An extended set of yeast-based functional assays accurately identifies human disease mutations

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods

Comparison of slot scanning digital mammography system with full-field digital mammography system

The purpose of this study was to evaluate and compare microcalcification detectability of two commercial full-field digital mammography (DM) systems. The first unit was a flat panel based DM system (FFDM) which employed an anti-scatter grid method to reject scatter, and the second unit was a charge-coupled device-based DM system (SSDM) which used scanning slot imaging geometry to reduce scatter radiation. Both systems have comparable scatter-to-primary ratios. In this study, 125–160 and 200–250 μm calcium carbonate grains were used to simulate microcalcifications and imaged by both DM systems. The calcium carbonate grains were overlapped with a 5-cm-thick 50% adipose∕50% glandular simulated breast tissue slab and an anthropomorphic breast phantom (RMI 165, Gammex) for imaging at two different mean glandular dose levels: 0.87 and 1.74 mGy. A reading study was conducted with seven board certified mammographers with images displayed on review workstations. A five-point confidence level rating was used to score each detection task. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (Az) was used to quantify and compare the performances of these two systems. The results showed that with the simulated breast tissue slab (uniform background), the SSDM system resulted in higher Az’s than the FFDM system at both MGD levels with the difference statistically significant at 0.87 mGy only. With the anthropomorphic breast phantom (tissue structure background), the SSDM system performed better than the FFDM system at 0.87 mGy but worse at 1.74 mGy. However, the differences were not found to be statistically significant

Aphasia friendly written health information: Content and design characteristics

People with aphasia need communicatively accessible written health information. Healthcare providers require knowledge of how to develop printed education materials (PEMs) in formats that people with aphasia prefer and can read. This study aimed to explore formatting characteristics considered to be barriers and facilitators to reading PEMs. Semi-structured in-depth interviews were conducted with 40 adults with aphasia who were selected using maximum variation sampling across aphasia severity, reading ability, and time post-stroke. Participants were shown stroke and aphasia PEMs obtained from the recruiting stroke services, asked to rank them from most liked to least liked, and comment on factors that made the PEMs easier and harder to read. The majority of participants ranked the aphasia friendly stroke (56.4%, n = 22) and aphasia (87.2%, n = 34) PEMs as most liked. Forty-five facilitator and 46 barrier codes were identified using qualitative content analysis and grouped into two categories; (1) content characteristics and (2) design characteristics. Findings support many of the recommendations found within the literature for developing best practice PEMs and accessible information for other patient groups. Routine consideration of the facilitators and barriers identified will contribute to making written information more accessible to people with aphasia

Editor-in-Chief Editor-in-Chief JEPonline Increasing Physical Activity Decreases Hepatic Fat and Metabolic Risk Factors

ABSTRACT Alderete TL, Gyllenhammer LE, Byrd-Williams CE, Spruijt-Metz D, Goran MI, Davis JN. Increasing Physical Activity Decreases Hepatic Fat and Metabolic Risk Factors. JEPonline 2012;15(2):40-54. This study assessed the changes in time spent in moderate to vigorous physical activity (MVPA) on fat depots, insulin action, and inflammation. Longitudinal data were generated from 66 Hispanic adolescents (15.6±1.1 yr; BMI percentile 97.1±3.0) who participated in a 16-wk nutrition or nutrition+exercise intervention. There were no effects of the intervention on PA, but there were inter-individual changes in PA. For purposes of this analysis, all intervention groups were combined to assess how changes in PA during 16 wk affected changes in adiposity, insulin action, and markers of inflammation. MVPA was assessed by 7-day accelerometry, total body fat via DXA, liver fat by MRI, and insulin, glucose and HOMA-IR via a fasting blood draw. A repeated measures ANCOVA was used to assess the effect of MVPA on fat depots, insulin action, and inflammatory markers. Sixty-two percent of participants increased MVPA (mean increase, 19.7±16.5 min/day) and 38% decreased MVPA (mean decrease, 10.7±10.1 min/day). Those who increased MVPA by as little as 20 min per day over 16 wk, compared to those who decreased MVPA, had significant reductions in liver fat (-13% vs. +3%; P=0.01), leptin levels (-18% vs. +4%; P=0.02), and fasting insulin (-23% vs. +5%; P=0.05). These findings indicate that a modest increase in MVPA can improve metabolic health in sedentary overweight Hispanic adolescents