79 research outputs found

    Work Avoidance as a Manifestation of Hostility, Helplessness, and Boredom

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    Work avoidance is a term that describes the behavior of students who seem to make little effort to understand or complete academic tasks. Although the condition has been described in earlier studies, the causes of work avoidance have not been explored. In this study, grades 5 and 6 students who were identified as work avoidant were interviewed to determine the causes of their work avoidance. It was hypothesized that boredom, hostility, and helplessness were three possible reasons for students not exerting effort. Students' protocols indicated that they do withdraw effort for several reasons: because they are bored, as an expression of hostility toward the teacher, or because of feelings of helplessness.L'évitement du travail est une expression qui décrit le comportement d'élèves qui ne semblent consentir que peu d'efforts pour comprendre ou compléter des activités académiques. Alors que des études précédentes ont déjà décrit le phénomène, on ne s'était pas encore penché sur ses causes. Pendant cette étude, des élèves de la cinquième et la sixième année qu'on avait caractérisés comme jeunes qui évitaient le travail ont été passés en entrevue dans le but d'identifier les causes de leur comportement. Comme éléments provocateurs possibles, les auteurs avaient proposé l'ennui, l'hostilité et un sentiment d'impuissance. Selon les protocoles des élèves, ceux-ci renoncent à l'effort pour plusieurs raisons: parce qu'ils s'ennuient, comme expression d'hostilité envers l'enseignant ou parce qu'ils vivent des sentiments d'impuissance

    Non-linear properties of supercooled liquids in the system Na2O---SiO2

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    The physical properties, viscosity, density, heat capacity and thermal expansivity, of relaxed supercooled liquids in the temperature range just above the glass transition have been determined for ten compositions along the compositional binary Na2O---SiO2, in the range of 2–45 mole% Na2O, by a combination of scanning calorimetry, dilatometry and micropenetration viscometry. The viscosity, density, heat capacity and thermal expansivity in the glassy state have also been determined. The heat capacities illustrate a linear composition dependence for the glassy state and a smooth but strongly non-linear composition dependence for the supercooled liquid state. The thermal expansivities were determined by dilatometry up to the glass transition and, by a normalized comparison of relaxation behavior in the glass transition interval, to temperatures 50°C above the glass transition. The expansivity is a linear function of the molar composition in the glass but a strongly non-linear function of molar composition in the supercooled liquid. The viscosity data just above the glass transition temperature, combined with data from high temperature using the concentric cylinder method, illustrate that the composition dependence of viscosity is strongly non-linear and exhibits an inflection as a function of composition. The glass transition temperature, taken as the peak temperature of the calorimetric measurements, is not in general an isokom in this system. The data for these property determinations in the Na2O---SiO2 system provide much improved constraints on the partial molar properties of SiO2 liquid and partial molar properties of the SiO2 component in silicate melts. The complex behavior of the transport properties, i.e. the glass transition temperature and the viscosity, point to complexities in viscous flow beyond that of simple binary mixing of the Na2O and SiO2 components

    Closing the Coverage Gaps: Reducing Health Insurance Disparities in Massachusetts

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    Massachusetts has been exemplary in developing health insurance coverage policies to cover its residents. By 2019, the state's uninsurance rate was 3.0 percent, the lowest rate in the nation, representing about 204,000 uninsured residents. While the state's overall uninsured rate at a given point in time is low, more than twice as many people - 503,000, or 7.3 percent of the population - experienced a gap in coverage over the previous twelve months. And importantly, not all groups benefit equally. People who are Black or Hispanic, or who have lower incomes, experience significantly higher rates of uninsurance than the state population overall. As a result, these groups are more likely to face access barriers and financial insecurity associated with being uninsured.The purpose of this report is to begin charting a course toward closing the coverage gaps in Massachusetts, with a particular focus on creating a more racially and ethnically equitable system of coverage. The report and accompanying infographics describe the people in Massachusetts without health insurance and the barriers to coverage they face, including affordability, administrative complexity, and immigration, language, and cultural barriers. It then proposes a menu of policy options that address the specific circumstances in Massachusetts. The proposed options are meant to inform a statewide conversation about the best approaches to closing the remaining coverage gaps in Massachusetts and removing structural barriers that result in racial and ethnic disparities in health insurance coverage

    Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource

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    Supplemental Data Supplemental Data include 65 figures and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2017.04.015. Supplemental Data Document S1. Figures S1–S65 Download Document S2. Article plus Supplemental Data Download Web Resources ClinGen, https://www.clinicalgenome.org/ ClinGen Gene Curation, https://www.clinicalgenome.org/working-groups/gene-curation/ ClinGen Gene Curation SOP, https://www.clinicalgenome.org/working-groups/gene-curation/projects-initiatives/gene-disease-clinical-validity-sop/ ClinGen Knowledge Base, https://search.clinicalgenome.org/kb/agents/sign_up OMIM, http://www.omim.org/ Orphanet, http://www.orpha.net/consor/cgi-bin/index.php With advances in genomic sequencing technology, the number of reported gene-disease relationships has rapidly expanded. However, the evidence supporting these claims varies widely, confounding accurate evaluation of genomic variation in a clinical setting. Despite the critical need to differentiate clinically valid relationships from less well-substantiated relationships, standard guidelines for such evaluation do not currently exist. The NIH-funded Clinical Genome Resource (ClinGen) has developed a framework to define and evaluate the clinical validity of gene-disease pairs across a variety of Mendelian disorders. In this manuscript we describe a proposed framework to evaluate relevant genetic and experimental evidence supporting or contradicting a gene-disease relationship and the subsequent validation of this framework using a set of representative gene-disease pairs. The framework provides a semiquantitative measurement for the strength of evidence of a gene-disease relationship that correlates to a qualitative classification: “Definitive,” “Strong,” “Moderate,” “Limited,” “No Reported Evidence,” or “Conflicting Evidence.” Within the ClinGen structure, classifications derived with this framework are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. Detailed guidance for utilizing this framework and access to the curation interface is available on our website. This evidence-based, systematic method to assess the strength of gene-disease relationships will facilitate more knowledgeable utilization of genomic variants in clinical and research settings

    Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men

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    Background. This study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM). Methods. Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [ preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined. Results. Twenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC 90 ) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses. Conclusions. High PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis

    Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus—A Mechanism of Action for Anti-Influenza Agents

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    Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds

    International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database - the quality controlled standard tool for routine identification of human and animal pathogenic fungi

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    Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.This study was supported by an National Health and Medical Research Council of Australia (NH&MRC) grant [#APP1031952] to W Meyer, S Chen, V Robert, and D Ellis; CNPq [350338/2000-0] and FAPERJ [E-26/103.157/2011] grants to RM Zancope-Oliveira; CNPq [308011/2010-4] and FAPESP [2007/08575-1] Fundacao de Amparo Pesquisa do Estado de So Paulo (FAPESP) grants to AL Colombo; PEst-OE/BIA/UI4050/2014 from Fundacao para a Ciencia e Tecnologia (FCT) to C Pais; the Belgian Science Policy Office (Belspo) to BCCM/IHEM; the MEXBOL program of CONACyT-Mexico, [ref. number: 1228961 to ML Taylor and [122481] to C Toriello; the Institut Pasteur and Institut de Veil le Sanitaire to F Dromer and D Garcia-Hermoso; and the grants from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and the Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) to CM de Almeida Soares and JA Parente Rocha. I Arthur would like to thank G Cherian, A Higgins and the staff of the Molecular Diagnostics Laboratory, Division of Microbiology and Infectious Diseases, Path West, QEII Medial Centre. Dromer would like to thank for the technical help of the sequencing facility and specifically that of I, Diancourt, A-S Delannoy-Vieillard, J-M Thiberge (Genotyping of Pathogens and Public Health, Institut Pasteur). RM Zancope-Oliveira would like to thank the Genomic/DNA Sequencing Platform at Fundacao Oswaldo Cruz-PDTIS/FIOCRUZ [RPT01A], Brazil for the sequencing. B Robbertse and CL Schoch acknowledge support from the Intramural Research Program of the NIH, National Library of Medicine. T Sorrell's work is funded by the NH&MRC of Australia; she is a Sydney Medical School Foundation Fellow.info:eu-repo/semantics/publishedVersio

    Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

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    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine
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