Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically

The central image of a gravitationally lensed quasar

A galaxy can act as a gravitational lens, producing multiple images of a background object. Theory predicts there should be an odd number of images but, paradoxically, almost all observed lenses have 2 or 4 images. The missing image should be faint and appear near the galaxy's center. These ``central images'' have long been sought as probes of galactic cores too distant to resolve with ordinary observations. There are five candidates, but in one case the third image is not necessarily a central image, and in the others, the central component might be a foreground source rather than a lensed image. Here we report the most secure identification of a central image, based on radio observations of PMN J1632-0033, one of the latter candidates. Lens models incorporating the central image show that the mass of the lens galaxy's central black hole is less than 2 x 10^8 M_sun, and the galaxy's surface density at the location of the central image is more than 20,000 M_sun per square parsec, in agreement with expectations based on observations of galaxies hundreds of times closer to the Earth.Comment: Nature, in press [7 pp, 2 figs]. Standard media embargo applies before publicatio

An eclipsing binary distance to the Large Magellanic Cloud accurate to 2 per cent

In the era of precision cosmology it is essential to determine the Hubble Constant with an accuracy of 3% or better. Currently, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC) which as the second nearest galaxy serves as the best anchor point of the cosmic distance scale. Observations of eclipsing binaries offer a unique opportunity to precisely and accurately measure stellar parameters and distances. The eclipsing binary method was previously applied to the LMC but the accuracy of the distance results was hampered by the need to model the bright, early-type systems used in these studies. Here, we present distance determinations to eight long-period, late- type eclipsing systems in the LMC composed of cool giant stars. For such systems we can accurately measure both the linear and angular sizes of their components and avoid the most important problems related to the hot early-type systems. Our LMC distance derived from these systems is demonstrably accurate to 2.2 % (49.97 +/- 0.19 (statistical) +/- 1.11 (systematic) kpc) providing a firm base for a 3 % determination of the Hubble Constant, with prospects for improvement to 2 % in the future.Comment: 34 pages, 5 figures, 13 tables, published in the Nature, a part of our data comes from new unpublished OGLE-IV photometric dat

The virtual haptic back: A simulation for training in palpatory diagnosis

<p>Abstract</p> <p>Background</p> <p>Models and simulations are finding increased roles in medical education. The Virtual Haptic Back (VHB) is a virtual reality simulation of the mechanical properties of the human back designed as an aid to teaching clinical palpatory diagnosis.</p> <p>Methods</p> <p>Eighty-nine first year medical students of the Ohio University College of Osteopathic Medicine carried out six, 15-minute practice sessions with the VHB, plus tests before and after the sessions in order to monitor progress in identifying regions of simulated abnormal tissue compliance. Students palpated with two digits, fingers or thumbs, by placing them in gimbaled thimbles at the ends of PHANToM 3.0^®haptic interface arms. The interface simulated the contours and compliance of the back surface by the action of electric motors. The motors limited the compression of the virtual tissues induced by the palpating fingers, by generating counterforces. Users could see the position of their fingers with respect to the back on a video monitor just behind the plane of the haptic back. The abnormal region varied randomly among 12 locations between trials. During the practice sessions student users received immediate feedback following each trial, indicating either a correct choice or the actual location of the abnormality if an incorrect choice had been made. This allowed the user to feel the actual abnormality before going on to the next trial. Changes in accuracy, speed and Weber fraction across practice sessions were analyzed using a repeated measures analysis of variance.</p> <p>Results</p> <p>Students improved in accuracy and speed of diagnosis with practice. The smallest difference in simulated tissue compliance users were able to detect improved from 28% (SD = 9.5%) to 14% (SD = 4.4%) during the practice sessions while average detection time decreased from 39 (SD = 19.8) to 17 (SD = 11.7) seconds. When asked in anonymous evaluation questionnaires if they judged the VHB practice to be helpful to them in the clinical palpation and manual medicine laboratory, 41% said yes, 51% said maybe, and 8% said no.</p> <p>Conclusion</p> <p>The VHB has potential value as a teaching aid for students in the initial phases of learning palpatory diagnosis.</p

The Distances of the Magellanic Clouds

The present status of our knowledge of the distances to the Magellanic Clouds is evaluated from a post-Hipparcos perspective. After a brief summary of the effects of structure, reddening, age and metallicity, the primary distance indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring, Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived via these methods are weighted and combined to produce final "best" estimates for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in pres

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Resident interest and factors involved in entering a pediatric pulmonary fellowship

BACKGROUND: Relatively little is known about interest in pediatric pulmonology among pediatric residents. The purpose of this study, therefore, was to determine at this institution: 1) the level of pediatric resident interest in pursuing a pulmonary fellowship, 2) potential factors involved in development of such interest, 3) whether the presence of a pulmonary fellowship program affects such interest. METHODS: A questionnaire was distributed to all 52 pediatric residents at this institution in 1992 and to all 59 pediatric residents and 14 combined internal medicine/pediatrics residents in 2002, following development of a pulmonary fellowship program. RESULTS: Response rates were 79% in 1992 and 86% in 2002. Eight of the 43 responders in 1992 (19%) had considered doing a pulmonary fellowship compared to 7 of 63 (11%) in 2002. The highest ranked factors given by the residents who had considered a fellowship included wanting to continue one's education after residency, enjoying caring for pulmonary patients, and liking pulmonary physiology and the pulmonary faculty. Major factors listed by residents who had not considered a pulmonary fellowship included not enjoying the tracheostomy/ventilator population and chronic pulmonary patients in general, and a desire to enter general pediatrics or another fellowship. Most residents during both survey periods believed that they would be in non-academic or academic general pediatrics in 5 years. Only 1 of the 106 responding residents (~1%) anticipated becoming a pediatric pulmonologist. CONCLUSIONS: Although many pediatric residents consider enrolling in a pulmonary fellowship (~10–20% here), few (~1% here) will actually pursue a career in pediatric pulmonology. The presence of a pulmonary fellowship program did not significantly alter resident interest, though other confounding factors may be involved

Type 2 diabetes, socioeconomic status and life expectancy in Scotland (2012-2014):a population-based observational study

Aims/hypothesis: The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. Methods: An observational population-based cohort study was performed using the Scottish Care Information – Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40–89 during the period 2012–2014, and for the remaining population of Scotland aged 40–89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. Results: Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80–89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from −5.5 years (95% CI −6.2, −4.8) for women aged 40–44 in the second most-deprived quintile of SES, to 0.1 years (95% CI −0.2, 0.4) for men aged 85–89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. Conclusions/interpretation: Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups)