598 research outputs found

    Microbial Foodborne Disease: Hospitalizations, Medical Costs and Potential Demand for Safer Food

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    Food Consumption/Nutrition/Food Safety, Health Economics and Policy,

    Chronically shortened rod outer segments accompany photoreceptor cell death in Choroideremia

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    X-linked choroideremia (CHM) is a disease characterized by gradual retinal degeneration caused by loss of the Rab Escort Protein, REP1. Despite partial compensation by REP2 the disease is characterized by prenylation defects in multiple members of the Rab protein family that are master regulators of membrane traffic. Remarkably, the eye is the only organ affected in CHM patients, possibly because of the huge membrane traffic burden of the post mitotic photoreceptors, which synthesise outer segments, and the adjacent retinal pigment epithelium that degrades the spent portions each day. In this study, we aimed to identify defects in membrane traffic that might lead to photoreceptor cell death in CHM. In a heterozygous null female mouse model of CHM (Chmnull/WT), degeneration of the photoreceptor layer was clearly evident from increased numbers of TUNEL positive cells compared to age matched controls, small numbers of cells exhibiting signs of mitochondrial stress and greatly increased microglial infiltration. However, most rod photoreceptors exhibited remarkably normal morphology with well-formed outer segments and no discernible accumulation of transport vesicles in the inner segment. The major evidence of membrane trafficking defects was a shortening of rod outer segments that was evident at 2 months of age but remained constant over the period during which the cells die. A decrease in rhodopsin density found in the outer segment may underlie the outer segment shortening but does not lead to rhodopsin accumulation in the inner segment. Our data argue against defects in rhodopsin transport or outer segment renewal as triggers of cell death in CHM.publishersversionpublishe

    Race differences in the physical and psychological impact of hypertension labeling

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    Background - Blood pressure screening is an important component of cardiovascular disease prevention, but a hypertension diagnosis (i.e., label) can have unintended negative effects on patients' well-being. Despite persistent disparities in hypertension prevalence and outcomes, whether the impact of labeling differs by race is unknown. The purpose of this study was to evaluate possible race differences in the relationship between hypertension labeling and health-related quality of life and depression. Methods - The sample included 308 normotensive and unmedicated hypertensive subjects from the Neighborhood Study of Blood Pressure and Sleep, a cross-sectional study conducted between 1999 and 2003. Labeled hypertension was defined (by self-report) as having been diagnosed with high blood pressure or prescribed antihypertensive medications. Effects of labeling and race on self-reported physical and mental health and depressive symptoms were tested using multivariate analysis of covariance, controlling for age, sex, body mass index (BMI), previous medication use, and “true” hypertension status, defined by average daytime ambulatory blood pressure (ABP). Results - Both black and white subjects who had been labeled as hypertensive reported similarly poorer physical health than unlabeled subjects (P = 0.001). However, labeling was associated with poorer mental health and greater depressive symptoms only among blacks (Ps < 0.05 for the interactions). These findings were not explained by differences in socioeconomic status. Conclusions - These results are consistent with previous studies showing negative effects of hypertension labeling, and demonstrate important race differences in these effects. Clinical approaches to communicating diagnostic information that avoid negative effects on well-being are needed, and may require tailoring to patient characteristics such as race

    A global assessment of surveillance methods for dominant malaria vectors

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    The epidemiology of human malaria differs considerably between and within geographic regions due, in part, to variability in mosquito species behaviours. Recently, the WHO emphasised stratifying interventions using local surveillance data to reduce malaria. The usefulness of vector surveillance is entirely dependent on the biases inherent in the sampling methods deployed to monitor mosquito populations. To understand and interpret mosquito surveillance data, the frequency of use of malaria vector collection methods was analysed from a georeferenced vector dataset (> 10,000 data records), extracted from 875 manuscripts across Africa, the Americas and the Asia-Pacific region. Commonly deployed mosquito collection methods tend to target anticipated vector behaviours in a region to maximise sample size (and by default, ignoring other behaviours). Mosquito collection methods targeting both host-seeking and resting behaviours were seldomly deployed concurrently at the same site. A balanced sampling design using multiple methods would improve the understanding of the range of vector behaviours, leading to improved surveillance and more effective vector control

    Design of Force Fields from Data at Finite Temperature

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    We investigate the problem of how to obtain the force field between atoms of an experimentally determined structure. We show how this problem can be efficiently solved, even at finite temperature, where the position of the atoms differs substantially from the ground state. We apply our method to systems modeling proteins and demonstrate that the correct potentials can be recovered even in the presence of thermal noise.Comment: 10 pages, 1 postcript figure, Late

    Non-routine mathematical problem-solving: Creativity, engagement, and intuition of STEM tertiary students

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    This study set out to evaluate an intervention that introduced a period of non-routine problem-solving into tertiary STEM lectures at four tertiary institutions in New Zealand for 683 students. The aim was twofold: to attempt to increase student engagement and to introduce them to the kind of domain-free abstract reasoning that involves critical, creative, and innovative thinking. This study was conducted using a mixed-methods approach, utilizing different types of instruments to gather data: comprehensive student pre- and post-test questionnaires, a content validation survey for the questionnaires, focus group interviews (student participants), open-ended questionnaire (lecturer participants), and naturalistic class observations. The main findings are as follows. Students' behavioural engagement was significantly greater during the intervention. Perceptions of the utility value of the activity improved at the end of the semester for all students. There were no significant changes in students' convergent thinking (problem-solving), intuition, or creativity (originality, fluency, and elaboration traits of the divergent thinking) during the course, probably due to the relatively short timescale of the intervention. However, overall, the results of the investigation suggest that with a relatively small effort, teachers can improve STEM student engagement by devoting a few minutes per lecture on non-routine problem-solving. This is something that can be easily implemented, even by those who primarily teach in a traditional lecturing style

    Pills, PrEP, and Pals: Adherence, Stigma, Resilience, Faith and the Need to Connect Among Minority Women With HIV/AIDS in a US HIV Epicenter

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    Background: Ending HIV/AIDS in the United States requires tailored interventions. This study is part of a larger investigation to design mCARES, a mobile technology-based, adherence intervention for ethnic minority women with HIV (MWH).Objective: To understand barriers and facilitators of care adherence (treatment and appointment) for ethnic MWH; examine the relationship between these factors across three ethnic groups; and, explore the role of mobile technologies in care adherence.Methods: Cross-sectional, mixed-methods data were collected from a cohort of African-American, Hispanic-American and Haitian-American participants. Qualitative data were collected through a focus group (n = 8) to assess barriers and facilitators to care adherence. Quantitative data (n = 48) surveyed women on depressive symptomology (PHQ-9), HIV-related stigma (HSS) and resiliency (CD-RISC25). We examined the relationships between these factors and adherence to treatment and care and across groups.Findings: Qualitative analyses revealed that barriers to treatment and appointment adherence were caregiver-related stressors (25%) and structural issues (25%); routinization (30%) and religion/spirituality (30%) promoted adherence to treatment and care. Caregiver role was both a hindrance (25%) and promoter (20%) of adherence to treatment and appointments. Quantitatively, HIV-related stigma differed by ethnic group; Haitian-Americans endorsed the highest levels while African-Americans endorsed the lowest. Depression correlated to stigma (R = 0.534; p &lt; 0.001) and resiliency (R = −0.486; p &lt; 0.001). Across ethnic groups, higher depressive symptomology and stigma were related to viral non-suppression (p &lt; 0.05)—a treatment adherence marker; higher resiliency was related to viral suppression. Among Hispanic-Americans, viral non-suppression was related to depression (p &lt; 0.05), and among African-Americans, viral suppression was related to increased resiliency (p &lt; 0.04).Conclusion: Multiple interrelated barriers to adherence were identified. These findings on ethnic group-specific differences underscore the importance of implementing culturally-competent interventions. While privacy and confidentiality were of concern, participants suggested additional intervention features and endorsed the use of mCARES as a strategy to improve adherence to treatment and appointments

    Independent test assessment using the extreme value distribution theory

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    Abstract The new generation of whole genome sequencing platforms offers great possibilities and challenges for dissecting the genetic basis of complex traits. With a very high number of sequence variants, a naïve multiple hypothesis threshold correction hinders the identification of reliable associations by the overreduction of statistical power. In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic associations. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being performed in whole genome association project by the use of an extreme value distribution and a set of phenotype simulations. Given the familiar nature of the GAW19 data and the finite number of pedigree founders in the sample, the number of correlations between genotypes is greater than in a set of unrelated samples. Using our procedure, we estimate that the effective number represents only 15 % of the total number of independent tests performed. However, even using this corrected significance threshold, no genome-wide significant association could be detected for systolic and diastolic blood pressure traits. The second approach implements a biological relevance-driven hypothesis tested by exploiting prior computational predictions on the effect of nonsynonymous genetic variants detected in a whole genome sequencing association study. This guided testing approach was able to identify 2 promising single-nucleotide polymorphisms (SNPs), 1 for each trait, targeting biologically relevant genes that could help shed light on the genesis of the human hypertension. The first gene, PFH14, associated with systolic blood pressure, interacts directly with genes involved in calcium-channel formation and the second gene, MAP4, encodes a microtubule-associated protein and had already been detected by previous genome-wide association study experiments conducted in an Asian population. Our results highlight the necessity of the development of alternative approached to improve the efficiency on the detection of reasonable candidate associations in whole genome sequencing studies.http://deepblue.lib.umich.edu/bitstream/2027.42/134747/1/12919_2016_Article_38.pd
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