predictors for unresolved grief were identified: siblings' perception that it was not a peaceful death [odds ratio (OR): 9.86, 95% confidence interval (CI): 2.39-40.65], limited information given to siblings the last month of life (OR: 5.96, 95% CI: 1.87-13.68), information about the impending death communicated the day before it occurred (OR: 2.73, 95% CI: 1.02-7.33), siblings' avoidance of the doctors (OR: 3.22, 95% CI: 0.75-13.76), and lack of communication with family (OR: 2.86, 95% CI: 1.01-8.04) and people outside the family about death (OR: 5.07, 95% CI: 1.64-15.70). Depressive symptoms (OR: 1.27, 95% CI: 1.12-1.45) and time since loss (two to four years: OR: 10.36, 95% CI: 2.87-37.48 and five to seven years: OR: 8.36, 95% CI: 2.36-29.57) also predicted unresolved grief. Together, these predictors explained 54% of the variance of unresolved grief. Siblings' perception that it was not a peaceful death and poor communication with family, friends, and healthcare increased the risk for unresolved grief among the siblings.

  20. Mechanistic Explanations for Restricted Evolutionary Paths That Emerge from Gene Regulatory Networks

    PubMed Central

    Cotterell, James; Sharpe, James

    2013-01-01

    The extent and the nature of the constraints to evolutionary trajectories are central issues in biology. Constraints can be the result of systems dynamics causing a non-linear mapping between genotype and phenotype. How prevalent are these developmental constraints and what is their mechanistic basis? Although this has been extensively explored at the level of epistatic interactions between nucleotides within a gene, or amino acids within a protein, selection acts at the level of the whole organism, and therefore epistasis between disparate genes in the genome is expected due to their functional interactions within gene regulatory networks (GRNs) which are responsible for many aspects of organismal phenotype. Here we explore epistasis within GRNs capable of performing a common developmental function – converting a continuous morphogen input into discrete spatial domains. By exploring the full complement of GRN wiring designs that are able to perform this function, we analyzed all possible mutational routes between functional GRNs. Through this study we demonstrate that mechanistic constraints are common for GRNs that perform even a simple function. We demonstrate a common mechanistic cause for such a constraint involving complementation between counter-balanced gene-gene interactions. Furthermore we show how such constraints can be bypassed by means of “permissive” mutations that buffer changes in a direct route between two GRN topologies that would normally be unviable. We show that such bypasses are common and thus we suggest that unlike what was observed in protein sequence-function relationships, the “tape of life” is less reproducible when one considers higher levels of biological organization. PMID:23613807

  1. EU Framework 6 Project: Predictive Toxicology (PredTox)-overview and outcome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suter, Laura, E-mail: Laura.suter-dick@roche.com; Schroeder, Susanne; Meyer, Kirstin

    2011-04-15

    In this publication, we report the outcome of the integrated EU Framework 6 Project: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and 'omics' technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach ofmore » 'omics' and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that 'omics' technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated 'omics' analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.« less

  2. The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

    PubMed

    Bouffler, S D; Peters, S; Gilvin, P; Slack, K; Markiewicz, E; Quinlan, R A; Gillan, J; Coster, M; Barnard, S; Rothkamm, K; Ainsbury, E

    2015-06-01

    The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. Mechanism of Zn Insertion into Nanostructured δ-MnO 2 : A Nonaqueous Rechargeable Zn Metal Battery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Han, Sang-Don; Kim, Soojeong; Li, Dongguo

    2017-05-19

    Unlike the more established lithium-ion based energy storage chemistries, the complex intercalation chemistry of multivalent cations in a host lattice is not well understood, especially the relationship between the intercalating species solution chemistry and the prevalence and type of side reactions. Among multivalent metals, a promising model system can be based on nonaqueous Zn2+ ion chemistry. Several examples of these systems support the use of a Zn metal anode, and reversible intercalation cathodes have been reported. This study utilizes a combination of analytical tools to probe the chemistry of a nanostructured delta-MnO2 cathode in association with a nonaqueous acetonitrile-Zn(TFSI)(2) electrolytemore » and a Zn metal anode. As many of the issues related to understanding a multivalent battery relate to the electrolyte electrode interface, the high surface area of a nanostructured cathode provides a significant interface between the electrolyte and cathode host that maximizes the spectroscopic signal of any side reactions or minor mechanistic pathways. Numerous factors affecting capacity fade and issues associated with the second phase formation including Mn dissolution in heavily cycled Zn/delta-MnO2 cells are presented including dramatic mechanistic differences in the storage mechanism of this couple when compared to similar aqueous electrolytes are noted.« less

  4. Classification of spatially unresolved objects

    NASA Technical Reports Server (NTRS)

    Nalepka, R. F.; Horwitz, H. M.; Hyde, P. D.; Morgenstern, J. P.

    1972-01-01

    A proportion estimation technique for classification of multispectral scanner images is reported that uses data point averaging to extract and compute estimated proportions for a single average data point to classify spatial unresolved areas. Example extraction calculations of spectral signatures for bare soil, weeds, alfalfa, and barley prove quite accurate.

  5. Qualitative and quantitative assessment of Unresolved Complex Mixture in PM2.5 of Bakersfield, CA.

    EPA Science Inventory

    The 2010 CalNex (California Nexus) field experiment offered an opportunity for detailed characterization of atmospheric particulate carbon composition and sources in Bakersfield, CA. In the current study, the authors describe and employ a new protocol for reporting unresolved com...

  6. Approach to the hemodialysis patient with an abnormal serum bicarbonate concentration.

    PubMed

    Lisawat, Panupong; Gennari, F John

    2014-07-01

    We present a patient receiving hemodialysis with a persistently high serum bicarbonate concentration to illustrate the evaluation and management issues for patients with both high (>25 mEq/L) and low (<20 mEq/L) pretreatment values. Patients with high serum bicarbonate concentrations typically are malnourished and have low rates of endogenous acid production. Evaluation should begin with assessment of whether an acute and potentially reversible cause of metabolic alkalosis is present. If not, management should be directed at treating malnutrition. By contrast, patients with low predialysis serum bicarbonate concentrations, in the absence of an acute and reversible cause, may benefit from increasing the level by an adjustment in dialysate bicarbonate concentration. However, the level at which one should intervene and to what extent serum bicarbonate concentration should be increased are unresolved issues. Whether such an intervention will reduce mortality risk has not been determined. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  7. Signal Transduction: From the Atomic Age to the Post-Genomic Era

    PubMed Central

    Thorner, Jeremy; Hunter, Tony; Cantley, Lewis C.; Sever, Richard

    2014-01-01

    We have come a long way in the 55 years since Edmond Fischer and the late Edwin Krebs discovered that the activity of glycogen phosphorylase is regulated by reversible protein phosphorylation. Many of the fundamental molecular mechanisms that operate in biological signaling have since been characterized and the vast web of interconnected pathways that make up the cellular signaling network has been mapped in considerable detail. Nonetheless, it is important to consider how fast this field is still moving and the issues at the current boundaries of our understanding. One must also appreciate what experimental strategies have allowed us to attain our present level of knowledge. We summarize here some key issues (both conceptual and methodological), raise unresolved questions, discuss potential pitfalls, and highlight areas in which our understanding is still rudimentary. We hope these wide-ranging ruminations will be useful to investigators who carry studies of signal transduction forward during the rest of the 21st century. PMID:25359498

  8. The brain-computer interface cycle.

    PubMed

    van Gerven, Marcel; Farquhar, Jason; Schaefer, Rebecca; Vlek, Rutger; Geuze, Jeroen; Nijholt, Anton; Ramsey, Nick; Haselager, Pim; Vuurpijl, Louis; Gielen, Stan; Desain, Peter

    2009-08-01

    Brain-computer interfaces (BCIs) have attracted much attention recently, triggered by new scientific progress in understanding brain function and by impressive applications. The aim of this review is to give an overview of the various steps in the BCI cycle, i.e., the loop from the measurement of brain activity, classification of data, feedback to the subject and the effect of feedback on brain activity. In this article we will review the critical steps of the BCI cycle, the present issues and state-of-the-art results. Moreover, we will develop a vision on how recently obtained results may contribute to new insights in neurocognition and, in particular, in the neural representation of perceived stimuli, intended actions and emotions. Now is the right time to explore what can be gained by embracing real-time, online BCI and by adding it to the set of experimental tools already available to the cognitive neuroscientist. We close by pointing out some unresolved issues and present our view on how BCI could become an important new tool for probing human cognition.

  9. Remaining uncertainties in the use of Rn-222 as a quantitative tracer of submarine groundwater discharge

    USGS Publications Warehouse

    Burnett, W.C.; Santos, I.R.; Weinstein, Y.; Swarzenski, P.W.; Herut, B.

    2007-01-01

    Research performed in many locations over the past decade has shown that radon is an effective tracer for quantifying submarine groundwater discharge (SGD). The technique works because both fresh and saline groundwaters acquire radon from the subterranean environment and display activities that are typically orders of magnitude greater than those found in coastal seawaters. However, some uncertainties and unanswered problems remain. We focus here on three components of the mass balance, each of which has some unresolved issues: (1) End-member radon - what to do if groundwater Rn measurements are highly variable? (2) Atmospheric evasion -do the standard gas exchange equations work under high-energy coastal mixing scenarios? And (3) "mixing" losses - are there other significant radon losses (e.g. recharge of coastal waters into the aquifer) besides those attributed to mixing with lower-activity waters offshore? We address these issues using data sets collected from several different types of coastal environment. Copyright ?? 2007 IAHS Press.

  10. Translational systems biology using an agent-based approach for dynamic knowledge representation: An evolutionary paradigm for biomedical research.

    PubMed

    An, Gary C

    2010-01-01

    The greatest challenge facing the biomedical research community is the effective translation of basic mechanistic knowledge into clinically effective therapeutics. This challenge is most evident in attempts to understand and modulate "systems" processes/disorders, such as sepsis, cancer, and wound healing. Formulating an investigatory strategy for these issues requires the recognition that these are dynamic processes. Representation of the dynamic behavior of biological systems can aid in the investigation of complex pathophysiological processes by augmenting existing discovery procedures by integrating disparate information sources and knowledge. This approach is termed Translational Systems Biology. Focusing on the development of computational models capturing the behavior of mechanistic hypotheses provides a tool that bridges gaps in the understanding of a disease process by visualizing "thought experiments" to fill those gaps. Agent-based modeling is a computational method particularly well suited to the translation of mechanistic knowledge into a computational framework. Utilizing agent-based models as a means of dynamic hypothesis representation will be a vital means of describing, communicating, and integrating community-wide knowledge. The transparent representation of hypotheses in this dynamic fashion can form the basis of "knowledge ecologies," where selection between competing hypotheses will apply an evolutionary paradigm to the development of community knowledge.

  11. Mechanistic Biomarkers in Acetaminophen-induced Hepatotoxicity and Acute Liver Failure: From Preclinical Models to Patients

    PubMed Central

    McGill, Mitchell R.; Jaeschke, Hartmut

    2015-01-01

    SUMMARY Introduction Drug hepatotoxicity is a major clinical issue. Acetaminophen (APAP) overdose is especially common. Serum biomarkers used to follow patient progress reflect either liver injury or function, but focus on biomarkers that can provide insight into the basic mechanisms of hepatotoxicity is increasing and enabling us to translate mechanisms of toxicity from animal models to humans. Areas covered We review recent advances in mechanistic serum biomarker research in drug hepatotoxicity. Specifically, biomarkers for reactive drug intermdiates, mitochondrial dysfunction, nuclear DNA damage, mode of cell death and inflammation are discussed, as well as microRNAs. Emphasis is placed on APAP-induced liver injury. Expert Opinion Several serum biomarkers of reactive drug intermediates, mitochondrial damage, nuclear DNA damage, apoptosis and necrosis, and inflammation have been described. These studies have provided evidence that mitochondrial damage is critical in APAP hepatotoxicity in humans, while apoptosis has only a minor role, and inflammation is important for recovery and regeneration after APAP overdose. Additionally, mechanistic serum biomarkers have been shown to predict outcome as well as, or better than, some clinical scores. In the future, such biomarkers will help determine the need for liver transplantation and, with improved understanding of the human pathophysiology, identify novel therapeutic targets. PMID:24836926

  12. The American Indian Holocaust: Healing Historical Unresolved Grief.

    ERIC Educational Resources Information Center

    Brave Heart, Maria Yellow Horse; DeBruyn, Lemyra M.

    1998-01-01

    Argues for the existence of historical unresolved grief among American Indians. Outlines the historical legacy of war, genocide, and boarding schools resulting in intergenerational trauma and a host of associated social problems. Suggests healing strategies that integrate modern and traditional approaches to healing at the individual, family, and…

  13. 29 CFR 1691.10 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

  14. 29 CFR 1691.10 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

  15. 29 CFR 1691.10 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

  16. 29 CFR 1691.10 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

  17. 29 CFR 1691.10 - Agency enforcement of unresolved complaints.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

  18. Physician-Assisted Suicide and Euthanasia in the Intensive Care Unit: A Dialogue on Core Ethical Issues

    PubMed Central

    Goligher, Ewan C.; Ely, E. Wesley; Sulmasy, Daniel P.; Bakker, Jan; Raphael, John; Volandes, Angelo E.; Patel, Bhavesh M.; Payne, Kate; Hosie, Annmarie; Churchill, Larry; White, Douglas B.; Downar, James

    2016-01-01

    Objective Many patients are admitted to the intensive care unit at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia (PAS/E) holds implications for the practice of critical care medicine. The objective of this manuscript is to explore core ethical issues related to PAS/E from the perspective of healthcare professionals and ethicists on both sides of the debate. Synthesis We identified four issues highlighting the key areas of ethical tension central to evaluating PAS/E in medical practice: (1) the benefit or harm of death itself, (2) the relationship between PAS/E and withholding or withdrawing life support, (3) the morality of a physician deliberately causing death, and (4) the management of conscientious objection related to PAS/E in the critical care setting. We present areas of common ground as well as important unresolved differences. Conclusions We reached differing positions on the first three core ethical questions and achieved significant agreement on how critical care clinicians should manage conscientious objections related to PAS/E. The alternative positions presented in this paper may serve to promote open and informed dialogue within the critical care community. PMID:28098622

  19. Proceedings of the Hydrokinetic and Wave Energy Technologies Technical and Environmental Issues Workshop

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    None

    2006-03-01

    Renewable energy technologies offer the promise of non-polluting alternatives to fossil and nuclear-fueled power plants to meet growing demand for electrical energy. Two emerging categories of renewable energy technologies, hydrokinetic and wave energy conversion devices, offer ways to tap the energy of moving water without impoundment (dams) or diversion required by many conventional hydroelectric facilities. These technologies include devices designed for deployment in natural streams, tidal estuaries, ocean currents, and constructed waterways, as well as devices designed to capture the energy of ocean waves. On October 26-28, 2005, 54 representatives from government, non-governmental organizations, and private business met to (1)more » identify the varieties of hydrokinetic energy and wave technology devices, their stages of development, and the projected cost to bring each to market; (2) identify where these technologies can best operate; (3) identify the potential environmental issues associated with these technologies and possible mitigation measures; (4) develop a list of research needs and/or practical solutions to address unresolved environmental issues. These workshop proceedings include detailed summaries of the 24 presentations made and the discussions that followed.« less

  20. Advantages and Challenges of Radiative Liquid Lithium Divertor

    NASA Astrophysics Data System (ADS)

    Ono, Masayuki

    2017-10-01

    Steady-state fusion power plant designs present major divertor technology challenges, including high divertor heat flux both in steady-state and during transients. In addition to these concerns, there are the unresolved technology issues of long term dust accumulation and associated tritium inventory and safety issues. The application of lithium (Li) in NSTX resulted in improved H-mode confinement, H-mode power threshold reduction, and reduction in the divertor peak heat flux while maintaining essentially Li-free core plasma operation even during H-modes. These promising results in NSTX and related modeling calculations motivated the radiative liquid Li divertor (RLLD) concept and its variant, the active liquid Li divertor concept (ARLLD), taking advantage of the enhanced Li radiation in relatively poorly confined divertor plasmas. It has been suggested that radiation-based liquid lithium (LL) divertor concepts with a modest Li-loop could provide a possible solution for the outstanding fusion reactor technology issues such as divertor heat flux mitigation and real time dust removal, while potentially improving the reactor plasma performance. Laboratory tests are also planned to investigate the Li-T recover efficiency and other relevant research topics of the RLLD. This work supported by DoE Contract No. DE-AC02-09CH11466.

  1. Physician-Assisted Suicide and Euthanasia in the ICU: A Dialogue on Core Ethical Issues.

    PubMed

    Goligher, Ewan C; Ely, E Wesley; Sulmasy, Daniel P; Bakker, Jan; Raphael, John; Volandes, Angelo E; Patel, Bhavesh M; Payne, Kate; Hosie, Annmarie; Churchill, Larry; White, Douglas B; Downar, James

    2017-02-01

    Many patients are admitted to the ICU at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia holds implications for the practice of critical care medicine. The objective of this article is to explore core ethical issues related to physician-assisted suicide and euthanasia from the perspective of healthcare professionals and ethicists on both sides of the debate. We identified four issues highlighting the key areas of ethical tension central to evaluating physician-assisted suicide and euthanasia in medical practice: 1) the benefit or harm of death itself, 2) the relationship between physician-assisted suicide and euthanasia and withholding or withdrawing life support, 3) the morality of a physician deliberately causing death, and 4) the management of conscientious objection related to physician-assisted suicide and euthanasia in the critical care setting. We present areas of common ground and important unresolved differences. We reached differing positions on the first three core ethical questions and achieved unanimity on how critical care clinicians should manage conscientious objections related to physician-assisted suicide and euthanasia. The alternative positions presented in this article may serve to promote open and informed dialogue within the critical care community.

  2. Invariant natural killer T cells trigger adaptive lymphocytes to churn up bile.

    PubMed

    Joyce, Sebastian; Van Kaer, Luc

    2008-05-15

    How innate immune response causes autoimmunity has remained an enigma. In this issue of Cell Host & Microbe, Mattner et al. demonstrate that invariant natural killer T cells activated by the mucosal commensal Novosphingobium aromaticivorans precipitate chronic T cell-mediated autoimmunity against small bile ducts that mirrors human primary biliary cirrhosis. These findings provide a mechanistic understanding of the role of innate immunity toward a microbe in the development of autoimmunity.

  3. Mechanistic origin and prediction of enhanced ductility in magnesium alloys

    NASA Astrophysics Data System (ADS)

    Wu, Zhaoxuan; Ahmad, Rasool; Yin, Binglun; Sandlöbes, Stefanie; Curtin, W. A.

    2018-01-01

    Development of ductile magnesium alloys is key to their use in reducing the weight of vehicles and other applications. Wu et al. tackle this issue by determining the underlying mechanisms in unprocessed magnesium alloys. Dilute amounts of solutes enhanced certain ductility-improving mechanisms over ones that cause brittle fracture. From this, the authors developed a theory that may be helpful for screening the large number of potential magnesium alloy compositions.

  4. Unresolved Loss, a Risk Factor for Offspring, Predicts Event-Related Potential Responses to Death-Related Imagery

    ERIC Educational Resources Information Center

    Bahm, Naomi I. Gribneau; Simon-Thomas, Emiliana R.; Main, Mary; Hesse, Erik

    2017-01-01

    This study investigates whether individual differences in attachment status can be detected by electrophysiological responses to loss-themed pictures. The Adult Attachment Interview (AAI) was used to identify discourse/reasoning lapses during the discussion of loss experiences via death that place speakers in the Unresolved/disorganized AAI…

  5. Development of an Art Psychotherapy Model for the Prevention and Treatment of Unresolved Grief during Midlife.

    ERIC Educational Resources Information Center

    Turetsky, Cheryl J.; Hays, Ronald E.

    2003-01-01

    Presents an integrated model as an appropriate intervention to enable mourning and creativity and thus help in the prevention and treatment of unresolved grief in midlife. Two examples of this model in art-psychotherapy group treatment are provided. (Contains 53 references, 1 table, and 2 figures.) (GCP)

  6. Unresolved Attachment, PTSD, and Dissociation in Women with Childhood Abuse Histories

    ERIC Educational Resources Information Center

    Stovall-McClough, K. Chase; Cloitre, Marylene

    2006-01-01

    The primary objective of this study was to examine unresolved trauma as assessed by the Adult Attachment Interview and current psychiatric symptoms, focusing on posttraumatic stress disorder (PTSD) and dissociation, in a group of adult female childhood abuse survivors. The authors examined psychiatric symptoms and attachment representations in a…

  7. Observation of Unresolved Features in the Microwave Sky

    NASA Astrophysics Data System (ADS)

    Kowitt, M. S.; Cheng, E. S.; Cottingham, D. A.; Fixsen, D. J.; Silverberg, R. F.; Inman, C. A.; Meyer, S. S.; Puchalla, J. L.; Ruhl, J. E.; Page, L. A.

    1994-12-01

    We report on the detection of unresolved features in broadband observations from 5.6 to 22.5 cm(-1) with a 0\\fdg5 beam by the Medium Scale Anisotropy Measurement (Cheng et al. 1994, ApJ, 422, L37). Spectra for the features will be presented, along with a discussion of their possible origin.

  8. 47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

  9. 47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

  10. 47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

  11. 2007 TOXICOLOGY AND RISK ASSESSMENT ...

    EPA Pesticide Factsheets

    EPA has announced The 2007 Toxicology and Risk Assessment Conference Cincinnati Marriott North, West Chester (Cincinnati), OHApril 23- 26, 2007 - Click to register!The Annual Toxicology and Risk Assessment Conference is a unique meeting where several Government Agencies come together to discuss toxicology and risk assessment issues that are not only of concern to the government, but also to a broader audience including academia and industry. The theme of this year's conference is Emerging Issues and Challenges in Risk Assessment and the preliminary agenda includes: Plenary Sessions and prominent speakers (tentative) include: Issues of Emerging Chemical ContaminantsUncertainty and Variability in Risk Assessment Use of Mechanistic data in IARC evaluationsParallel Sessions:Uncertainty and Variability in Dose-Response Assessment Recent Advances in Toxicity and Risk Assessment of RDX The Use of Epidemiologic Data for Risk Assessment Applications Cumulative Health Risk Assessment:

  12. Speckle imaging of active galactic nuclei: NGC 1068 and NGC 4151

    NASA Astrophysics Data System (ADS)

    Ebstein, Steven Michael

    High resolution images of NGC 1068 and NGC 4151 in the 5007 A line and the nearby continuum produced from data taken with the PAPA photon counting imaging detector using the technique of speckle imaging are presented. The images show an unresolved core of 5007 A emission in the middle of an extended emission region. The extended emission tends to lie alongside the subarcsecond radio structure. In NGC 4151, the extended emission comes from a nearly linear structure extending on both sides of the unresolved core. In NGC 1068, the extended emission is concentrated in lobes lying to the unresolved core but the emission is concentrated in lobes lying to either side of the major axis. The continuum of NGC 4151 is spatially unresolved. The continuum of NGC 1068 is extended approx. 1 in to the SW of the center of the 5007 A emission. Certain aspects of the PAPA detector are discussed, including the variable threshold discriminators that track the image intensifier pulse height and the camera artifacts. The data processing is described in detail.

  13. New Theoretical Estimates of the Contribution of Unresolved Star-Forming Galaxies to the Extragalactic Gamma-Ray Background (EGB) as Measured by EGRET and the Fermi-LAT

    NASA Technical Reports Server (NTRS)

    Venters, Tonia M.

    2011-01-01

    We present new theoretical estimates of the contribution of unresolved star-forming galaxies to the extragalactic gamma-ray background (EGB) as measured by EGRET and the Fermi-LAT. We employ several methods for determining the star-forming galaxy contribution the the EGB, including a method positing a correlation between the gamma-ray luminosity of a galaxy and its rate of star formation as calculated from the total infrared luminosity, and a method that makes use of a model of the evolution of the galaxy gas mass with cosmic time. We find that depending on the model, unresolved star-forming galaxies could contribute significantly to the EGB as measured by the Fermi-LAT at energies between approx. 300 MeV and approx. few GeV. However, the overall spectrum of unresolved star-forming galaxies can explain neither the EGRET EGB spectrum at energies between 50 and 200 MeV nor the Fermi-LAT EGB spectrum at energies above approx. few GeV.

  14. Fistulizing Crohn's disease: Diagnosis and management.

    PubMed

    Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter; D'Haens, Geert

    2013-06-01

    Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.

  15. Artificial organs: recent progress in artificial hearing and vision.

    PubMed

    Ifukube, Tohru

    2009-01-01

    Artificial sensory organs are a prosthetic means of sending visual or auditory information to the brain by electrical stimulation of the optic or auditory nerves to assist visually impaired or hearing-impaired people. However, clinical application of artificial sensory organs, except for cochlear implants, is still a trial-and-error process. This is because how and where the information transmitted to the brain is processed is still unknown, and also because changes in brain function (plasticity) remain unknown, even though brain plasticity plays an important role in meaningful interpretation of new sensory stimuli. This article discusses some basic unresolved issues and potential solutions in the development of artificial sensory organs such as cochlear implants, brainstem implants, artificial vision, and artificial retinas.

  16. Care of the Chronically Ill at Home: An Unresolved Dilemma in Health Policy for the United States

    PubMed Central

    Buhler-Wilkerson, Karen

    2007-01-01

    The problems of caring for patients with disabling illnesses who neither get well nor die are not new. Such patients have always required assistance at home from family, benevolent volunteers, or paid caregivers. Despite two centuries of experimentation, however, no agreement exists concerning the balance between the public and private resources to be allocated through state funding, private insurance, and family contributions for the daily and routine care at home for chronically ill persons of all ages. This article examines these issues and the unavoidable tensions between fiscal reality and legitimate need. It also uses historical and policy analyses to explain why home care has never become the cornerstone for caring for the chronically ill. PMID:18070332

  17. Chapter 3. A multidimensional model for narrative analysis of substance use-related dependency.

    PubMed

    Larsson, Sam; von Braun, Therese; Lilja, John

    2013-11-01

    This chapter examines the possibilities and limitations of using a narrative method as a framework within a multidimensional model for exploring and analyzing the use and misuse of alcohol and drugs. It is posited that a multidimensional model, based on narrative reasoning, can give a more detailed and specific understanding of substance users, who represent a heterogeneous population of people, and of substance use-related dependency problems. Such a model describes and analyses the drug-use related problems in a manner that provides holistic and important information and knowledge about the person by contextual and situation interaction processes which are involved in the use/misuse of alcohol and drugs. Tentative conclusions and unresolved critical issues are considered.

  18. What can we learn from fitness landscapes?

    PubMed

    Hartl, Daniel L

    2014-10-01

    A combinatorially complete data set consists of studies of all possible combinations of a set of mutant sites in a gene or mutant alleles in a genome. Among the most robust conclusions from these studies is that epistasis between beneficial mutations often shows a pattern of diminishing returns, in which favorable mutations are less fit when combined than would be expected. Another robust inference is that the number of adaptive evolutionary paths is often limited to a relatively small fraction of the theoretical possibilities, owing largely to sign epistasis requiring evolutionary steps that would entail a decrease in fitness. Here we summarize these and other results while also examining issues that remain unresolved and future directions that seem promising. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Ethics in American health 1: ethical approaches to health policy.

    PubMed

    Ruger, Jennifer Prah

    2008-10-01

    I trace the evolution of ethical approaches to health policy in the United States and examine a number of critical unresolved issues pertaining to the current set of frameworks. Several themes emerge. First, fair procedures claim more attention than substantive and procedural principles. Second, in the case of public deliberation, more focus has been placed on factors such as procedural mechanisms than on understanding how individuals and groups value different aspects of health and agree on health-related decisions. Third, the nation needs workable frameworks to guide collective choices about valuable social ends and their trade-offs; purely procedural strategies are limited in illuminating overarching health policy and ethics questions. There is a need to integrate consequential and procedural approaches to health ethics and policy.

  20. Reconsidering reflexivity: introducing the case for intellectual entrepreneurship.

    PubMed

    Cutcliffe, John R

    2003-01-01

    In this article, the author reconsiders reflexivity and attempts to examine some unresolved issues by drawing particular attention to the relationship between reflexivity and certain related phenomena/processes: the researcher's a priori knowledge, values, beliefs; empathy within qualitative research; the presence and influence of the researcher's tacit knowledge, and May's "magic" in method. Given the limitations of some reflexive activity identified in this article, the author introduces the case for greater intellectual entrepreneurship within the context of qualitative research. He suggests that excessive emphasis on reflexive activity might inhibit intellectual entrepreneurship. Wherein intellectual entrepreneurship implies a conscious and deliberate attempt on the part of academics to explore the world of ideas boldly; to take more risks in theory development and to move away from being timid researchers.

  1. Novel Tactile Sensor Technology and Smart Tactile Sensing Systems: A Review

    PubMed Central

    Ge, Chang; Wang, Z. Jane; Cretu, Edmond; Li, Xiaoou

    2017-01-01

    During the last decades, smart tactile sensing systems based on different sensing techniques have been developed due to their high potential in industry and biomedical engineering. However, smart tactile sensing technologies and systems are still in their infancy, as many technological and system issues remain unresolved and require strong interdisciplinary efforts to address them. This paper provides an overview of smart tactile sensing systems, with a focus on signal processing technologies used to interpret the measured information from tactile sensors and/or sensors for other sensory modalities. The tactile sensing transduction and principles, fabrication and structures are also discussed with their merits and demerits. Finally, the challenges that tactile sensing technology needs to overcome are highlighted. PMID:29149080

  2. Brain responses to filled gaps.

    PubMed

    Hestvik, Arild; Maxfield, Nathan; Schwartz, Richard G; Shafer, Valerie

    2007-03-01

    An unresolved issue in the study of sentence comprehension is whether the process of gap-filling is mediated by the construction of empty categories (traces), or whether the parser relates fillers directly to the associated verb's argument structure. We conducted an event-related potentials (ERP) study that used the violation paradigm to examine the time course and spatial distribution of brain responses to ungrammatically filled gaps. The results indicate that the earliest brain response to the violation is an early left anterior negativity (eLAN). This ERP indexes an early phase of pure syntactic structure building, temporally preceding ERPs that reflect semantic integration and argument structure satisfaction. The finding is interpreted as evidence that gap-filling is mediated by structurally predicted empty categories, rather than directly by argument structure operations.

  3. Setting the stage for habitable planets.

    PubMed

    Gonzalez, Guillermo

    2014-02-21

    Our understanding of the processes that are relevant to the formation and maintenance of habitable planetary systems is advancing at a rapid pace, both from observation and theory. The present review focuses on recent research that bears on this topic and includes discussions of processes occurring in astrophysical, geophysical and climatic contexts, as well as the temporal evolution of planetary habitability. Special attention is given to recent observations of exoplanets and their host stars and the theories proposed to explain the observed trends. Recent theories about the early evolution of the Solar System and how they relate to its habitability are also summarized. Unresolved issues requiring additional research are pointed out, and a framework is provided for estimating the number of habitable planets in the Universe.

  4. ECASTAR: Energy conservation. An assessment of systems, technologies and requirements

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A methodology was presented for a systems approach to energy conservation actions and their potentials and impacts in the United States. Constraints affecting the approach were ranked, and the most important ones are the present economic and technical conditions. The following unresolved issues were identified: consumptive lifestyles vs. conservation ethic, environmental standards vs. energy conservation, capital availability, decentralization and vertical integration vs. centralization, fuel rich regions vs. fuel poor regions, supply vs. end use conservation, life cycle costing vs. initial cost, mandatory savings vs. voluntary savings, labor intensive vs. capital intensive, price control vs. free market. The following recommendations were made: provide action/impact assessment, establish regional energy centers, improve technology articulation with government, design total energy systems, utilize existing systems approach expertise.

  5. Healthcare decisions: a review of children's involvement.

    PubMed

    Baston, Jenny

    2008-04-01

    Children's rights, their ability to consent to treatment and their involvement in healthcare decisions have received considerable attention in recent years. There is some evidence to suggest that when children are involved in the decision-making process, they retain a sense of control over their situation. However there are still unresolved issues related to a child's right to decide and nurses may be confused about the extent to which children can and should be involved in decision-making. A code of practice for involving children in decisions was first suggested in 2001 and there is still a need for a consistent, structured and robust method of ensuring that children are included in the decision-making process at all stages of their health care.

  6. Setting the Stage for Habitable Planets

    PubMed Central

    Gonzalez, Guillermo

    2014-01-01

    Our understanding of the processes that are relevant to the formation and maintenance of habitable planetary systems is advancing at a rapid pace, both from observation and theory. The present review focuses on recent research that bears on this topic and includes discussions of processes occurring in astrophysical, geophysical and climatic contexts, as well as the temporal evolution of planetary habitability. Special attention is given to recent observations of exoplanets and their host stars and the theories proposed to explain the observed trends. Recent theories about the early evolution of the Solar System and how they relate to its habitability are also summarized. Unresolved issues requiring additional research are pointed out, and a framework is provided for estimating the number of habitable planets in the Universe. PMID:25370028

  7. Stationarity: Wanted dead or alive?

    USGS Publications Warehouse

    Lins, Larry F.; Cohn, Timothy A.

    2011-01-01

    Aligning engineering practice with natural process behavior would appear, on its face, to be a prudent and reasonable course of action. However, if we do not understand the long-term characteristics of hydroclimatic processes, how does one find the prudent and reasonable course needed for water management? We consider this question in light of three aspects of existing and unresolved issues affecting hydroclimatic variability and statistical inference: Hurst-Kolmogorov phenomena; the complications long-term persistence introduces with respect to statistical understanding; and the dependence of process understanding on arbitrary sampling choices. These problems are not easily addressed. In such circumstances, humility may be more important than physics; a simple model with well-understood flaws may be preferable to a sophisticated model whose correspondence to reality is uncertain.

  8. Unresolved versus resolved: testing the validity of young simple stellar population models with VLT/MUSE observations of NGC 3603

    NASA Astrophysics Data System (ADS)

    Kuncarayakti, H.; Galbany, L.; Anderson, J. P.; Krühler, T.; Hamuy, M.

    2016-09-01

    Context. Stellar populations are the building blocks of galaxies, including the Milky Way. The majority, if not all, extragalactic studies are entangled with the use of stellar population models given the unresolved nature of their observation. Extragalactic systems contain multiple stellar populations with complex star formation histories. However, studies of these systems are mainly based upon the principles of simple stellar populations (SSP). Hence, it is critical to examine the validity of SSP models. Aims: This work aims to empirically test the validity of SSP models. This is done by comparing SSP models against observations of spatially resolved young stellar population in the determination of its physical properties, that is, age and metallicity. Methods: Integral field spectroscopy of a young stellar cluster in the Milky Way, NGC 3603, was used to study the properties of the cluster as both a resolved and unresolved stellar population. The unresolved stellar population was analysed using the Hα equivalent width as an age indicator and the ratio of strong emission lines to infer metallicity. In addition, spectral energy distribution (SED) fitting using STARLIGHT was used to infer these properties from the integrated spectrum. Independently, the resolved stellar population was analysed using the colour-magnitude diagram (CMD) to determine age and metallicity. As the SSP model represents the unresolved stellar population, the derived age and metallicity were tested to determine whether they agree with those derived from resolved stars. Results: The age and metallicity estimate of NGC 3603 derived from integrated spectroscopy are confirmed to be within the range of those derived from the CMD of the resolved stellar population, including other estimates found in the literature. The result from this pilot study supports the reliability of SSP models for studying unresolved young stellar populations. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 60.A-9344.

  9. An Image-based Micro-continuum Pore-scale Model for Gas Transport in Organic-rich Shale

    NASA Astrophysics Data System (ADS)

    Guo, B.; Tchelepi, H.

    2017-12-01

    Gas production from unconventional source rocks, such as ultra-tight shales, has increased significantly over the past decade. However, due to the extremely small pores ( 1-100 nm) and the strong material heterogeneity, gas flow in shale is still not well understood and poses challenges for predictive field-scale simulations. In recent years, digital rock analysis has been applied to understand shale gas transport at the pore-scale. An issue with rock images (e.g. FIB-SEM, nano-/micro-CT images) is the so-called "cutoff length", i.e., pores and heterogeneities below the resolution cannot be resolved, which leads to two length scales (resolved features and unresolved sub-resolution features) that are challenging for flow simulations. Here we develop a micro-continuum model, modified from the classic Darcy-Brinkman-Stokes framework, that can naturally couple the resolved pores and the unresolved nano-porous regions. In the resolved pores, gas flow is modeled with Stokes equation. In the unresolved regions where the pore sizes are below the image resolution, we develop an apparent permeability model considering non-Darcy flow at the nanoscale including slip flow, Knudsen diffusion, adsorption/desorption, surface diffusion, and real gas effect. The end result is a micro-continuum pore-scale model that can simulate gas transport in 3D reconstructed shale images. The model has been implemented in the open-source simulation platform OpenFOAM. In this paper, we present case studies to demonstrate the applicability of the model, where we use 3D segmented FIB-SEM and nano-CT shale images that include four material constituents: organic matter, clay, granular mineral, and pore. In addition to the pore structure and the distribution of the material constituents, we populate the model with experimental measurements (e.g. size distribution of the sub-resolution pores from nitrogen adsorption) and parameters from the literature and identify the relative importance of different physics on gas production. Overall, the micro-continuum model provides a novel tool for digital rock analysis of organic-rich shale.

  10. A Comparison of Unresolved Versus Resolved Status and Its Relationship to Behaviour in Maltreated Adolescents

    ERIC Educational Resources Information Center

    Webster, Linda; Hackett, Rachelle Kisst

    2007-01-01

    This exploratory investigation sought both to gain a better understanding of the mental representations of attachment in high-risk, maltreated adolescents and to explain how, if at all, unresolved attachment representations are related to behavioural maladjustment. Parent ratings, self-report ratings and attachment state of mind were obtained from…

  11. NATURE OF UNRESOLVED COMPLEX MIXTURE IN SIZE-DISTRIBUTED EMISSIONS FROM RESIDENTIAL WOOD COMBUSTION AS MEASURED BY THERMAL DESORPTION-GAS CHROMATOGRAPHY-MASS SPECTROMETRY

    EPA Science Inventory

    In this study, the unresolved complex mixture (UCM) in size resolved fine aerosol emissions from residential wood combustion (RWC) is examined. The aerosols are sorted by size in an electrical low-pressure impactor (ELPI) and subsequently analyzed by thermal desorbtion/gas chroma...

  12. A subtraction scheme for computing QCD jet cross sections at NNLO: integrating the iterated singly-unresolved subtraction terms

    NASA Astrophysics Data System (ADS)

    Bolzoni, Paolo; Somogyi, Gábor; Trócsányi, Zoltán

    2011-01-01

    We perform the integration of all iterated singly-unresolved subtraction terms, as defined in ref. [1], over the two-particle factorized phase space. We also sum over the unresolved parton flavours. The final result can be written as a convolution (in colour space) of the Born cross section and an insertion operator. We spell out the insertion operator in terms of 24 basic integrals that are defined explicitly. We compute the coefficients of the Laurent expansion of these integrals in two different ways, with the method of Mellin-Barnes representations and sector decomposition. Finally, we present the Laurent-expansion of the full insertion operator for the specific examples of electron-positron annihilation into two and three jets.

  13. Rapid radiation events in the family Ursidae indicated by likelihood phylogenetic estimation from multiple fragments of mtDNA.

    PubMed

    Waits, L P; Sullivan, J; O'Brien, S J; Ward, R H

    1999-10-01

    The bear family (Ursidae) presents a number of phylogenetic ambiguities as the evolutionary relationships of the six youngest members (ursine bears) are largely unresolved. Recent mitochondrial DNA analyses have produced conflicting results with respect to the phylogeny of ursine bears. In an attempt to resolve these issues, we obtained 1916 nucleotides of mitochondrial DNA sequence data from six gene segments for all eight bear species and conducted maximum likelihood and maximum parsimony analyses on all fragments separately and combined. All six single-region gene trees gave different phylogenetic estimates; however, only for control region data was this significantly incongruent with the results from the combined data. The optimal phylogeny for the combined data set suggests that the giant panda is most basal followed by the spectacled bear. The sloth bear is the basal ursine bear, and there is weak support for a sister taxon relationship of the American and Asiatic black bears. The sun bear is sister taxon to the youngest clade containing brown bears and polar bears. Statistical analyses of alternate hypotheses revealed a lack of strong support for many of the relationships. We suggest that the difficulties surrounding the resolution of the evolutionary relationships of the Ursidae are linked to the existence of sequential rapid radiation events in bear evolution. Thus, unresolved branching orders during these time periods may represent an accurate representation of the evolutionary history of bear species. Copyright 1999 Academic Press.

  14. Solar Coronal UV Spectroscopy for Solar Wind and SEP Acceleration Investigations

    NASA Astrophysics Data System (ADS)

    Moses, John Daniel; Ko, Yuan-Kuen; Laming, John Martin; Strachan, Leonard; Tun Beltran, Samuel

    2015-04-01

    Of all the new areas of solar physics opened by the landmark SOHO mission, the scientific discoveries of the Ultraviolet Coronagraph Spectrometer (UVCS) are unique in both the importance of the new questions raised by these observations and the lack of subsequent investigations to resolve these questions. For example, the first direct evidence of wave-particle coupling as an acceleration mechanism for the solar wind was obtained from UVCS spectro-coronagraphic observations, yet the real limits on the ratio of the parallel to perpendicular ion temperatures (with respect to the magnetic field) in coronal holes and streamers is still unresolved. Another unresolved issue is the role of suprathermal seed particles in rapid diffusive shock acceleration of SEPs. Although the theory has been placed on firmer theoretical ground by recent in situ investigations, observations of these suprathermal particles in the corona was never conclusively obtained with UVCS.Any follow-on UV Spectro-coronagraph must possess two improvements over UVCS in order to address the questions raised during the SOHO mission: 1) increased effective aperture and 2) improved spectrographic contrast (i.e. reduced scattered light). Technological developments in optics, optical design, UV detectors, composite structures, cleanliness control and electronics make it possible to achieve the requisite improvements in a next-generation UV spectro-coronagraph within the constraints of an affordable mission. We discuss specific instrument and mission approaches developed over the last 5 years and the feasibility of implementing them within the next 5 years.

  15. Solar Coronal UV Spectroscopy for Solar Wind and Sep Acceleration Investigations

    NASA Astrophysics Data System (ADS)

    Moses, J. D.; Laming, J. M.; Ko, Y. K.; Strachan, L.

    2014-12-01

    Of all the new areas of solar physics opened by the landmark SOHO mission, the scientific discoveries of the Ultraviolet Coronagraph Spectrometer (UVCS) are unique in both the importance of the new questions raised by these observations and the lack of subsequent investigations to resolve these questions. For example, the first direct evidence of wave-particle coupling as an acceleration mechanism for the solar wind was obtained from UVCS spectro-coronagraphic observations, yet the real limits on the ratio of the parallel to perpendicular ion temperatures (with respect to the magnetic field) in coronal holes and streamers is still unresolved. Another unresolved issue is the role of suprathermal seed particles in rapid diffusive shock acceleration of SEPs. Although the theory has been placed on firmer theoretical ground by recent in situinvestigations, observations of these suprathermal particles in the corona were never conclusively obtained with UVCS. Any follow-on UV Spectro-coronagraph must possess two improvements over UVCS in order to address the questions raised during the SOHO mission: 1) increased effective aperture and 2) improved spectrographic contrast (i.e. reduced scattered light). Technological developments in optics, optical design, UV detectors, composite structures, cleanliness control and electronics make it possible to achieve the requisite improvements in a next-generation UV spectro-coronagraph within the constraints of an affordable mission. We discuss specific instrument and mission approaches developed over the last 5 years and the feasibility of implementing them within the next 5 years.

  16. A framework for testing and comparing binaural models.

    PubMed

    Dietz, Mathias; Lestang, Jean-Hugues; Majdak, Piotr; Stern, Richard M; Marquardt, Torsten; Ewert, Stephan D; Hartmann, William M; Goodman, Dan F M

    2018-03-01

    Auditory research has a rich history of combining experimental evidence with computational simulations of auditory processing in order to deepen our theoretical understanding of how sound is processed in the ears and in the brain. Despite significant progress in the amount of detail and breadth covered by auditory models, for many components of the auditory pathway there are still different model approaches that are often not equivalent but rather in conflict with each other. Similarly, some experimental studies yield conflicting results which has led to controversies. This can be best resolved by a systematic comparison of multiple experimental data sets and model approaches. Binaural processing is a prominent example of how the development of quantitative theories can advance our understanding of the phenomena, but there remain several unresolved questions for which competing model approaches exist. This article discusses a number of current unresolved or disputed issues in binaural modelling, as well as some of the significant challenges in comparing binaural models with each other and with the experimental data. We introduce an auditory model framework, which we believe can become a useful infrastructure for resolving some of the current controversies. It operates models over the same paradigms that are used experimentally. The core of the proposed framework is an interface that connects three components irrespective of their underlying programming language: The experiment software, an auditory pathway model, and task-dependent decision stages called artificial observers that provide the same output format as the test subject. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

    PubMed

    Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

    2018-05-31

    Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Resource diversity and provenance underpin spatial patterns in functional diversity across native and exotic species.

    PubMed

    Méndez, Verónica; Wood, Jamie R; Butler, Simon J

    2018-05-01

    Functional diversity metrics are increasingly used to augment or replace taxonomic diversity metrics to deliver more mechanistic insights into community structure and function. Metrics used to describe landscape structure and characteristics share many of the same limitations as taxonomy-based metrics, particularly their reliance on anthropogenically defined typologies with little consideration of structure, management, or function. However, the development of alternative metrics to describe landscape characteristics has been limited. Here, we extend the functional diversity framework to characterize landscapes based on the diversity of resources available across habitats present. We then examine the influence of resource diversity and provenance on the functional diversities of native and exotic avian communities in New Zealand. Invasive species are increasingly prevalent and considered a global threat to ecosystem function, but the characteristics of and interactions between sympatric native and exotic communities remain unresolved. Understanding their comparative responses to environmental change and the mechanisms underpinning them is of growing importance in predicting community dynamics and changing ecosystem function. We use (i) matrices of resource use (species) and resource availability (habitats) and (ii) occurrence data for 62 native and 25 exotic species and 19 native and 13 exotic habitats in 2015 10 × 10 km quadrats to examine the relationship between native and exotic avian and landscape functional diversity. The numbers of species in, and functional diversities of, native and exotic communities were positively related. Each community displayed evidence of environmental filtering, but it was significantly stronger for exotic species. Less environmental filtering occurred in landscapes providing a more diverse combination of resources, with resource provenance also an influential factor. Landscape functional diversity explained a greater proportion of variance in native and exotic community characteristics than the number of habitat types present. Resource diversity and provenance should be explicitly accounted for when characterizing landscape structure and change as they offer additional mechanistic understanding of the links between environmental filtering and community structure. Manipulating resource diversity through the design and implementation of management actions could prove a powerful tool for the delivery of conservation objectives, be they to protect native species, control exotic species, or maintain ecosystem service provision.

  19. Tree-Level Hydrodynamic Approach for Improved Stomatal Conductance Parameterization

    NASA Astrophysics Data System (ADS)

    Mirfenderesgi, G.; Bohrer, G.; Matheny, A. M.; Ivanov, V. Y.

    2014-12-01

    The land-surface models do not mechanistically resolve hydrodynamic processes within the tree. The Finite-Elements Tree-Crown Hydrodynamics model version 2 (FETCH2) is based on the pervious FETCH model approach, but with finite difference numerics, and simplified single-beam conduit system. FETCH2 simulates water flow through the tree as a simplified system of porous media conduits. It explicitly resolves spatiotemporal hydraulic stresses throughout the tree's vertical extent that cannot be easily represented using other stomatal-conductance models. Empirical equations relate water potential at the stem to stomata conductance at leaves connected to the stem (through unresolved branches) at that height. While highly simplified, this approach bring some realism to the simulation of stomata conductance because the stomata can respond to stem water potential, rather than an assumed direct relationship with soil moisture, as is currently the case in almost all models. By enabling mechanistic simulation of hydrological traits, such as xylem conductivity, conductive area per DBH, vertical distribution of leaf area and maximal and minimal water content in the xylem, and their effect of the dynamics of water flow in the tree system, the FETCH2 modeling system enhanced our understanding of the role of hydraulic limitations on an experimental forest plot short-term water stresses that lead to tradeoffs between water and light availability for transpiring leaves in forest ecosystems. FETCH2 is particularly suitable to resolve the effects of structural differences between tree and species and size groups, and the consequences of differences in hydraulic strategies of different species. We leverage on a large dataset of sap flow from 60 trees of 4 species at our experimental plot at the University of Michigan Biological Station. Comparison of the sap flow and transpiration patterns in this site and an undisturbed control site shows significant difference in hydraulic strategies between species which affect their response to the disturbance. We used FETCH2 to conduct a sensitivity analysis of the total stand-level transpiration to the inter-specific differences in hydraulic strategies and used the results to reflect on the future trajectory of the forest, in terms of species composition and transpiration.

  20. Real versus Artificial Variation in the Thermal Sensitivity of Biological Traits.

    PubMed

    Pawar, Samraat; Dell, Anthony I; Savage, Van M; Knies, Jennifer L

    2016-02-01

    Whether the thermal sensitivity of an organism's traits follows the simple Boltzmann-Arrhenius model remains a contentious issue that centers around consideration of its operational temperature range and whether the sensitivity corresponds to one or a few underlying rate-limiting enzymes. Resolving this issue is crucial, because mechanistic models for temperature dependence of traits are required to predict the biological effects of climate change. Here, by combining theory with data on 1,085 thermal responses from a wide range of traits and organisms, we show that substantial variation in thermal sensitivity (activation energy) estimates can arise simply because of variation in the range of measured temperatures. Furthermore, when thermal responses deviate systematically from the Boltzmann-Arrhenius model, variation in measured temperature ranges across studies can bias estimated activation energy distributions toward higher mean, median, variance, and skewness. Remarkably, this bias alone can yield activation energies that encompass the range expected from biochemical reactions (from ~0.2 to 1.2 eV), making it difficult to establish whether a single activation energy appropriately captures thermal sensitivity. We provide guidelines and a simple equation for partially correcting for such artifacts. Our results have important implications for understanding the mechanistic basis of thermal responses of biological traits and for accurately modeling effects of variation in thermal sensitivity on responses of individuals, populations, and ecological communities to changing climatic temperatures.

  1. Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology.

    PubMed

    Verma, Mukesh

    2017-04-01

    This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

  2. Mechanism of Zn Insertion into Nanostructured δ-MnO 2 : A Nonaqueous Rechargeable Zn Metal Battery

    DOE PAGES

    Han, Sang-Don; Kim, Soojeong; Li, Dongguo; ...

    2017-05-08

    Unlike the more established lithium-ion based energy storage chemistries, the complex intercalation chemistry of multivalent cations in a host lattice is not well understood, especially the relationship between the intercalating species solution chemistry and the prevalence and type of side reactions. Among multivalent metals, a promising model system can be based on nonaqueous Zn 2+ ion chemistry. There are several examples of these systems support the use of a Zn metal anode, and reversible intercalation cathodes have been reported. Our study utilizes a combination of analytical tools to probe the chemistry of a nanostructured δ-MnO 2 cathode in association withmore » a nonaqueous acetonitrile–Zn(TFSI) 2 electrolyte and a Zn metal anode. As many of the issues related to understanding a multivalent battery relate to the electrolyte–electrode interface, the high surface area of a nanostructured cathode provides a significant interface between the electrolyte and cathode host that maximizes the spectroscopic signal of any side reactions or minor mechanistic pathways. There are numerous factors affecting capacity fade and issues associated with the second phase formation including Mn dissolution in heavily cycled Zn/δ-MnO 2 cells are presented including dramatic mechanistic differences in the storage mechanism of this couple when compared to similar aqueous electrolytes are noted.« less

  3. Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

    PubMed Central

    2016-01-01

    This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from “omics” studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments. PMID:27121074

  4. Key Scientific Issues in the Health Risk Assessment of Trichloroethylene

    PubMed Central

    Chiu, Weihsueh A.; Caldwell, Jane C.; Keshava, Nagalakshmi; Scott, Cheryl Siegel

    2006-01-01

    Trichloroethylene (TCE) is a common environmental contaminant at hazardous waste sites and in ambient and indoor air. Assessing the human health risks of TCE is challenging because of its inherently complex metabolism and toxicity and the widely varying perspectives on a number of critical scientific issues. Because of this complexity, the U.S. Environmental Protection Agency (EPA) drew upon scientific input and expertise from a wide range of groups and individuals in developing its 2001 draft health risk assessment of TCE. This scientific outreach, which was aimed at engaging a diversity of perspectives rather than developing consensus, culminated in 2000 with 16 state-of-the-science articles published together as an Environmental Health Perspectives supplement. Since that time, a substantial amount of new scientific research has been published that is relevant to assessing TCE health risks. Moreover, a number of difficult or controversial scientific issues remain unresolved and are the subject of a scientific consultation with the National Academy of Sciences coordinated by the White House Office of Science and Technology Policy and co-sponsored by a number of federal agencies, including the U.S. EPA. The articles included in this mini-monograph provide a scientific update on the most prominent of these issues: the pharmacokinetics of TCE and its metabolites, mode(s) of action and effects of TCE metabolites, the role of peroxisome proliferator–activated receptor in TCE toxicity, and TCE cancer epidemiology. PMID:16966103

  5. Issues impacting therapeutic outcomes in pediatric patients: an overview.

    PubMed

    Kalra, Atin; Goindi, Shishu

    2014-01-01

    The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

  6. Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems.

    PubMed

    Hallifax, D; Houston, J B

    2009-03-01

    Mechanistic prediction of unbound drug clearance from human hepatic microsomes and hepatocytes correlates with in vivo clearance but is both systematically low (10 - 20 % of in vivo clearance) and highly variable, based on detailed assessments of published studies. Metabolic capacity (Vmax) of commercially available human hepatic microsomes and cryopreserved hepatocytes is log-normally distributed within wide (30 - 150-fold) ranges; Km is also log-normally distributed and effectively independent of Vmax, implying considerable variability in intrinsic clearance. Despite wide overlap, average capacity is 2 - 20-fold (dependent on P450 enzyme) greater in microsomes than hepatocytes, when both are normalised (scaled to whole liver). The in vitro ranges contrast with relatively narrow ranges of clearance among clinical studies. The high in vitro variation probably reflects unresolved phenotypical variability among liver donors and practicalities in processing of human liver into in vitro systems. A significant contribution from the latter is supported by evidence of low reproducibility (several fold) of activity in cryopreserved hepatocytes and microsomes prepared from the same cells, between separate occasions of thawing of cells from the same liver. The large uncertainty which exists in human hepatic in vitro systems appears to dominate the overall uncertainty of in vitro-in vivo extrapolation, including uncertainties within scaling, modelling and drug dependent effects. As such, any notion of quantitative prediction of clearance appears severely challenged.

  7. The Contribution of z < or Approx. 6 Sources to the Spatial Coherence in the Unresolved Cosmic Near-Infrared and X-Ray Backgrounds

    NASA Technical Reports Server (NTRS)

    Helgason, K.; Cappelluti, N.; Hasinger, G.; Kashlinsky, A.; Ricotti, M.

    2014-01-01

    A spatial clustering signal has been established in Spitzer/IRAC measurements of the unresolved cosmic near-infrared background (CIB) out to large angular scales, approx. 1deg. This CIB signal, while significantly exceeding the contribution from the remaining known galaxies, was further found to be coherent at a highly statistically significant level with the unresolved soft cosmic X-ray background (CXB). This measurement probes the unresolved CXB to very faint source levels using deep near-IR source subtraction.We study contributions from extragalactic populations at low to intermediate redshifts to the measured positive cross-power signal of the CIB fluctuations with the CXB. We model the X-ray emission from active galactic nuclei (AGNs), normal galaxies, and hot gas residing in virialized structures, calculating their CXB contribution including their spatial coherence with all infrared emitting counterparts. We use a halo model framework to calculate the auto and cross-power spectra of the unresolved fluctuations based on the latest constraints of the halo occupation distribution and the biasing of AGNs, galaxies, and diffuse emission. At small angular scales (1), the 4.5microns versus 0.5-2 keV coherence can be explained by shot noise from galaxies and AGNs. However, at large angular scales (approx.10), we find that the net contribution from the modeled populations is only able to account for approx. 3% of the measured CIB×CXB cross-power. The discrepancy suggests that the CIB×CXB signal originates from the same unknown source population producing the CIB clustering signal out to approx. 1deg.

  8. [Attachment Representation and Emotion Regulation in Patients with Burnout Syndrome].

    PubMed

    Söllner, Wolfgang; Behringer, Johanna; Böhme, Stephanie; Stein, Barbara; Reiner, Iris; Spangler, Gottfried

    2016-06-01

    Burnout describes a syndrome of exhaustion resulting from insufficient coping with work-related distress. We investigated if patients that are being clinically treated for burnout show insecure and unresolved attachment representation more often compared with healthy controls. 50 out of 60 consecutive burnout patients participated in the study. Mental representation of attachment was measured by using the Adult Attachment Interview. Additionally, we administered the Self Report Questionnaire to Assess Emotional Experience and Emotion Regulation and several burnout specific questionnaires. A population sample was used as control group. Burnout patients were classified as insecurely attached significantly more often than controls. Unresolved attachment status concerning loss or trauma was found significantly more often within the burnout sample. Patients with insecure attachment representation reported a lower subjective significance of work. Patients with avoidant insecure attachment showed more depersonalisation. Patients with unresolved loss/trauma reported less social support. They showed more passive-negative emotion experience and emotion regulation characterized by externalization. The results of the study suggest that an insecure or unresolved attachment representation might constitute an intrapersonal risk factor for the development of burnout syndrome. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Treating Unresolved Grief and Posttraumatic Stress Symptoms in Orphaned Children in Tanzania: Group-based Trauma-focused Cognitive Behavioral Therapy

    PubMed Central

    O’Donnell, Karen; Dorsey, Shannon; Gong, Wenfeng; Ostermann, Jan; Whetten, Rachel; Cohen, Judith A.; Itemba, Dafrosa; Manongi, Rachel; Whetten, Kathryn

    2015-01-01

    The study was designed to test the feasibility and child clinical outcomes for a group-based application of Trauma-focused Cognitive Behavior Therapy (TF-CBT) for orphaned children with unresolved grief in Moshi, Tanzania. Sixty-four orphaned children with at least mild symptoms of unresolved grief and/or traumatic stress and their guardians participated in the open trial. The evidence-based TF-CBT protocol was adapted for group delivery, resulting in 12 weekly sessions for child and guardians separately with conjoint activities and three individual visits. Using a task-sharing approach, the intervention was delivered by lay counselors with no prior mental health experience. Primary outcomes assessed were symptoms of unresolved grief and posttraumatic stress (PTS); secondary outcomes included symptoms of depression and overall behavioral adjustment. All assessments were conducted pre-treatment, post-treatment, and 3- and 12-months after the end of treatment. Results showed improved scores on all outcomes post-treatment, sustained at 3 and 12 months. Effect sizes (Cohen’s d) for baseline to post-treatment were 1.36 for child reported grief symptoms; 1.87 for child-reported PTS, and 1.15 for caregiver report of child PTS. PMID:25418514

  10. Waiting for Brandon: How Readers Respond to Small Mysteries

    PubMed Central

    Gerrig, Richard J.; Love, Jessica; McKoon, Gail

    2009-01-01

    When readers experience narratives they often encounter small mysteries—questions that a text raises that are not immediately settled. In our experiments, participants read stories that introduced characters by proper names (e.g., “It’s just that Brandon hasn’t called in so long”). Resolved versions of the stories specified the functions those characters’ assumed in their narrative worlds with respect to the other characters (e.g., Brandon was identified as the speaker’s grandson); unresolved versions of the stories did not immediately provide that information. We predicted that characters whose functions were still unresolved would remain relatively accessible in the discourse representations. We tested that prediction in Experiments 1 and 2 by asking participants to indicate whether a name (e.g., Brandon) had appeared in the story. Participants responded most swiftly when the characters remained unresolved. In the latter experiments, we demonstrated that the presence of an unresolved character disrupted processing of information that followed that character’s introduction (Experiment 3) but not information that preceded that introduction (Experiment 4). These results support the general importance of providing a theoretical account of readers’ responses to narrative mysteries. PMID:20046984

  11. A sibling adoption study of adult attachment: The influence of shared environment on attachment states of mind

    PubMed Central

    Caspers, Kristin; Yucuis, Rebecca; Troutman, Beth; Arndt, Stephan; Langbehn, Douglas

    2009-01-01

    This study extends existing research investigating sibling concordance on attachment by examining concordance for adult attachment in a sample of 126 genetically unrelated sibling pairs. The Adult Attachment Interview (George, Kaplan, & Main, 1985; Main, Goldwyn, & Hesse, 2003) was used to assess states of mind with regard to attachment. The average age of the participants was 39 years old. The distribution of attachment classifications was independent of adoptive status. Attachment concordance rates were unassociated with gender concordance and sibling age difference. Concordance for autonomous/non-autonomous classifications was significant at 61% as was concordance for primary classifications at 53%. The concordance rate for not-unresolved/unresolved was non-significant at 67%. Our findings demonstrate similarity of working models of attachment between siblings independent of genetic relatedness between siblings and generations (i.e., parent and child). These findings extend previous research by further implicating shared environment as a major influence on sibling similarities on organized patterns of attachment in adulthood. The non-significant concordance for the unresolved classification suggests that unresolved loss or trauma may be less influenced by shared environment and more likely to be influenced by post-childhood experiences or genetic factors. PMID:18049934

  12. Investigating the physical and geometrical properties of the dusty torus in QSO

    NASA Astrophysics Data System (ADS)

    Martínez-Paredes, M.; González-Martín, O.; Aretxaga, I.; Alonso-Herrero, A.

    2017-07-01

    Usining mid-IR high angular resolution (0.3 arcsec) data from CanariCam on the 10.4m Gran Telescopio CANARIAS we study the mid-IR nuclear emission of a nearby (z<0.1) sample of QSOs. The QSOs are selected with N-band flux (fN>0.02 Jy) and hard X-ray flux (fX(2-10 keV)>1043 erg s-1). From the analysis of this data we find that the mid-IR emission is unresolved at scales of a few hundred of pc. We use unresolved emission at H-band (e.g., Veilleux et al. 2009b) and the IRS-Spitzer spectrum (e.g., Schweitzer et al. 2006) to build near- to mid-IR unresolved spectral energy distribution (SEDs).

  13. Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain

    PubMed Central

    Lee, Michael C.; Wanigasekera, Vishvarani; Tracey, Irene

    2014-01-01

    Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’. PMID:23891639

  14. Osimertinib for the treatment of non-small cell lung cancer.

    PubMed

    Sun, Jong-Mu; Lee, Se-Hoon; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju

    2017-02-01

    The T790 M mutation of the epidermal growth factor receptor (EGFR) gene is the most common mechanism underlying resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR TKI, shows robust clinical efficacy in patients with T790 M-mutated lung cancer. Areas covered: We analyzed and reviewed clinical data for which patients who experienced acquired resistance to first- or second-generation EGFR TKIs. In addition, we briefly reviewed the potential role of osimertinib as a first-line therapy. Expert opinion: Osimertinib was recently licensed for use in NSCLC patients with acquired resistance to other EGFR TKIs due to a T790 M mutation. However, unresolved issues surrounding the optimal application of osimertinib remain, specifically the development of a plasma-based mutation test to overcome the difficulty of repeat biopsy, the efficacy of osimertinib for brain or leptomeningeal metastases, the development of resistance to osimertinib, and the use of osimertinib therapy as a first-line treatment. Many ongoing studies are currently exploring these issues.

  15. Potential Impacts of Hydrokinetic and Wave Energy Conversion Technologies on Aquatic Environments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Čada, Glenn F.

    2007-04-01

    A new generation of hydropower technologies, the kinetic hydro and wave energy conversion devices, offers the possibility of generating electricity from the movements of water, without the need for dams and diversions. The Energy Policy Act of 2005 encouraged the development of these sources of renewable energy in the United States, and there is growing interest in deploying them globally. The technologies that would extract electricity from free-flowing streams, estuaries, and oceans have not been widely tested. Consequently, the U.S. Department of Energy convened a workshop to (1) identify the varieties of hydrokinetic energy and wave energy conversion devices andmore » their stages of development, (2) identify where these technologies can best operate, (3) identify the potential environmental issues associated with these technologies and possible mitigation measures, and (4) develop a list of research needs and/or practical solutions to address unresolved environmental issues. The article reviews the results of that workshop, focusing on potential effects on freshwater, estuarine, and marine ecosystems, and we describe recent national and international developments.« less

  16. Protecting indigenous rights. Guatemala.

    PubMed

    1996-01-01

    Guatemala's recent ratification of the International Labor Organization (ILO) Convention regarding indigenous and tribal peoples (1989, No. 169) represents a commitment to guarantee the rights of the country's majority Mayan population. Ratifying governments are obligated to respect the traditional values and land rights of tribal and indigenous peoples and to consult with them on any decisions affecting their economic or social development. Ratification of this Convention was a key element in an eight-part UN-sponsored negotiation aimed at ending the civil war in Guatemala. Efforts are underway to promote dialogue between organized civil society and government. Negotiations in May 1996, conducted with ILO assistance, resulted in a socioeconomic agreement under which Guatemala will increase social investment in education, undertake agrarian reform, and institute tripartite consultation on all major social and economic issues. However, two key issues in the peace negotiations--the role of the army in civil society and constitutional reform--remain unresolved. The final global peace accord is expected to be signed in September 1996. UN organizations are already working to mobilize international support for transforming these agreements into political and social realities for the Guatemalan people.

  17. First-time viewers' comprehension of films: bridging shot transitions.

    PubMed

    Ildirar, Sermin; Schwan, Stephan

    2015-02-01

    Which perceptual and cognitive prerequisites must be met in order to be able to comprehend a film is still unresolved and a controversial issue. In order to gain some insights into this issue, our field experiment investigates how first-time adult viewers extract and integrate meaningful information across film cuts. Three major types of commonalities between adjacent shots were differentiated, which may help first-time viewers with bridging the shots: pictorial, causal, and conceptual. Twenty first-time, 20 low-experienced and 20 high-experienced viewers from Turkey were shown a set of short film clips containing these three kinds of commonalities. Film clips conformed also to the principles of continuity editing. Analyses of viewers' spontaneous interpretations show that first-time viewers indeed are able to notice basic pictorial (object identity), causal (chains of activity), as well as conceptual (links between gaze direction and object attention) commonalities between shots due to their close relationship with everyday perception and cognition. However, first-time viewers' comprehension of the commonalities is to a large degree fragile, indicating the lack of a basic notion of what constitutes a film. © 2014 The British Psychological Society.

  18. Integration of Technology-based Behavioral Health Interventions in Substance Abuse and Addiction Services

    PubMed Central

    Ramsey, Alex

    2015-01-01

    The past decade has witnessed revolutionary changes to the delivery of health services, ushered in to a great extent by the introduction of electronic health record systems. More recently, a new class of technological advancements—technology-based behavioral health interventions, which involve the delivery of evidence-informed practices via computers, web-based applications, mobile phones, wearable sensors, or other technological platforms—has emerged and is primed to once again radically shift current models for behavioral healthcare. Despite the promise and potential of these new therapeutic approaches, a greater understanding of the impact of technology-based interventions on cornerstone issues of mental health and addiction services—namely access, quality, and cost—is needed. The current review highlights 1) relevant conceptual frameworks that guide this area of research, 2) key studies that inform the relevance of technology-based interventions for behavioral healthcare access, quality, and cost, 3) pressing methodological issues that require attention, 4) unresolved questions that warrant further investigation, and 5) practical implications that underscore important new directions for this emerging area of research. PMID:26161047

  19. Integration of Technology-based Behavioral Health Interventions in Substance Abuse and Addiction Services.

    PubMed

    Ramsey, Alex

    2015-08-01

    The past decade has witnessed revolutionary changes to the delivery of health services, ushered in to a great extent by the introduction of electronic health record systems. More recently, a new class of technological advancements-technology-based behavioral health interventions, which involve the delivery of evidence-informed practices via computers, web-based applications, mobile phones, wearable sensors, or other technological platforms-has emerged and is primed to once again radically shift current models for behavioral healthcare. Despite the promise and potential of these new therapeutic approaches, a greater understanding of the impact of technology-based interventions on cornerstone issues of mental health and addiction services-namely access, quality, and cost -is needed. The current review highlights 1) relevant conceptual frameworks that guide this area of research, 2) key studies that inform the relevance of technology-based interventions for behavioral healthcare access, quality, and cost, 3) pressing methodological issues that require attention, 4) unresolved questions that warrant further investigation, and 5) practical implications that underscore important new directions for this emerging area of research.

  20. Rule extraction from minimal neural networks for credit card screening.

    PubMed

    Setiono, Rudy; Baesens, Bart; Mues, Christophe

    2011-08-01

    While feedforward neural networks have been widely accepted as effective tools for solving classification problems, the issue of finding the best network architecture remains unresolved, particularly so in real-world problem settings. We address this issue in the context of credit card screening, where it is important to not only find a neural network with good predictive performance but also one that facilitates a clear explanation of how it produces its predictions. We show that minimal neural networks with as few as one hidden unit provide good predictive accuracy, while having the added advantage of making it easier to generate concise and comprehensible classification rules for the user. To further reduce model size, a novel approach is suggested in which network connections from the input units to this hidden unit are removed by a very straightaway pruning procedure. In terms of predictive accuracy, both the minimized neural networks and the rule sets generated from them are shown to compare favorably with other neural network based classifiers. The rules generated from the minimized neural networks are concise and thus easier to validate in a real-life setting.

  1. Development of Low Density Flexible Carbon Phenolic Ablators

    NASA Technical Reports Server (NTRS)

    Stackpole, Mairead; Thornton, Jeremy; Fan, Wendy; Agrawal, Parul; Doxtad, Evan; Gasch, Matt

    2011-01-01

    Phenolic Impregnated Carbon Ablator (PICA) was the enabling TPS material for the Stardust mission where it was used as a single piece heatshield. PICA has the advantages of low density (0.27g/cm3) coupled with efficient ablative capability at high heat fluxes. Under the Orion program, PICA was also shown to be capable of both ISS and lunar return missions however some unresolved issues remain for its application in a tiled configuration for the Orion-specific design. In particular, the problem of developing an appropriate gap filler resulted in the Orion program selecting AVCOAT as the primary heatshield material over PICA. We are currently looking at alternative architectures to yield flexible and more conformal carbon phenolic materials with comparable densities to PICA that will address some of the design issues faced in the application of a tiled PICA heat shield. These new materials are viable TPS candidates for upcoming NASA missions and as material candidates for private sector Commercial Orbital Transportation Services (COTS). This presentation will discuss flexible alternatives to PICA and include preliminary mechanical and thermal properties as well as arc jet and LHMEL screening test results.

  2. A Scopus-Based Analysis of Publication Activity in Kazakhstan from 2010 to 2015: Positive Trends, Concerns, and Possible Solutions.

    PubMed

    Yessirkepov, Marlen; Nurmashev, Bekaidar; Anartayeva, Mariya

    2015-12-01

    The article analyzes the publication activity of scientific authors from Kazakhstan based on Scopus and SCImago Journal & Country Rank data from 2010 to 2015. The number of indexed multidisciplinary and medical articles from the country has been steadily growing from 2011 onward and this can be due to the adoption of the new Law on Science in that year. Several regulatory legal acts have been issued in recent years aimed at improving the quality of local journals and the international recognition of academic degrees and titles. Publication activity of scientific authors from Kazakhstan was found to be higher than that from other countries in the Central Asian region. However, there are still many unresolved issues related to the English language barrier, lack of indexing status of local journals, and poor topical education on science writing and editing. As such, the number of articles published in 'predatory' journals remains sizable, and there are concerns over authors' negligence and plagiarism. The global solution to the discussed problems may be achieved by educating researchers, authors, reviewers, and editors.

  3. Tensions among siblings in parent care.

    PubMed

    Lashewicz, Bonnie; Keating, Norah

    2009-06-01

    From a place of "genealogical equivalence" as children of their parents, siblings spend a lifetime developing separate identities. As parents near the end of their lives, issues of sibling equivalence are renegotiated in the face of equal obligations to provide care and equal entitlement to parent assets. In this paper, we hypothesize how unresolved issues of rivalry for parent affection/attention among siblings may be reasserted when parents need care. Data are drawn from a project about how parent care and assets are shared. In-depth interviews with three sibling groups experiencing conflict over sharing parent care and assets along with six Canadian legal case portrayals of disputes among siblings over how parent care and assets were shared are examined. Findings are that disputes occur when siblings perceive others as dominating parent care and assets through tactics such as separating the parent from other siblings and preventing other siblings from being engaged in decisions about care and assets. Discussion is focused on paradoxes faced by siblings given expectations for equity in parent relationships alongside perceived pre-eminence in care and asset decisions.

  4. A Scopus-Based Analysis of Publication Activity in Kazakhstan from 2010 to 2015: Positive Trends, Concerns, and Possible Solutions

    PubMed Central

    Nurmashev, Bekaidar; Anartayeva, Mariya

    2015-01-01

    The article analyzes the publication activity of scientific authors from Kazakhstan based on Scopus and SCImago Journal & Country Rank data from 2010 to 2015. The number of indexed multidisciplinary and medical articles from the country has been steadily growing from 2011 onward and this can be due to the adoption of the new Law on Science in that year. Several regulatory legal acts have been issued in recent years aimed at improving the quality of local journals and the international recognition of academic degrees and titles. Publication activity of scientific authors from Kazakhstan was found to be higher than that from other countries in the Central Asian region. However, there are still many unresolved issues related to the English language barrier, lack of indexing status of local journals, and poor topical education on science writing and editing. As such, the number of articles published in 'predatory' journals remains sizable, and there are concerns over authors' negligence and plagiarism. The global solution to the discussed problems may be achieved by educating researchers, authors, reviewers, and editors. PMID:26713071

  5. Slamming: Recent Progress in the Evaluation of Impact Pressures

    NASA Astrophysics Data System (ADS)

    Dias, Frédéric; Ghidaglia, Jean-Michel

    2018-01-01

    Slamming, the violent impact between a liquid and solid, has been known to be important for a long time in the ship hydrodynamics community. More recently, applications ranging from the transport of liquefied natural gas (LNG) in LNG carriers to the harvesting of wave energy with oscillating wave surge converters have led to renewed interest in the topic. The main reason for this renewed interest is that the extreme impact pressures generated during slamming can affect the integrity of the structures involved. Slamming fluid mechanics is challenging to describe, as much from an experimental viewpoint as from a numerical viewpoint, because of the large span of spatial and temporal scales involved. Even the physical mechanisms of slamming are challenging: What physical phenomena must be included in slamming models? An important issue deals with the practical modeling of slamming: Are there any simple models available? Are numerical models viable? What are the consequences for the design of structures? This article describes the loading processes involved in slamming, offers state-of-the-art results, and highlights unresolved issues worthy of further research.

  6. Global Analysis, Interpretation and Modelling: An Earth Systems Modelling Program

    NASA Technical Reports Server (NTRS)

    Moore, Berrien, III; Sahagian, Dork

    1997-01-01

    The Goal of the GAIM is: To advance the study of the coupled dynamics of the Earth system using as tools both data and models; to develop a strategy for the rapid development, evaluation, and application of comprehensive prognostic models of the Global Biogeochemical Subsystem which could eventually be linked with models of the Physical-Climate Subsystem; to propose, promote, and facilitate experiments with existing models or by linking subcomponent models, especially those associated with IGBP Core Projects and with WCRP efforts. Such experiments would be focused upon resolving interface issues and questions associated with developing an understanding of the prognostic behavior of key processes; to clarify key scientific issues facing the development of Global Biogeochemical Models and the coupling of these models to General Circulation Models; to assist the Intergovernmental Panel on Climate Change (IPCC) process by conducting timely studies that focus upon elucidating important unresolved scientific issues associated with the changing biogeochemical cycles of the planet and upon the role of the biosphere in the physical-climate subsystem, particularly its role in the global hydrological cycle; and to advise the SC-IGBP on progress in developing comprehensive Global Biogeochemical Models and to maintain scientific liaison with the WCRP Steering Group on Global Climate Modelling.

  7. New perspectives on neuronal development via microfluidic environments

    PubMed Central

    Millet, Larry J.; Gillette, Martha U.

    2012-01-01

    Understanding the signals that guide neuronal development and direct formation of axons, dendrites, and synapses during wiring of the brain is a fundamental challenge of developmental neuroscience. Discovering how local signals shape developing neurons has been impeded by the inability of conventional culture methods to interrogate micro-environments of complex neuronal cytoarchitectures, where different sub-domains encounter distinct chemical, physical, and fluidic features. Micro-fabrication techniques are enabling the creation of micro-environments tailored to neuronal structures and sub-domains, with unprecedented access and control. The design, fabrication, and properties of microfluidic devices offer significant advantages for addressing unresolved issues of neuronal development. These high-resolution approaches are poised to contribute new insights into mechanisms for restoring neuronal function and connectivity compromised by injury, stress, and neurodegeneration. PMID:23031246

  8. Condensed matter physics of planets - Puzzles, progress and predictions

    NASA Technical Reports Server (NTRS)

    Stevenson, D. J.

    1984-01-01

    Attention is given to some of the major unresolved issues concerned with the physics of planetary interiors. The important advances in observations, and experimental and theoretical investigations are briefly reviewed, and some areas for further study are identified, including: the characteristics of atomic and electronic degrees of freedom at the high pressures and temperatures typical of a condensed planetary core; the behavior of water at megabar pressures; and the nature of the core-alloy in the earth and in the core mantle phase boundary. Consideration is also given to the behavior of carbon at high pressures and temperatures in the presence of oxygen and hydrogen; the behavior of the volatile ice assemblage in Titan at pressures of 2-40 kbar; and the electrical conductivities of matter under planetary core conditions.

  9. Evidence-based disease management: its role in cardiovascular risk reduction.

    PubMed

    Fanning, Etta L

    2004-01-01

    Cardiovascular disease remains the most pressing healthcare problem in the United States. Traditional risk factors--hypertension, obesity, and diabetes-are still unresolved issues; and new risk factors--pre-diabetes, insulin resistance, and pediatric and adolescent diabetes-have emerged. There is an urgent need to identify the risk factors for cardiovascular disease, and address risk reduction with disease management and treatment for each factor, based on qualitative and quantitative approaches for developing the evidence base for public health action. The objectives of this paper are to review (i) the burden of cardiovascular illness-morbidity, mortality, and cost; (ii) risk factors and the emerging epidemic of adolescent obesity; (iii) the challenges of attaining target endpoints; and (iv) the attributes of a successful programmatic healthcare initiative for potential impact on cardiovascular care and, eventually, public health.

  10. Ethics in American Health 1: Ethical Approaches to Health Policy

    PubMed Central

    2008-01-01

    I trace the evolution of ethical approaches to health policy in the United States and examine a number of critical unresolved issues pertaining to the current set of frameworks. Several themes emerge. First, fair procedures claim more attention than substantive and procedural principles. Second, in the case of public deliberation, more focus has been placed on factors such as procedural mechanisms than on understanding how individuals and groups value different aspects of health and agree on health-related decisions. Third, the nation needs workable frameworks to guide collective choices about valuable social ends and their trade-offs; purely procedural strategies are limited in illuminating overarching health policy and ethics questions. There is a need to integrate consequential and procedural approaches to health ethics and policy. PMID:18703449

  11. [Inheritance and innovation of traditional Chinese medicinal authentication].

    PubMed

    Zhao, Zhong-zhen; Chen, Hu-biao; Xiao, Pei-gen; Guo, Ping; Liang, Zhi-tao; Hung, Fanny; Wong, Lai-lai; Brand, Eric; Liu, Jing

    2015-09-01

    Chinese medicinal authentication is fundamental for the standardization and globalization of Chinese medicine. The discipline of authentication addresses difficult issues that have remained unresolved for thousands of years, and is essential for preserving safety. Chinese medicinal authentication has both scientific and traditional cultural connotations; the use of scientific methods to elucidate traditional experience-based differentiation carries the legacy of Chinese medicine forward, and offers immediate practical significance and long-term scientific value. In this paper, a path of inheritance and innovation is explored through the scientific exposition of Chinese medicinal authentication, featuring a review of specialized publications, the establishment of a Chinese medicine specimen center and Chinese medicinal image databases, the expansion of authentication technologies, and the formation of a cultural project dedicated to the Compedium of Materia Medica.

  12. Fistulizing Crohn’s disease: Diagnosis and management

    PubMed Central

    Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter

    2013-01-01

    Fistulizing Crohn’s disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn’s disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery. PMID:24917961

  13. Towards an internal model in pilot training.

    PubMed

    Braune, R J; Trollip, S R

    1982-10-01

    Optimal decision making requires an information seeking behavior which reflects the comprehension of the overall system dynamics. Research in the area of human monitors in man-machine systems supports the notion of an internal model with built-in expectancies. It is doubtful that the current approach to pilot training helps develop this internal model in the most efficient way. But this is crucial since the role of the pilot is changing to a systems' manager and decision maker. An extension of the behavioral framework of pilot training might help to prepare the pilot better for the increasingly complex flight environment. This extension is based on the theoretical model of schema theory, which evolved out of psychological research. The technological advances in aircraft simulators and in-flight performance measurement devices allow investigation of the still-unresolved issues.

  14. New measures of mental state and behavior based on data collected from sensors, smartphones, and the Internet.

    PubMed

    Glenn, Tasha; Monteith, Scott

    2014-12-01

    With the rapid and ubiquitous acceptance of new technologies, algorithms will be used to estimate new measures of mental state and behavior based on digital data. The algorithms will analyze data collected from sensors in smartphones and wearable technology, and data collected from Internet and smartphone usage and activities. In the future, new medical measures that assist with the screening, diagnosis, and monitoring of psychiatric disorders will be available despite unresolved reliability, usability, and privacy issues. At the same time, similar non-medical commercial measures of mental state are being developed primarily for targeted advertising. There are societal and ethical implications related to the use of these measures of mental state and behavior for both medical and non-medical purposes.

  15. Regulation of Body Temperature by the Nervous System.

    PubMed

    Tan, Chan Lek; Knight, Zachary A

    2018-04-04

    The regulation of body temperature is one of the most critical functions of the nervous system. Here we review our current understanding of thermoregulation in mammals. We outline the molecules and cells that measure body temperature in the periphery, the neural pathways that communicate this information to the brain, and the central circuits that coordinate the homeostatic response. We also discuss some of the key unresolved issues in this field, including the following: the role of temperature sensing in the brain, the molecular identity of the warm sensor, the central representation of the labeled line for cold, and the neural substrates of thermoregulatory behavior. We suggest that approaches for molecularly defined circuit analysis will provide new insight into these topics in the near future. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Protecting the Rights of School Children with Diabetes

    PubMed Central

    Wood, James M.

    2013-01-01

    School children with diabetes are facing increasing difficulties in receiving care during the school day. Despite theexistence of federal statutes ensuring their rights to a free, appropriate public education, many school districts throughout the country do little, if anything, to ensure that their condition is treated throughout the school day. The chronic shortage of school nurses has resulted in hardships on families, relatives, and friends to ensure that care, including insulin, is timely and appropriately provided. While many states have taken measures to provide care by unlicensed trained volunteers, efforts to accomplish this in California have resulted in prolonged litigation. A variety of nursing organizations oppose all efforts to train unlicensed volunteers, arguing that such is not permitted by California law. The issue is unresolved and currently pending in the California Supreme Court. PMID:23566990

  17. “Cleansing” anatomical collections: The politics of removing specimens from German anatomical and medical collections 1988–92

    PubMed Central

    Weindling, Paul

    2015-01-01

    SUMMARY In 1989–90 an intense debate erupted in the Federal Republic of Germany over the status of anatomical specimens from the period of National Socialism. Pressure was brought on the German universities and research institutes to remove body parts. The solution was deemed rapid burial of all specimens whose provenance was in doubt. A range of options was considered, and the eventual decision to bury cremated remains was deemed the best way to draw a line under an uncomfortable past of Nazi medical atrocities. The aim was to achieve closure on this issue by a rapid “cleansing” of collections. However, identification of victims was left unresolved amidst the heated debates at the time. PMID:22445542

  18. Successful Treatment of Treatment-Resistant Schizophrenia in a 10-Year-Catatonic Patient by Augmentation of Selective Serotonin Reuptake Inhibitors

    PubMed Central

    Chen, Mei-Jung; Huang, Shiau-Shian; Juang, Kai-Dih; Chan, Chin-Hong

    2015-01-01

    Abstract Although catatonia is a well defined syndrome, the treatment of chronic catatonia remains an unresolved issue. Here, we report a successful treatment of a 30-year-old patient with treatment-resistant catatonic schizophrenia in 10 years by augmentation of selective serotonin reuptake inhibitors (SSRIs). We present a 30-year-old man with treatment-resistant catatonic schizophrenia who failed to respond to the treatment of benzodiazepines and antipsychotics for 10 years. He markedly improved after taking SSRIs. Now, he does not hold odd postures and begins to talk and show more facial expressions. We postulate that the therapeutic effect is related to the enhancement of 5-HT neurotransmission. SSRIs can be a considerable choice to treat chronic catatonia. PMID:25929916

  19. Successful treatment of treatment-resistant schizophrenia in a 10-year-catatonic patient by augmentation of selective serotonin reuptake inhibitors: a case report.

    PubMed

    Chen, Mei-Jung; Huang, Shiau-Shian; Juang, Kai-Dih; Chan, Chin-Hong

    2015-05-01

    Although catatonia is a well defined syndrome, the treatment of chronic catatonia remains an unresolved issue. Here, we report a successful treatment of a 30-year-old patient with treatment-resistant catatonic schizophrenia in 10 years by augmentation of selective serotonin reuptake inhibitors (SSRIs).We present a 30-year-old man with treatment-resistant catatonic schizophrenia who failed to respond to the treatment of benzodiazepines and antipsychotics for 10 years. He markedly improved after taking SSRIs. Now, he does not hold odd postures and begins to talk and show more facial expressions.We postulate that the therapeutic effect is related to the enhancement of 5-HT neurotransmission. SSRIs can be a considerable choice to treat chronic catatonia.

  20. The Concept of “Metaemotion”: What is There to Learn From Research on Metacognition?

    PubMed Central

    Norman, Elisabeth; Furnes, Bjarte

    2014-01-01

    We first present a selection of vignette examples from empirical psychological research to illustrate how the phenomenon of metaemotion (Gottman, Katz, & Hooven, 1996; Mendonça, 2013) is studied within different domains of psychology. We then present a theoretical distinction which has been made between three facets of metacognition, namely metacognitive experiences, metacognitive knowledge, and metacognitive strategies (e.g., Efklides, 2008; Flavell, 1979). Referring back to the vignette examples from metaemotion research, we argue that a similar distinction can be drawn between three facets of metaemotion, namely metaemotional experiences, metaemotional knowledge, and metaemotional strategies. We argue that this distinction clarifies some of the unresolved issues in metaemotion research, and therefore has important implications for the study of metaemotion, both methodologically and theoretically. PMID:27110281

  1. A foundation for public health ethics at Tuskegee University in the 21st century.

    PubMed

    Warren, Rueben C; Tarver, Will L

    2010-08-01

    This commentary is a reflection on Tuskegee University's National Center for Bioethics in Research and Health Care on the health and ethical challenges of the 21st century. The Center has dedicated the last 10 years to addressing the unresolved biomedicine and public health issues and/or the ethical dilemmas that plague the nation's health. The authors believe that health disparities continue to worsen because the approach under-appreciates the ethical dilemma that plagues health policy and health disparities. The authors discuss synergies and the paradigmatic differences between science and medicine, religion, spirituality, and faith. They also discuss the importance of considering these relationships if improvements in the health of people of African descent are expected. The concept of Optimal Health is explored.

  2. Individual Differences, Intelligence, and Behavior Analysis

    PubMed Central

    Williams, Ben; Myerson, Joel; Hale, Sandra

    2008-01-01

    Despite its avowed goal of understanding individual behavior, the field of behavior analysis has largely ignored the determinants of consistent differences in level of performance among individuals. The present article discusses major findings in the study of individual differences in intelligence from the conceptual framework of a functional analysis of behavior. In addition to general intelligence, we discuss three other major aspects of behavior in which individuals differ: speed of processing, working memory, and the learning of three-term contingencies. Despite recent progress in our understanding of the relations among these aspects of behavior, numerous issues remain unresolved. Researchers need to determine which learning tasks predict individual differences in intelligence and which do not, and then identify the specific characteristics of these tasks that make such prediction possible. PMID:18831127

  3. Flame spread across liquids

    NASA Technical Reports Server (NTRS)

    Ross, Howard D.; Miller, Fletcher; Schiller, David; Sirignano, William

    1995-01-01

    Recent reviews of our understanding of flame spread across liquids show that there are many unresolved issues regarding the phenomenology and causal mechanisms affecting ignition susceptibility, flame spread characteristics, and flame spread rates. One area of discrepancy is the effect of buoyancy in both the uniform and pulsating spread regimes. The approach we have taken to resolving the importance of buoyancy for these flames is: (1) normal gravity (1g) and microgravity (micro g) experiments; and (2) numerical modeling at different gravitational levels. Of special interest to this work, as discussed at the previous workshop, is the determination of whether, and under what conditions, pulsating spread occurs in micro g. Microgravity offers a unique ability to modify and control the gas-phase flow pattern by utilizing a forced air flow over the pool surface.

  4. Investigating the role of future thinking in social problem solving.

    PubMed

    Noreen, Saima; Whyte, Katherine E; Dritschel, Barbara

    2015-03-01

    There is well-established evidence that both rumination and depressed mood negatively impact the ability to solve social problems. A preliminary stage of the social problem solving process may be the process of catapulting oneself forward in time to think about the consequences of a problem before attempting to solve it. The aim of the present study was to examine how thinking about the consequences of a social problem being resolved or unresolved prior to solving it influences the solution of the problem as a function of levels of rumination and dysphoric mood. Eighty six participants initially completed the Beck Depression Inventory- II (BDI-II) and the Ruminative Response Scale (RRS). They were then presented with six social problems and generated consequences for half of the problems being resolved and half of the problems remaining unresolved. Participants then solved some of the problems, and following a delay, were asked to recall all of the consequences previously generated. Participants reporting higher levels of depressed mood and rumination were less effective at generating problem solutions. Specifically, those reporting higher levels of rumination produced less effective solutions for social problems that they had previously generated unresolved than resolved consequences. We also found that individuals higher in rumination, irrespective of depressed mood recalled more of the unresolved consequences in a subsequent memory test. As participants did not solve problems for scenarios where no consequences were generated, no baseline measure of problem solving was obtained. Our results suggest thinking about the consequences of a problem remaining unresolved may impair the generation of effective solutions in individuals with higher levels of rumination. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Combination of binaural and harmonic masking release effects in the detection of a single component in complex tones.

    PubMed

    Klein-Hennig, Martin; Dietz, Mathias; Hohmann, Volker

    2018-03-01

    Both harmonic and binaural signal properties are relevant for auditory processing. To investigate how these cues combine in the auditory system, detection thresholds for an 800-Hz tone masked by a diotic (i.e., identical between the ears) harmonic complex tone were measured in six normal-hearing subjects. The target tone was presented either diotically or with an interaural phase difference (IPD) of 180° and in either harmonic or "mistuned" relationship to the diotic masker. Three different maskers were used, a resolved and an unresolved complex tone (fundamental frequency: 160 and 40 Hz) with four components below and above the target frequency and a broadband unresolved complex tone with 12 additional components. The target IPD provided release from masking in most masker conditions, whereas mistuning led to a significant release from masking only in the diotic conditions with the resolved and the narrowband unresolved maskers. A significant effect of mistuning was neither found in the diotic condition with the wideband unresolved masker nor in any of the dichotic conditions. An auditory model with a single analysis frequency band and different binaural processing schemes was employed to predict the data of the unresolved masker conditions. Sensitivity to modulation cues was achieved by including an auditory-motivated modulation filter in the processing pathway. The predictions of the diotic data were in line with the experimental results and literature data in the narrowband condition, but not in the broadband condition, suggesting that across-frequency processing is involved in processing modulation information. The experimental and model results in the dichotic conditions show that the binaural processor cannot exploit modulation information in binaurally unmasked conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Partially-Averaged Navier Stokes Model for Turbulence: Implementation and Validation

    NASA Technical Reports Server (NTRS)

    Girimaji, Sharath S.; Abdol-Hamid, Khaled S.

    2005-01-01

    Partially-averaged Navier Stokes (PANS) is a suite of turbulence closure models of various modeled-to-resolved scale ratios ranging from Reynolds-averaged Navier Stokes (RANS) to Navier-Stokes (direct numerical simulations). The objective of PANS, like hybrid models, is to resolve large scale structures at reasonable computational expense. The modeled-to-resolved scale ratio or the level of physical resolution in PANS is quantified by two parameters: the unresolved-to-total ratios of kinetic energy (f(sub k)) and dissipation (f(sub epsilon)). The unresolved-scale stress is modeled with the Boussinesq approximation and modeled transport equations are solved for the unresolved kinetic energy and dissipation. In this paper, we first present a brief discussion of the PANS philosophy followed by a description of the implementation procedure and finally perform preliminary evaluation in benchmark problems.

  7. Special issue: Volcanic geology of the Azores Islands

    USGS Publications Warehouse

    Nunes, João Carlos; Tilling, Robert I.; Sigvaldason, Gudmundur E.

    2006-01-01

    The volcanic islands making up the Azores Archipelago rise above sea from a prominent submarine topographic high (the “Azores Plateau”), marked by the 2000-m bathymetric contour. Specifically, the Azores Islands lie at the so-called “Azores Triple Junction” (ATJ), where the Eurasian, North American, and African (or Nubian) tectonic plates meet. In general terms, the ATJ is defined by the Mid-Atlantic Ridge (MAR) separating the North American plate from the other two, and the Azores–Gibraltar fault zone separating the Eurasian and African plates. In addition, the existence of a mantle plume (“hotspot) beneath Azores Plateau has been inferred in many previous investigations. Not surprisingly, because of its distinctive plate-tectonics setting and attributes, the Azores Archipelago has been the site of intense research, serving as an ideal natural laboratory for scientific studies involving diverse disciplines, including geology, seismotectonics, climatology, ecology, and oceanography. Of course, a special field of interest and research is volcanology, with particular emphasis not only on the eruptive processes and products of the individual island volcanoes, but also of the volcanic and structural evolution of the ATJ and the “Azores Plateau” as a whole.There has been, and remains, considerable scientific debate about the dynamics of the ATJ, including the characterization of the nature and location of the involved plate boundaries, the determination of the sense and amount of plate motions, and the influence of the Azores hotspot on the involved three plates. At present, the basic nature of the ATJ is still not fully understood and the main unresolved issues are: where is the westernmost extent of Azores–Gibraltar fault zone? What is the nature of that extent? Is this fault zone a single, narrowly constricted linear boundary, or does it behave as a much larger, complex tectonic block (i.e., a “miniplate“ or “microplate”)? What is the size and location of the “Azores hot spot”? Is it fixed or moving?By way of background, with the aim of addressing at least the volcanological aspects of these unresolved scientific questions, a “Pico Island International Volcanological Meeting” has been convened three times in recent years (2001, 2002, and 2004). We originally were invited by Elsevier to produce a Special Issue of JVGR focusing on the main conclusions of the papers to be presented at 2002 Pico meeting. However, at the time, we believed that it would be more appropriate to have a Special Issue that would be broader in scope than the meeting itself and involve a greater number of potential contributors, by inviting all researchers in Portugal and abroad who have conducted geoscience studies in the Azores. Thus, this Special Issue contains contributions of those researchers who accepted our invitation to share with the global volcanologic community the findings and insights from their investigations of the Azores Islands and surrounding seafloor. The collection of papers in this Special Issue constitutes a representative sampling of the wide-ranging research conducted on the Azores Archipelago, on land and offshore. This sampling encompasses a variety of geological, geophysical, tomographical, petrologic–geochemical, geothermal studies, as well as assessments of natural hazards.

  8. On the possibility of a place code for the low pitch of high-frequency complex tonesa

    PubMed Central

    Santurette, Sébastien; Dau, Torsten; Oxenham, Andrew J.

    2012-01-01

    Harmonics are considered unresolved when they interact with neighboring harmonics and cannot be heard out separately. Several studies have suggested that the pitch derived from unresolved harmonics is coded via temporal fine-structure cues emerging from their peripheral interactions. Such conclusions rely on the assumption that the components of complex tones with harmonic ranks down to at least 9 were indeed unresolved. The present study tested this assumption via three different measures: (1) the effects of relative component phase on pitch matches, (2) the effects of dichotic presentation on pitch matches, and (3) listeners' ability to hear out the individual components. No effects of relative component phase or dichotic presentation on pitch matches were found in the tested conditions. Large individual differences were found in listeners' ability to hear out individual components. Overall, the results are consistent with the coding of individual harmonic frequencies, based on the tonotopic activity pattern or phase locking to individual harmonics, rather than with temporal coding of single-channel interactions. However, they are also consistent with more general temporal theories of pitch involving the across-channel summation of information from resolved and/or unresolved harmonics. Simulations of auditory-nerve responses to the stimuli suggest potential benefits to a spatiotemporal mechanism. PMID:23231119

  9. Labeling of trans fatty acid content in food, regulations and limits-the FDA view.

    PubMed

    Moss, Julie

    2006-05-01

    With the scientific evidence associating trans fatty acid (TFA) intake with an increased risk of coronary heart disease (CHD), the U.S. Food and Drug Administration (FDA) issued a final rule that requires the declaration of the amount of TFA present in foods, including dietary supplements, on the nutrition label by January 1, 2006. The addition of TFA to the nutrition label will lead to the prevention of 600 to 1200 cases of CHD and 240-480 deaths each year saving Dollars 900 million to Dollars 1.8 billion per year in medical costs, lost productivity, and pain and suffering. For the purpose of nutrition labeling, TFA are defined as the sum of all unsaturated fatty acids that contain one or more isolated (i.e. non-conjugated) double bonds in a trans configuration. There are many issues that FDA has yet to resolve: (1) defining nutrient content claims for "free" and "reduced" levels of trans fat, (2) placing limits on the amount of TFA in conjunction with saturated fat limits for nutrient content claims, health claims, and disclosure and disqualifying levels, (3) a daily value, and (4) a possible footnote or disclosure statement to enhance consumer understanding of cholesterol raising lipids. FDA issued an Advanced Notice of Proposed Rulemaking (ANPR) requesting comments on the unresolved issues. FDA will also be conducting consumer research to determine consumer understanding of various TFA labeling possibilities. Comments to the ANPR, results of consumer research and current science will be used by FDA to resolve these issues and to determine future rulemaking for TFA labeling.

  10. The Cost Effectiveness of Lubiprostone in Chronic Idiopathic Constipation.

    PubMed

    Pennington, Becky; Marriott, Emily-Ruth; Lichtlen, Peter; Akbar, Ayesha; Hatswell, Anthony J

    2018-01-04

    The objective of this study was to evaluate the cost effectiveness of lubiprostone, prucalopride, placebo and immediate referral to secondary care in chronic idiopathic constipation (CIC) in an economic model that was used by the UK National Institute for Health and Care Excellence (NICE) in developing guidance. We developed a cohort state-transition model to reflect the treatment pathway in CIC from the UK NHS and personal social services perspective. Time on treatment was determined by a treatment continuation rule using data from an indirect comparison and survival curves fitted to long-term data. Quality of life was defined by whether CIC was resolved or unresolved, using published values. Costs were determined by drug acquisition costs, invasive procedures and healthcare resource use (associated with resolved or unresolved CIC), using published UK sources. Deterministic and probabilistic sensitivity analyses were conducted. Over a 10-year time horizon, lubiprostone was more costly and more effective than placebo and immediate referral to secondary care, with incremental cost-effectiveness ratios (ICERs) of £58,979 and £21,152. Lubiprostone dominated prucalopride in the base case and with a time horizon of 1 year. The main sensitivity for the comparison against placebo was the assumptions around placebo cost and efficacy. The main sensitivity for the comparison against prucalopride was the endpoint used in the indirect comparison. Lubiprostone may be cost effective compared with prucalopride or immediate referral but not compared with placebo in the base case. The implementation of the guidance issued by NICE should increase quality of life for patients with CIC and provide a further treatment option.

  11. Use of the Adult Attachment Projective Picture System in the formulation of a case of an adolescent refugee with PTSD.

    PubMed

    Gander, Manuela; Diamond, Diana; Buchheim, Anna; Sevecke, Kathrin

    2018-03-16

    Forced displacements and their psychosocial consequences in adolescent refugees and their families have received increasing attention in recent years. Although supportive family relations play a key role in buffering the impact of traumatization in adolescents, parental ability to provide such is often subject to extreme pressure. Under conditions of forced dislocation and fear, maladaptive interpersonal strategies in the parent-child relationships may develop, contributing to the onset of psychopathology. We explore new aspects of attachment-related issues for the understanding and treatment of adolescent refugees who have experienced multiple traumas in their childhood. We used a multimethod assessment battery including the Adult Attachment Projective Picture System (AAP), the Structured Clinical Interview, the Youth Self Report and the Wechsler Intelligence Scale in an adolescent boy with post-traumatic stress disorder (PTSD). Our subject was an adolescent refugee from the Middle East who demonstrated an unresolved attachment when confronted with loss and fear. His responses on the AAP evoked aspects of insecure-unresolved attachment, including his belief that it is not safe to trust in attachment figures, his limited access to traumatic attachment experiences, his impaired ability to take concrete actions when dealing with threatening attachment situations and the unintentional role-reversal shed new light on our understanding of his traumatic experiences, family functioning and psychopathological symptoms. Our results demonstrate the utility of the AAP in an adolescent refugee with PTSD by expanding our knowledge of a diverse range of experiences across the interpersonal, cognitive, cultural and developmental contexts that formed the basis for an individualized treatment plan.

  12. Corallite skeletal morphological variation in Hawaiian Porites lobata

    NASA Astrophysics Data System (ADS)

    Tisthammer, Kaho H.; Richmond, Robert H.

    2018-06-01

    Due to their high morphological plasticity and complex evolutionary history, the species boundaries of many reef-building corals are poorly understood. The skeletal structures of corals have traditionally been used for species identification, but these structures can be highly variable, and currently we lack knowledge regarding the extent of morphological variation within species. Porites species are notorious for their taxonomic difficulties, both morphologically and genetically, and currently there are several unresolved species complexes in the Pacific. Despite its ubiquitous presence and broad use in coral research, Porites lobata belongs to one such unresolved species complex. To understand the degree of intraspecific variation in skeletal morphology, 120 corallites from the Hawaiian P. lobata were examined. A subset of samples from two genetically differentiated populations from contrasting high- and low-stress environments in Maunalua Bay, Hawaii, were then quantitatively analyzed using multivariate morphometrics. Our observations revealed high intraspecific variation in corallite morphology, as well as significant morphological differences between the two populations of P. lobata. Additionally, significant correlation was found between the morphological and genetic distances calculated from approximately 18,000 loci generated from restriction site-associated DNA sequencing. The unique morphological characters observed from the genetically differentiated population under environmental stress suggest that these characters may have adaptive values, but how such traits relate to fitness and how much plasticity they can exhibit remain to be determined by future studies. Relatively simple morphometric analyses used in our study can be useful in clarifying the existing ambiguity in skeletal architecture, thus contributing to resolving species issues in corals.

  13. Natural history of Homo erectus.

    PubMed

    Antón, Susan C

    2003-01-01

    Our view of H. erectus is vastly different today than when Pithecanthropus erectus was described in 1894. Since its synonimization into Homo, views of the species and its distribution have varied from a single, widely dispersed, polytypic species ultimately ancestral to all later Homo, to a derived, regional isolate ultimately marginal to later hominin evolution. A revised chronostratigraphic framework and recent work bearing either directly or indirectly on reconstructions of life-history patterns are reviewed here and, together with a review of the cranial and postcranial anatomy of H. erectus, are used to generate a natural history of the species. Here I argue that H. erectus is a hominin, notable for its increased body size, that originates in the latest Pliocene/earliest Pleistocene of Africa and quickly disperses into Western and Eastern Asia. It is also an increasingly derived hominin with several regional morphs sustained by intermittent isolation, particularly in Southeast Asia. This view differs from several current views, most especially that which recognizes only a single hominin species in the Pleistocene, H. sapiens, and those which would atomize H. erectus into a multiplicity of taxa. Following Jolly ([2001] Yrbk Phys Anthropol 44:177-204), the regional morphs of H. erectus may be productively viewed as geographically replacing allotaxa, rather than as the focus of unresolvable species debates. Such a view allows us to focus on the adaptations and biology of local groups, including questions of biogeographic isolation and local adaptation. A number of issues remain unresolved, including the significance of diversity in size and shape in the early African and Georgian records. Copyright 2003 Wiley-Liss, Inc.

  14. Independent Orbiter Assessment (IOA): FMEA/CIL assessment

    NASA Technical Reports Server (NTRS)

    Hinsdale, L. W.; Swain, L. J.; Barnes, J. E.

    1988-01-01

    The McDonnell Douglas Astronautics Company (MDAC) was selected to perform an Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL). Direction was given by the Orbiter and GFE Projects Office to perform the hardware analysis and assessment using the instructions and ground rules defined in NSTS 22206. The IOA analysis featured a top-down approach to determine hardware failure modes, criticality, and potential critical items. To preserve independence, the analysis was accomplished without reliance upon the results contained within the NASA and Prime Contractor FMEA/CIL documentation. The assessment process compared the independently derived failure modes and criticality assignments to the proposed NASA post 51-L FMEA/CIL documentation. When possible, assessment issues were discussed and resolved with the NASA subsystem managers. Unresolved issues were elevated to the Orbiter and GFE Projects Office manager, Configuration Control Board (CCB), or Program Requirements Control Board (PRCB) for further resolution. The most important Orbiter assessment finding was the previously unknown stuck autopilot push-button criticality 1/1 failure mode. The worst case effect could cause loss of crew/vehicle when the microwave landing system is not active. It is concluded that NASA and Prime Contractor Post 51-L FMEA/CIL documentation assessed by IOA is believed to be technically accurate and complete. All CIL issues were resolved. No FMEA issues remain that have safety implications. Consideration should be given, however, to upgrading NSTS 22206 with definitive ground rules which more clearly spell out the limits of redundancy.

  15. Reflecting on ethical and legal issues in wildlife disease.

    PubMed

    McCallum, Hamish; Hocking, Barbara Ann

    2005-08-01

    Disease in wildlife raises a number of issues that have not been widely considered in the bioethical literature. However, wildlife disease has major implications for human welfare. The majority of emerging human infectious diseases are zoonotic: this is, they occur in humans by cross-species transmissions from animal hosts. Managing these diseases often involves balancing concerns with human health against animal welfare and conservation concerns. Many infectious diseases of domestic animals are shared with wild animals, although it is often unclear whether the infection spills over from wild animals to domestic animals or vice versa. Culling is the standard means of managing such diseases, bringing economic considerations, animal welfare and conservation into conflict. Infectious diseases are also major threatening processes in conservation biology and their appropriate management by culling, vaccination or treatment raises substantial animal ethics issues. One particular issue of great significance in Australia is an ongoing research program to develop genetically modified pathogens to control vertebrate pests including rabbits, foxes and house mice. Release of any self-replicating GMO vertebrate pathogen gives rise to a whole series of ethical questions. We briefly review current Australian legal responses to these problems. Finally, we present two unresolved problems of general importance that are exemplified by wildlife disease. First, to what extent can or should 'bioethics' be broadened beyond direct concerns with human welfare to animal welfare and environmental welfare? Second, how should the irreducible uncertainty of ecological systems be accounted for in ethical decision making?

  16. Research on the cognitively impaired: lessons and warnings from the emergency research debate.

    PubMed

    Karlawish, J H; Sachs, G A

    1997-04-01

    To demonstrate that the recent events in emergency research have broad implications for the conduct of human subjects research with the cognitively impaired. This essay illustrates the similarities between the two kinds of research and suggests how understanding these similarities might help to resolve issues in human subjects research on the cognitively impaired. A review of pertinent journal articles, books, regulations, and court cases. The emergency research controversy resulted in large part because of conflicting interpretations of arguably inadequate research regulations. The proposed Food and Drug Administration (FDA) regulations include advance informed consent, a broad role for family in approving a subject's participation, replacement of a threshold of permissible risk, called minimal risk, with a more sensible balancing of risks and benefits, and a role for the community in research approval. The current state of research on the cognitively impaired suggests that many of the same problems exist now that existed in emergency research before the FDA issued its proposed regulations. The ongoing case of T.D. et al. vs N.Y. State Office of Mental Health suggest that unless steps are taken similar to those taken in emergency research, much of clinical research on the cognitively impaired could cease. Representatives of the government, medicine, and the public must recognize the unresolved issues and inadequate regulations relating to research on the cognitively impaired. The proposed FDA regulations for emergency research may provide guidance for a settlement of these issues.

  17. Ionizing Radiation: The issue of radiation quality

    NASA Astrophysics Data System (ADS)

    Prise, Kevin; Schettino, Giuseppe

    Types of Ionising radiations are differentiated from each other by fundamental characteristics of their energy deposition patterns when they interact with biological materials. At the level of the DNA these non-random patterns drive differences in the yields and distributions of DNA damage patterns and specifically the production of clustered damage or complex lesions. The complex radiation fields found in space bring significant challenges for developing a mechanistic understanding of radiation effects from the perspective of radiation quality as these consist of a diverse range of particle and energy types unique to the space environment. Linear energy transfer, energy deposited per unit track length in units of keV per micron, has long been used as a comparator for different types of radiation but has limitations in that it is an average value. Difference in primary core ionizations relative to secondary delta ray ranges vary significantly with particle mass and energy leading to complex interrelationships with damage production at the cellular level. At the cellular level a greater mechanistic understanding is necessary, linking energy deposition patterns to DNA damage patterns and cellular response, to build appropriate biophysical models that are predictive for different radiation qualities and mixed field exposures. Defined studies using monoenergetic beams delivered under controlled conditions are building quantitative data sets of both initial and long term changes in cells as a basis for a great mechanistic understanding of radiation quality effects of relevance to not only space exposures but clinical application of ion-beams.

  18. Binary Systems and the Initial Mass Function

    NASA Astrophysics Data System (ADS)

    Malkov, O. Yu.

    2017-07-01

    In the present paper we discuss advantages and disadvantages of binary stars, which are important for star formation history determination. We show that to make definite conclusions of the initial mass function shape, it is necessary to study binary population well enough to correct the luminosity function for unresolved binaries; to construct the mass-luminosity relation based on wide binaries data, and to separate observational mass functions of primaries, of secondaries, and of unresolved binaries.

  19. Distinguishing dark matter from unresolved point sources in the Inner Galaxy with photon statistics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Samuel K.; Lisanti, Mariangela; Safdi, Benjamin R., E-mail: samuelkl@princeton.edu, E-mail: mlisanti@princeton.edu, E-mail: bsafdi@princeton.edu

    2015-05-01

    Data from the Fermi Large Area Telescope suggests that there is an extended excess of GeV gamma-ray photons in the Inner Galaxy. Identifying potential astrophysical sources that contribute to this excess is an important step in verifying whether the signal originates from annihilating dark matter. In this paper, we focus on the potential contribution of unresolved point sources, such as millisecond pulsars (MSPs). We propose that the statistics of the photons—in particular, the flux probability density function (PDF) of the photon counts below the point-source detection threshold—can potentially distinguish between the dark-matter and point-source interpretations. We calculate the flux PDFmore » via the method of generating functions for these two models of the excess. Working in the framework of Bayesian model comparison, we then demonstrate that the flux PDF can potentially provide evidence for an unresolved MSP-like point-source population.« less

  20. Unresolved Galaxy Classifier for ESA/Gaia mission: Support Vector Machines approach

    NASA Astrophysics Data System (ADS)

    Bellas-Velidis, Ioannis; Kontizas, Mary; Dapergolas, Anastasios; Livanou, Evdokia; Kontizas, Evangelos; Karampelas, Antonios

    A software package Unresolved Galaxy Classifier (UGC) is being developed for the ground-based pipeline of ESA's Gaia mission. It aims to provide an automated taxonomic classification and specific parameters estimation analyzing Gaia BP/RP instrument low-dispersion spectra of unresolved galaxies. The UGC algorithm is based on a supervised learning technique, the Support Vector Machines (SVM). The software is implemented in Java as two separate modules. An offline learning module provides functions for SVM-models training. Once trained, the set of models can be repeatedly applied to unknown galaxy spectra by the pipeline's application module. A library of galaxy models synthetic spectra, simulated for the BP/RP instrument, is used to train and test the modules. Science tests show a very good classification performance of UGC and relatively good regression performance, except for some of the parameters. Possible approaches to improve the performance are discussed.

  1. Radio supernovae and super star clusters in the circumnuclear region of NGC 1365

    NASA Astrophysics Data System (ADS)

    Lindblad, P. O.; Kristen, H.

    Groundbased optical and VLA observations have shown that the nucleus of the barred Seyfert 1 galaxy NGC 1365 is surrounded by a number of star forming regions, or "hot spots", as well as a number of resolved and unresolved continuum radio sources. HST/FOC observations reveal that the nucleus is surrounded by a ring of very compact unresolved sources of the kind that have been discovered in a number of other galaxies, and that have been assumed to be very compact young globular star clusters. The hot spots are resolved into groups of such compact sources. VLA observations at lambda = 2 cm, where the resolution approaches that of HST, reveals that the brightest unresolved radio source at 2 cm, which has been assumed to be a radio supernova, coincides with one of the compact HST sources. The implications of this will be discussed.

  2. In-air and pressurized water reactor environment fatigue experiments of 316 stainless steel to study the effect of environment on cyclic hardening

    NASA Astrophysics Data System (ADS)

    Mohanty, Subhasish; Soppet, William K.; Majumdar, Saurindranath; Natesan, Krishnamurti

    2016-05-01

    Argonne National Laboratory (ANL), under the sponsorship of Department of Energy's Light Water Reactor Sustainability (LWRS) program, is trying to develop a mechanistic approach for more accurate life estimation of LWR components. In this context, ANL has conducted many fatigue experiments under different test and environment conditions on type 316 stainless steel (316 SS) material which is widely used in the US reactors. Contrary to the conventional S ∼ N curve based empirical fatigue life estimation approach, the aim of the present DOE sponsored work is to develop an understanding of the material ageing issues more mechanistically (e.g. time dependent hardening and softening) under different test and environmental conditions. Better mechanistic understanding will help develop computer-based advanced modeling tools to better extrapolate stress-strain evolution of reactor components under multi-axial stress states and hence help predict their fatigue life more accurately. Mechanics-based modeling of fatigue such as by using finite element (FE) tools requires the time/cycle dependent material hardening properties. Presently such time-dependent material hardening properties are hardly available in fatigue modeling literature even under in-air conditions. Getting those material properties under PWR environment, are even harder. Through this work we made preliminary attempt to generate time/cycle dependent stress-strain data both under in-air and PWR water conditions for further study such as for possible development of material models and constitutive relations for FE model implementation. Although, there are open-ended possibility to further improve the discussed test methods and related material estimation techniques we anticipate that the data presented in this paper will help the metal fatigue research community particularly, the researchers who are dealing with mechanistic modeling of metal fatigue such as using FE tools. In this paper the fatigue experiments under different test and environment conditions and related stress-strain results for 316 SS are discussed.

  3. A climate-driven mechanistic population model of Aedes albopictus with diapause.

    PubMed

    Jia, Pengfei; Lu, Liang; Chen, Xiang; Chen, Jin; Guo, Li; Yu, Xiao; Liu, Qiyong

    2016-03-24

    The mosquito Aedes albopitus is a competent vector for the transmission of many blood-borne pathogens. An important factor that affects the mosquitoes' development and spreading is climate, such as temperature, precipitation and photoperiod. Existing climate-driven mechanistic models overlook the seasonal pattern of diapause, referred to as the survival strategy of mosquito eggs being dormant and unable to hatch under extreme weather. With respect to diapause, several issues remain unaddressed, including identifying the time when diapause eggs are laid and hatched under different climatic conditions, demarcating the thresholds of diapause and non-diapause periods, and considering the mortality rate of diapause eggs. Here we propose a generic climate-driven mechanistic population model of Ae. albopitus applicable to most Ae. albopictus-colonized areas. The new model is an improvement over the previous work by incorporating the diapause behaviors with many modifications to the stage-specific mechanism of the mosquitoes' life-cycle. monthly Container Index (CI) of Ae. albopitus collected in two Chinese cities, Guangzhou and Shanghai is used for model validation. The simulation results by the proposed model is validated with entomological field data by the Pearson correlation coefficient r (2) in Guangzhou (r (2) = 0.84) and in Shanghai (r (2) = 0.90). In addition, by consolidating the effect of diapause-related adjustments and temperature-related parameters in the model, the improvement is significant over the basic model. The model highlights the importance of considering diapause in simulating Ae. albopitus population. It also corroborates that temperature and photoperiod are significant in affecting the population dynamics of the mosquito. By refining the relationship between Ae. albopitus population and climatic factors, the model serves to establish a mechanistic relation to the growth and decline of the species. Understanding this relationship in a better way will benefit studying the transmission and the spatiotemporal distribution of mosquito-borne epidemics and eventually facilitating the early warning and control of the diseases.

  4. Global scale analysis and evaluation of an improved mechanistic representation of plant nitrogen and carbon dynamics in the Community Land Model (CLM)

    NASA Astrophysics Data System (ADS)

    Ghimire, B.; Riley, W. J.; Koven, C. D.; Randerson, J. T.; Mu, M.; Kattge, J.; Rogers, A.; Reich, P. B.

    2014-12-01

    In many ecosystems, nitrogen is the most limiting nutrient for plant growth and productivity. However mechanistic representation of nitrogen uptake linked to root traits, and functional nitrogen allocation among different leaf enzymes involved in respiration and photosynthesis is currently lacking in Earth System models. The linkage between nitrogen availability and plant productivity is simplistically represented by potential photosynthesis rates, and is subsequently downregulated depending on nitrogen supply and other nitrogen consumers in the model (e.g., nitrification). This type of potential photosynthesis rate calculation is problematic for several reasons. Firstly, plants do not photosynthesize at potential rates and then downregulate. Secondly, there is considerable subjectivity on the meaning of potential photosynthesis rates. Thirdly, there exists lack of understanding on modeling these potential photosynthesis rates in a changing climate. In addition to model structural issues in representing photosynthesis rates, the role of plant roots in nutrient acquisition have been largely ignored in Earth System models. For example, in CLM4.5, nitrogen uptake is linked to leaf level processes (e.g., primarily productivity) rather than root scale process involved in nitrogen uptake. We present a new plant model for CLM with an improved mechanistic presentation of plant nitrogen uptake based on root scale Michaelis Menten kinetics, and stronger linkages between leaf nitrogen and plant productivity by inferring relationships observed in global databases of plant traits (including the TRY database and several individual studies). We also incorporate improved representation of plant nitrogen leaf allocation, especially in tropical regions where significant over-prediction of plant growth and productivity in CLM4.5 simulations exist. We evaluate our improved global model simulations using the International Land Model Benchmarking (ILAMB) framework. We conclude that mechanistic representation of leaf-level nitrogen allocation and a theoretically consistent treatment of competition with belowground consumers leads to overall improvements in CLM4.5's global carbon cycling predictions.

  5. 'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Genn Saji

    2006-07-01

    In spite of industries' effort over the last 40 years, corrosion-related issues continue to be one of the largest unresolved problems for nuclear power plants worldwide. There are several types of strange corrosion phenomena from the point of view of our current understanding of corrosion science established in other fields. Some of these are IGSCC, PWSCC, AOA, and FAC (Erosion-Corrosion). Through studying and coping with diverse corrosion phenomena, the author believes that they share a common basis with respect to the assumed corrosion mechanism (e.g., 'local cell action' hypothesis). In general, local cell action is rarely severe since it producesmore » a fairly uniform corrosion. The 'long cell action' that transports electrons through structures far beyond the region of local cell corrosion activities has been identified as a basic mechanism in soil corrosion. If this mechanism is assumed in nuclear power plants, the structure becomes anodic in the area where the potential is less positive and cathodic where this potential is more positive. Metallic ions generated at anodic corrosion sites are transported to remote cathodic sites through the circulation of water and deposits as corrosion products. The SCC, FAC (E-C) and PWSCC occur in the anodic sites as the structure itself acts as a short-circuiting conductor between the two sites, the action is similar to a galvanic cell but in a very large scale. This situation is the same as a battery that has been short-circuited at the terminals. No apparent external potential difference exists between the two electrodes, but an electrochemical reaction is still taking place inside the battery cell with a large internal short current. In this example what is important is the potential difference between the local coolant and the surface of the structural material. Long cell action corrosion is likely enhancing the local cell action's anodic corrosion activities, such as SCC, FAC/E-C, and PWSCC. It tends to be more hazardous because of its localized nature compared with the local cell action corrosion. There exist various mechanisms (electrochemical cell configurations) that induce such potential differences, including: ionic concentration, aeration, temperature, flow velocity, radiation and corrosion potentials. In this paper, the author will discuss these potential differences and their relevance to the un-resolved corrosion issues in nuclear power plants. Due to the importance of this potential mechanism the author is calling for further verification experiments as a joint international project. (author)« less

  6. Seeking the chemical roots of darwinism: bridging between chemistry and biology.

    PubMed

    Pross, Addy

    2009-08-24

    Chemistry and biology are intimately connected sciences yet the chemistry-biology interface remains problematic and central issues regarding the very essence of living systems remain unresolved. In this essay we build on a kinetic theory of replicating systems that encompasses the idea that there are two distinct kinds of stability in nature-thermodynamic stability, associated with "regular" chemical systems, and dynamic kinetic stability, associated with replicating systems. That fundamental distinction is utilized to bridge between chemistry and biology by demonstrating that within the parallel world of replicating systems there is a second law analogue to the second law of thermodynamics, and that Darwinian theory may, through scientific reductionism, be related to that second law analogue. Possible implications of these ideas to the origin of life problem and the relationship between chemical emergence and biological evolution are discussed.

  7. Strong fields and neutral particle magnetic moment dynamics

    NASA Astrophysics Data System (ADS)

    Formanek, Martin; Evans, Stefan; Rafelski, Johann; Steinmetz, Andrew; Yang, Cheng-Tao

    2018-07-01

    Interaction of magnetic moment of point particles with external electromagnetic fields experiences unresolved theoretical and experimental discrepancies. In this work we point out several issues within relativistic quantum mechanics and QED and we describe effects related to a new covariant classical model of magnetic moment dynamics. Using this framework we explore the invariant acceleration experienced by neutral particles coupled to an external plane wave field through the magnetic moment: we study the case of ultrarelativistic Dirac neutrinos with magnetic moment in the range of 10‑11 to 10‑20 μ B; and we address the case of slowly moving neutrons. We explore how critical accelerations for neutrinos can be experimentally achieved in laser pulse interactions. The radiation of accelerated neutrinos can serve as an important test distinguishing between Majorana and Dirac nature of neutrinos.

  8. Prospects for Breakthrough Propulsion From Physics

    NASA Technical Reports Server (NTRS)

    Millis, Marc G.

    2004-01-01

    "Space drives", "Warp drives", and "Wormholes:" these concepts may sound like science fiction, but they are being written about in reputable journals. To assess the implications of these emerging prospects for future spaceflight, NASA supported the Breakthrough Propulsion Physics Project from 1996 through 2002. This Project has three grand challenges: (1) Discover propulsion that eliminates the need for propellant; (2) Discover methods to achieve hyper-fast travel; and (3) Discover breakthrough methods to power spacecraft. Because these challenges are presumably far from fruition, and perhaps even impossible, a special emphasis is placed on selecting incremental and affordable research that addresses the critical issues behind these challenges. Of 16 incremental research tasks completed by the project and from other sponsors, about a third were found not to be viable, a quarter have clear opportunities for sequels, and the rest remain unresolved.

  9. Seismic verification of nuclear plant equipment anchorage: Volume 1, Development of anchorage guidelines: Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Czarnecki, R M

    1987-05-01

    Guidelines have been developed to evaluate the seismic adequacy of the anchorage of various classes of electrical and mechanical equipment in nuclear power plants covered by NRC Unresolved Safety Issue A-46. The guidelines consist of screening tables that give the seismic anchorage capacity as a function of key equipment and anchorage fasteners, inspection checklists for field verification of anchorage adequacy, and provisions for outliers that can be used to further investigate anchorages that cannot be verified in the field. The screening tables are based on an analysis of the anchorage forces developed by common equipment types and on strength criteriamore » to quantify the holding power of anchor bolts and welds. The strength criteria for expansion anchor bolts were developed by collecting and analyzing a large quantity of test data.« less

  10. Seismic verification of nuclear plant equipment anchorage: Volume 2, Anchorage inspection workbook: Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Czarnecki, R M

    1987-05-01

    Guidelines have been developed to evaluate the seismic adequacy of the anchorage of various classes of electrical and mechanical equipment in nuclear power plants covered by NRC Unresolved Safety Issue A-46. The guidelines consist of screening tables that give the seismic anchorage capacity as a function of key equipment and anchorage fasteners, inspection checklists for field verification of anchorage adequacy, and provisions for outliers that can be used to further investigate anchorages that cannot be verified in the field. The screening tables are based on an analysis of the anchorage forces developed by common equipment types and on strength criteriamore » to quantify the holding power of anchor bolts and welds. The strength criteria for expansion anchor bolts were developed by collecting and analyzing a large quantity of test data.« less

  11. Value reprioritization in psychoanalysis.

    PubMed

    Horowitz, Mardi J

    2009-12-01

    As psychoanalysts, we sometimes seem to regard values as radioactive materials that must be handled with heavy lead gloves. But the gloves should not be so thick that they interfere with the goal of sorting out values. Reasons for our hesitation to deal with issues related to values may include real disagreements with the morals of a patient, a fear of evoking unproductive and negative emotional states, and our own unresolved conflicts about value dilemmas. Psychoanalytic technique should at times include clear verbal statements of values. By being explicit about what is often implicit, we can help our patients in their work of ameliorating harsh, primitive, and critical attitudes and to self-own rules, principles, and codes of conduct. A patient with reprioritized personal values may then function with heightened interpersonal compassion, kindness, and cooperation, gaining in return love, intimacy, respect, and self-esteem.

  12. Protecting the rights of school children with diabetes.

    PubMed

    Wood, James M

    2013-03-01

    School children with diabetes are facing increasing difficulties in receiving care during the school day. Despite theexistence of federal statutes ensuring their rights to a free, appropriate public education, many school districts throughout the country do little, if anything, to ensure that their condition is treated throughout the school day. The chronic shortage of school nurses has resulted in hardships on families, relatives, and friends to ensure that care, including insulin, is timely and appropriately provided. While many states have taken measures to provide care by unlicensed trained volunteers, efforts to accomplish this in California have resulted in prolonged litigation. A variety of nursing organizations oppose all efforts to train unlicensed volunteers, arguing that such is not permitted by California law. The issue is unresolved and currently pending in the California Supreme Court. © 2013 Diabetes Technology Society.

  13. Biodegradable Photonic Melanoidin for Theranostic Applications.

    PubMed

    Lee, Min-Young; Lee, Changho; Jung, Ho Sang; Jeon, Mansik; Kim, Ki Su; Yun, Seok Hyun; Kim, Chulhong; Hahn, Sei Kwang

    2016-01-26

    Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

  14. Salbutamol in paediatrics: pharmacology, prescribing and controversies.

    PubMed

    Andrzejowski, Paul; Carroll, Will

    2016-08-01

    Salbutamol has become a key drug in respiratory medicine since it was first developed by Sir David Jack et al in 1968, 5000 years after the β agonist ephedrine was first used in its raw form, as the Ma Huang herb in Chinese medicine to treat asthma. It is one of the most commonly encountered medicines in paediatric practice and the authors have found that an understanding of its pharmacology in clinical practice is incredibly helpful. In this article, we discuss its pharmacology and pharmacodynamics, practical prescribing points and some unresolved issues surrounding its use, which should serve to provide an essential working knowledge for the busy paediatrician. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Climate-Rotation Feedback on Mars

    NASA Technical Reports Server (NTRS)

    Bills, Bruce G.

    1999-01-01

    A new model is presented for the coupled evolution of climate and rotation, as applied to Mars. It has long been appreciated that changes in the orbital and rotational geometry of Mars will influence the seasonal and latitudinal pattern of insolation, and this will likely dominate climatic fluctuations on time scales of 10(exp 5) to 10(exp 7) years. Equally important, but less widely appreciated, is the influence climatic change can have on rotational dynamics. The primary means by which climate influences rotation is via its influence on transport of mass (volatiles and dust) into and out of the polar regions. Many important issues remain unresolved: What are the ages of the polar caps? What climatic periods are recorded in the polar layered deposits? What is the long term obliquity history? Additional information is contained in the original extended abstract.

  16. Accelerating Plasma Mirrors to Investigate the Black Hole Information Loss Paradox

    NASA Astrophysics Data System (ADS)

    Chen, Pisin; Mourou, Gerard

    2017-01-01

    The question of whether Hawking evaporation violates unitarity, and therefore results in the loss of information, has remained unresolved since Hawking's seminal discovery. To date, the investigations have remained mostly theoretical since it is almost impossible to settle this paradox through direct astrophysical black hole observations. Here, we point out that relativistic plasma mirrors can be accelerated drastically and stopped abruptly by impinging intense x-ray pulses on solid plasma targets with a density gradient. This is analogous to the late time evolution of black hole Hawking evaporation. A conception of such an experiment is proposed and a self-consistent set of physical parameters is presented. Critical issues, such as how the black hole unitarity may be preserved, can be addressed through the entanglement between the analog Hawking radiation photons and their partner modes.

  17. Long-lived efficient delayed fluorescence organic light-emitting diodes using n-type hosts.

    PubMed

    Cui, Lin-Song; Ruan, Shi-Bin; Bencheikh, Fatima; Nagata, Ryo; Zhang, Lei; Inada, Ko; Nakanotani, Hajime; Liao, Liang-Sheng; Adachi, Chihaya

    2017-12-21

    Organic light-emitting diodes have become a mainstream display technology because of their desirable features. Third-generation electroluminescent devices that emit light through a mechanism called thermally activated delayed fluorescence are currently garnering much attention. However, unsatisfactory device stability is still an unresolved issue in this field. Here we demonstrate that electron-transporting n-type hosts, which typically include an acceptor moiety in their chemical structure, have the intrinsic ability to balance the charge fluxes and broaden the recombination zone in delayed fluorescence organic electroluminescent devices, while at the same time preventing the formation of high-energy excitons. The n-type hosts lengthen the lifetimes of green and blue delayed fluorescence devices by > 30 and 1000 times, respectively. Our results indicate that n-type hosts are suitable to realize stable delayed fluorescence organic electroluminescent devices.

  18. Accelerating Plasma Mirrors to Investigate the Black Hole Information Loss Paradox.

    PubMed

    Chen, Pisin; Mourou, Gerard

    2017-01-27

    The question of whether Hawking evaporation violates unitarity, and therefore results in the loss of information, has remained unresolved since Hawking's seminal discovery. To date, the investigations have remained mostly theoretical since it is almost impossible to settle this paradox through direct astrophysical black hole observations. Here, we point out that relativistic plasma mirrors can be accelerated drastically and stopped abruptly by impinging intense x-ray pulses on solid plasma targets with a density gradient. This is analogous to the late time evolution of black hole Hawking evaporation. A conception of such an experiment is proposed and a self-consistent set of physical parameters is presented. Critical issues, such as how the black hole unitarity may be preserved, can be addressed through the entanglement between the analog Hawking radiation photons and their partner modes.

  19. Valproic acid ameliorates C. elegans dopaminergic neurodegeneration with implications for ERK-MAPK signaling.

    PubMed

    Kautu, Bwarenaba B; Carrasquilla, Alejandro; Hicks, Matthew L; Caldwell, Kim A; Caldwell, Guy A

    2013-04-29

    Parkinson's disease (PD) is a currently incurable neurodegenerative disorder that affects the aging population. The loss of dopaminergic neurons in the substantia nigra is one of the pathological features of PD. The precise causes of PD remain unresolved but evidence supports both environmental and genetic contributions. Current efforts for the treatment of PD are directed toward the discovery of compounds that show promise in impeding age-dependent neurodegeneration in PD patients. Alpha-synuclein (α-Syn) is a human protein that is mutated in specific populations of patients with familial PD. Overexpression of α-Syn in animal models of PD replicates key symptoms of PD, including neurodegeneration. Here, we use the nematode Caenorhabditis elegans as a model system, whereby α-Syn toxicity causes dopaminergic neurodegeneration, to test the capacity of valproic acid (VA) to protect neurons. The results of our study showed that treatment of nematodes with moderate concentrations of VA significantly protects dopaminergic neurons against α-Syn toxicity. Consistent with previously established knowledge related to the mechanistic action of VA in the cell, we showed through genetic analysis that the neuroprotection conferred by VA is inhibited by cell-specific depletion of the C. elegans ortholog of the MAP extracellular signal-regulated kinase (ERK), MPK-1, in the dopaminergic neurons. These findings suggest that VA may exert its neuroprotective effect via ERK-MAPK, or alternately could act with MAPK signaling to additively provide dopaminergic neuroprotection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Order–Disorder Transitions Govern Kinetic Cooperativity and Allostery of Monomeric Human Glucokinase

    PubMed Central

    Bruschweiler-Li, Lei; Miller, Brian G.; Brüschweiler, Rafael

    2012-01-01

    Glucokinase (GCK) catalyzes the rate-limiting step of glucose catabolism in the pancreas, where it functions as the body's principal glucose sensor. GCK dysfunction leads to several potentially fatal diseases including maturity–onset diabetes of the young type II (MODY-II) and persistent hypoglycemic hyperinsulinemia of infancy (PHHI). GCK maintains glucose homeostasis by displaying a sigmoidal kinetic response to increasing blood glucose levels. This positive cooperativity is unique because the enzyme functions exclusively as a monomer and possesses only a single glucose binding site. Despite nearly a half century of research, the mechanistic basis for GCK's homotropic allostery remains unresolved. Here we explain GCK cooperativity in terms of large-scale, glucose-mediated disorder–order transitions using 17 isotopically labeled isoleucine methyl groups and three tryptophan side chains as sensitive nuclear magnetic resonance (NMR) probes. We find that the small domain of unliganded GCK is intrinsically disordered and samples a broad conformational ensemble. We also demonstrate that small-molecule diabetes therapeutic agents and hyperinsulinemia-associated GCK mutations share a strikingly similar activation mechanism, characterized by a population shift toward a more narrow, well-ordered ensemble resembling the glucose-bound conformation. Our results support a model in which GCK generates its cooperative kinetic response at low glucose concentrations by using a millisecond disorder–order cycle of the small domain as a “time-delay loop,” which is bypassed at high glucose concentrations, providing a unique mechanism to allosterically regulate the activity of human GCK under physiological conditions. PMID:23271955

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