13q32.1 as a candidate region for physiological anisocoria

ABSTRACT Background. Physiological anisocoria is an asymmetry of pupil size in the absence of pathology. Methods. Images of the pupils under standard illumination were collected in the course of a whole-genome association study of a range of visual functions in 1060 healthy adults. DNA for each participant was extracted from saliva samples. Results. We found no relationship between anisocoria and the difference in refraction between the eyes, nor between anisocoria and difference in acuity. There was a small but significant relationship with lightness of the iris, in that the eye with the smaller pupil was associated with the lighter iris. There was a strong association between anisocoria and a local region of chromosome 13 (13q32.1), a region lying between the genes GPR180 and SOX21. The strongest association was with the single nucleotide polymorphism rs9524583. Conclusion. The very specific region associated with anisocoria is one where microdeletions (or microduplications) are known to lead to abnormal development of pupil dilator muscle and hence to the autosomal dominant condition of microcoria. It is possible that alterations at 13q32.1 act by altering the expression of SOX21, which encodes a nuclear transcription factor.Gatsby Charitable Foundation Gonville and Caius Colleg

Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance.

Retinal ganglion cells (RGCs) are the bridging neurons that connect the retinal input to the visual processing centres within the central nervous system. There is a remarkable diversity of RGCs and the various subtypes have unique morphological features, distinct functions, and characteristic pathways linking the inner retina to the relevant brain areas. A number of psychophysical and electrophysiological tests have been refined to investigate this large and varied population of RGCs. Technological advances, such as high-resolution optical coherence tomography imaging, have provided additional tools to define the pattern of RGC involvement and the chronological sequence of events in both inherited and acquired optic neuropathies. The mechanistic insights gained from these studies, in particular the selective vulnerability and relative resilience of particular RGC subtypes, are of fundamental importance as they are directly relevant to the development of targeted therapies for these invariably progressive blinding diseases. This review provides a comprehensive description of the various types of RGCs, the developments in proposed methods of classification, and the current gaps in our knowledge of how these RGCs are differentially affected depending on the underlying aetiology. The synthesis of the current body of knowledge on the diversity of RGCs and the pathways that are potentially amenable to therapeutic modulation will hopefully lead to much needed effective treatments for patients with optic neuropathies

An online version of the Mooney Face Test: phenotypic and genetic associations.

The Mooney Face Test is a widely used test of face perception, but was originally designed to be administered by personal interview. We have developed a three-alternative forced-choice version for online testing. We tested 397 healthy adults between the ages of 18 and 42 (M=24 years). There was a wide range of performance (64-100% correct; M=89.6%). We observed a significant sex difference favoring males (.31 standard deviation; p =.004). In addition, independently of sex, higher 2D:4D digit ratios were significantly associated with higher scores (ρ=.14, p=.006). A genome-wide association study (GWAS) for a subset of 370 participants identified an association between Mooney performance and a polymorphism in the RAPGEF5 gene (rs1522280; p=9.68×10(-8)). This association survives a permutation test (p=.031).This is the author's accepted manuscript. The final version of this paper is published by Elsevier in Neuropsychologia here: http://www.sciencedirect.com/science/article/pii/S0028393214002747

The Oxytocin Receptor Gene ( OXTR) and Face Recognition.

A recent study has linked individual differences in face recognition to rs237887, a single-nucleotide polymorphism (SNP) of the oxytocin receptor gene ( OXTR; Skuse et al., 2014). In that study, participants were assessed using the Warrington Recognition Memory Test for Faces, but performance on Warrington's test has been shown not to rely purely on face recognition processes. We administered the widely used Cambridge Face Memory Test-a purer test of face recognition-to 370 participants. Performance was not significantly associated with rs237887, with 16 other SNPs of OXTR that we genotyped, or with a further 75 imputed SNPs. We also administered three other tests of face processing (the Mooney Face Test, the Glasgow Face Matching Test, and the Composite Face Test), but performance was never significantly associated with rs237887 or with any of the other genotyped or imputed SNPs, after corrections for multiple testing. In addition, we found no associations between OXTR and Autism-Spectrum Quotient scores.This work was supported by Gatsby Charitable Foundation Grant GAT2903

Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial

BACKGROUND: The CELESTIAL trial (NCT01908426) demonstrated overall survival benefit for cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (aHCC) who had received prior sorafenib treatment. This analysis of CELESTIAL compared the impact of cabozantinib versus placebo on health-related quality of life (HRQoL). MATERIALS AND METHODS: Health status was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire over the 800-day follow-up period. EQ-5D-5L health states were mapped to health utility scores using reference values for the UK population. Quality-adjusted life years (QALYs) were calculated for each treatment group as the area under the curve for the plot of health utility score over time. The between-treatment group difference in restricted mean QALYs was calculated by generalized linear models and adjusted for baseline differences. A difference of 0.08 in health utility score (or in QALY) was deemed a minimally important difference and to be clinically significant. RESULTS: At week 5, the difference in mean health utility score between cabozantinib and placebo was -0.097 (95% confidence interval [95% CI]: -0.126, -0.067; p ≤ 0.001). Between-group differences in health utility scores diminished over time and were generally non-significant. The cabozantinib group accrued more QALYs than the placebo group over follow-up. Differences in mean QALYs (cabozantinib minus placebo) were statistically and clinically significant, ranging from +0.092 (95% CI: 0.016, 0.169) to +0.185 (95% CI: 0.126, 0.243) in favour of cabozantinib, depending on the reference value set used. CONCLUSIONS: These HRQoL findings support a positive benefit-risk profile for cabozantinib in previously treated patients with aHCC

General and specific factors in the processing of faces.

The ability to recognize faces varies considerably between individuals, but does performance co-vary for tests of different aspects of face processing? For 397 participants (of whom the majority were university students) we obtained scores on the Mooney Face Test, Glasgow Face Matching Test (GFMT), Cambridge Face Memory Test (CFMT) and Composite Face Test. Overall performance was significantly correlated for each pair of tests, and we suggest the term f for the factor underlying this pattern of positive correlations. However, there were large variations in the amount of variance shared by individual tests: The GFMT and CFMT are strongly related, whereas the GFMT and the Mooney test tap largely independent abilities. We do not replicate a frequently reported relationship between holistic processing (from the Composite test) and face recognition (from the CFMT)-indeed, holistic processing does not correlate with any of our tests. We report associations of performance with digit ratio and autism-spectrum quotient (AQ), and from our genome-wide association study we include a list of suggestive genetic associations with performance on the four face tests, as well as with f.Gatsby Charitable Foundation (Grant ID: GAT2903

The oxytocin receptor gene OXTR is not associated with face recognition

A recent study has linked individual differences in face recognition to rs237887, a single-nucleotide polymorphism (SNP) of the oxytocin receptor gene (OXTR; Skuse et al., 2014). In that study, participants were assessed using the Warrington Recognition Memory Test for Faces, but performance on Warrington’s test has been shown not to rely purely on face recognition processes. We administered the widely used Cambridge Face Memory Test—a purer test of face recognition—to 370 participants. Performance was not significantly associated with rs237887, with 16 other SNPs of OXTR that we genotyped, or with a further 75 imputed SNPs. We also administered three other tests of face processing (the Mooney Face Test, the Glasgow Face Matching Test, and the Composite Face Test), but performance was never significantly associated with rs237887 or with any of the other genotyped or imputed SNPs, after corrections for multiple testing. In addition, we found no associations between OXTR and Autism-Spectrum Quotient scores

Storage Resource Manager version 2.2: design, implementation, and testing experience

Storage Services are crucial components of the Worldwide LHC Computing Grid Infrastructure spanning more than 200 sites and serving computing and storage resources to the High Energy Physics LHC communities. Up to tens of Petabytes of data are collected every year by the four LHC experiments at CERN. To process these large data volumes it is important to establish a protocol and a very efficient interface to the various storage solutions adopted by the WLCG sites. In this work we report on the experience acquired during the definition of the Storage Resource Manager v2.2 protocol. In particular, we focus on the study performed to enhance the interface and make it suitable for use by the WLCG communities. At the moment 5 different storage solutions implement the SRM v2.2 interface: BeStMan (LBNL), CASTOR (CERN and RAL), dCache (DESY and FNAL), DPM (CERN), and StoRM (INFN and ICTP). After a detailed inside review of the protocol, various test suites have been written identifying the most effective set of tests: the S2 test suite from CERN and the SRM-Tester test suite from LBNL. Such test suites have helped verifying the consistency and coherence of the proposed protocol and validating existing implementations. We conclude our work describing the results achieved

Effects of automated alerts on unnecessarily repeated serology tests in a cardiovascular surgery department: a time series analysis

<p>Abstract</p> <p>Background</p> <p>Laboratory testing is frequently unnecessary, particularly repetitive testing. Among the interventions proposed to reduce unnecessary testing, Computerized Decision Support Systems (CDSS) have been shown to be effective, but their impact depends on their technical characteristics. The objective of the study was to evaluate the impact of a Serology-CDSS providing point of care reminders of previous existing serology results, embedded in a Computerized Physician Order Entry at a university teaching hospital in Paris, France.</p> <p>Methods</p> <p>A CDSS was implemented in the Cardiovascular Surgery department of the hospital in order to decrease inappropriate repetitions of viral serology tests (HBV).</p> <p>A time series analysis was performed to assess the impact of the alert on physicians' practices. The study took place between January 2004 and December 2007. The primary outcome was the proportion of unnecessarily repeated HBs antigen tests over the periods of the study. A test was considered unnecessary when it was ordered within 90 days after a previous test for the same patient. A secondary outcome was the proportion of potentially unnecessary HBs antigen test orders cancelled after an alert display.</p> <p>Results</p> <p>In the pre-intervention period, 3,480 viral serology tests were ordered, of which 538 (15.5%) were unnecessarily repeated. During the intervention period, of the 2,095 HBs antigen tests performed, 330 unnecessary repetitions (15.8%) were observed. Before the intervention, the mean proportion of unnecessarily repeated HBs antigen tests increased by 0.4% per month (absolute increase, 95% CI 0.2% to 0.6%, <it>p </it>< 0.001). After the intervention, a significant trend change occurred, with a monthly difference estimated at -0.4% (95% CI -0.7% to -0.1%, <it>p </it>= 0.02) resulting in a stable proportion of unnecessarily repeated HBs antigen tests. A total of 380 unnecessary tests were ordered among 500 alerts displayed (compliance rate 24%).</p> <p>Conclusions</p> <p>The proportion of unnecessarily repeated tests immediately dropped after CDSS implementation and remained stable, contrasting with the significant continuous increase observed before. The compliance rate confirmed the effect of the alerts. It is necessary to continue experimentation with dedicated systems in order to improve understanding of the diversity of CDSS and their impact on clinical practice.</p