186 research outputs found

    Health Locus of Control and Assimilation of Cervical Cancer Information in Deaf Women

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    This study assessed the relationship between Deaf women's internal health locus of control (IHLC) and their cervical cancer knowledge acquisition and retention. A blind, randomized trial evaluated Deaf women's (N = 130) baseline cancer knowledge and knowledge gained and retained from an educational intervention, in relation to their IHLC. The Multidimensional Health Locus of Control scales measured baseline IHLC, and a cervical cancer knowledge survey evaluated baseline to post-intervention knowledge change. Women's IHLC did not significantly predict greater cervical cancer knowledge at baseline or over time. IHLC does not appear to be a characteristic that must be considered when creating Deaf women's cancer education programs

    Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a cell-penetrating caspase-activatable peptide probe

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    Peptide probes for imaging retinal ganglion cell (RGC) apoptosis consist of a cell-penetrating peptide targeting moiety and a fluorophore-quencher pair flanking an effector caspase consensus sequence. Using ex vivo fluorescence imaging, we previously validated the capacity of these probes to identify apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D-aspartate (NMDA)-induced neurotoxicity. Herein, using TcapQ488, a new probe designed and synthesized for compatibility with clinically-relevant imaging instruments, and real time imaging of a live rat RGC degeneration model, we fully characterized time- and dose-dependent probe activation, signal-to-noise ratios, and probe safety profiles in vivo. Adult rats received intravitreal injections of four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus imaging was performed sequentially in vivo using a confocal scanning laser ophthalmoscope and individual RGCs displaying activated probe were counted and analyzed. Rats also underwent electroretinography following intravitreal injection of probe. In vivo fluorescence fundus imaging revealed distinct single-cell probe activation as an indicator of RGC apoptosis induced by intravitreal NMDA injection that corresponded to the identical cells observed in retinal flat mounts of the same eye. Peak activation of probe in vivo was detected 12 hours post probe injection. Detectable fluorescent RGCs increased with increasing NMDA concentration; sensitivity of detection generally increased with increasing TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following intravitreal injections of TcapQ488 showed no significant difference compared with control injections. We optimized the signal-to-noise ratio of a caspase-activatable cell penetrating peptide probe for quantitative non-invasive detection of RGC apoptosis in vivo. Full characterization of probe performance in this setting creates an important in vivo imaging standard for functional evaluation of future probe analogues and provides a basis for extending this strategy into glaucoma-specific animal models

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

    Effectiveness analysis of resistance and tolerance to infection

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    <p>Abstract</p> <p>Background</p> <p>Tolerance and resistance provide animals with two distinct strategies to fight infectious pathogens and may exhibit different evolutionary dynamics. However, few studies have investigated these mechanisms in the case of animal diseases under commercial constraints.</p> <p>Methods</p> <p>The paper proposes a method to simultaneously describe (1) the dynamics of transmission of a contagious pathogen between animals, (2) the growth and death of the pathogen within infected hosts and (3) the effects on their performances. The effectiveness of increasing individual levels of tolerance and resistance is evaluated by the number of infected animals and the performance at the population level.</p> <p>Results</p> <p>The model is applied to a particular set of parameters and different combinations of values. Given these imputed values, it is shown that higher levels of individual tolerance should be more effective than increased levels of resistance in commercial populations. As a practical example, a method is proposed to measure levels of animal tolerance to bovine mastitis.</p> <p>Conclusions</p> <p>The model provides a general framework and some tools to maximize health and performances of a population under infection. Limits and assumptions of the model are clearly identified so it can be improved for different epidemiological settings.</p

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

    Genome-Wide Association Data Reveal a Global Map of Genetic Interactions among Protein Complexes

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    This work demonstrates how gene association studies can be analyzed to map a global landscape of genetic interactions among protein complexes and pathways. Despite the immense potential of gene association studies, they have been challenging to analyze because most traits are complex, involving the combined effect of mutations at many different genes. Due to lack of statistical power, only the strongest single markers are typically identified. Here, we present an integrative approach that greatly increases power through marker clustering and projection of marker interactions within and across protein complexes. Applied to a recent gene association study in yeast, this approach identifies 2,023 genetic interactions which map to 208 functional interactions among protein complexes. We show that such interactions are analogous to interactions derived through reverse genetic screens and that they provide coverage in areas not yet tested by reverse genetic analysis. This work has the potential to transform gene association studies, by elevating the analysis from the level of individual markers to global maps of genetic interactions. As proof of principle, we use synthetic genetic screens to confirm numerous novel genetic interactions for the INO80 chromatin remodeling complex

    Quorum Sensing Influences Vibrio harveyi Growth Rates in a Manner Not Fully Accounted For by the Marker Effect of Bioluminescence

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    The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy. quorum mutants. growth rate can be either positive or negative and includes both bioluminescence-dependent and independent components. Bioluminescence tends to slow growth rate but not enough to account for the effects of quorum sensing on growth rate

    Mining for genotype-phenotype relations in Saccharomyces using partial least squares

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    <p>Abstract</p> <p>Background</p> <p>Multivariate approaches are important due to their versatility and applications in many fields as it provides decisive advantages over univariate analysis in many ways. Genome wide association studies are rapidly emerging, but approaches in hand pay less attention to multivariate relation between genotype and phenotype. We introduce a methodology based on a BLAST approach for extracting information from genomic sequences and Soft- Thresholding Partial Least Squares (ST-PLS) for mapping genotype-phenotype relations.</p> <p>Results</p> <p>Applying this methodology to an extensive data set for the model yeast <it>Saccharomyces cerevisiae</it>, we found that the relationship between genotype-phenotype involves surprisingly few genes in the sense that an overwhelmingly large fraction of the phenotypic variation can be explained by variation in less than 1% of the full gene reference set containing 5791 genes. These phenotype influencing genes were evolving 20% faster than non-influential genes and were unevenly distributed over cellular functions, with strong enrichments in functions such as cellular respiration and transposition. These genes were also enriched with known paralogs, stop codon variations and copy number variations, suggesting that such molecular adjustments have had a disproportionate influence on <it>Saccharomyces </it>yeasts recent adaptation to environmental changes in its ecological niche.</p> <p>Conclusions</p> <p>BLAST and PLS based multivariate approach derived results that adhere to the known yeast phylogeny and gene ontology and thus verify that the methodology extracts a set of fast evolving genes that capture the phylogeny of the yeast strains. The approach is worth pursuing, and future investigations should be made to improve the computations of genotype signals as well as variable selection procedure within the PLS framework.</p

    Review on the validity of self-report to assess work-related diseases

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    Self-report is an efficient and accepted means of assessing population characteristics, risk factors, and diseases. Little is known on the validity of self-reported work-related illness as an indicator of the presence of a work-related disease. This study reviews the evidence on (1) the validity of workers' self-reported illness and (2) on the validity of workers' self-assessed work relatedness of an illness. A systematic literature search was conducted in four databases (Medline, Embase, PsycINFO and OSH-Update). Two reviewers independently performed the article selection and data extraction. The methodological quality of the studies was evaluated, levels of agreement and predictive values were rated against predefined criteria, and sources of heterogeneity were explored. In 32 studies, workers' self-reports of health conditions were compared with the "reference standard" of expert opinion. We found that agreement was mainly low to moderate. Self-assessed work relatedness of a health condition was examined in only four studies, showing low-to-moderate agreement with expert assessment. The health condition, type of questionnaire, and the case definitions for both self-report and reference standards influence the results of validation studies. Workers' self-reported illness may provide valuable information on the presence of disease, although the generalizability of the findings is limited primarily to musculoskeletal and skin disorders. For case finding in a population at risk, e.g., an active workers' health surveillance program, a sensitive symptom questionnaire with a follow-up by a medical examination may be the best choice. Evidence on the validity of self-assessed work relatedness of a health condition is scarce. Adding well-developed questions to a specific medical diagnosis exploring the relationship between symptoms and work may be a good strateg

    Regularity of center-of-pressure trajectories depends on the amount of attention invested in postural control

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    The influence of attention on the dynamical structure of postural sway was examined in 30 healthy young adults by manipulating the focus of attention. In line with the proposed direct relation between the amount of attention invested in postural control and regularity of center-of-pressure (COP) time series, we hypothesized that: (1) increasing cognitive involvement in postural control (i.e., creating an internal focus by increasing task difficulty through visual deprivation) increases COP regularity, and (2) withdrawing attention from postural control (i.e., creating an external focus by performing a cognitive dual task) decreases COP regularity. We quantified COP dynamics in terms of sample entropy (regularity), standard deviation (variability), sway-path length of the normalized posturogram (curviness), largest Lyapunov exponent (local stability), correlation dimension (dimensionality) and scaling exponent (scaling behavior). Consistent with hypothesis 1, standing with eyes closed significantly increased COP regularity. Furthermore, variability increased and local stability decreased, implying ineffective postural control. Conversely, and in line with hypothesis 2, performing a cognitive dual task while standing with eyes closed led to greater irregularity and smaller variability, suggesting an increase in the “efficiency, or “automaticity” of postural control”. In conclusion, these findings not only indicate that regularity of COP trajectories is positively related to the amount of attention invested in postural control, but also substantiate that in certain situations an increased internal focus may in fact be detrimental to postural control
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