Rule knowledge aids performance on spatial and object alternation tasks by alcoholic patients with and without Korsakoff’s amnesia

Delayed alternation (DA) and object alternation (OA) tasks traditionally have been used to measure defective response inhibition associated with dysfunction of frontal brain systems. However, these tasks are also sensitive to nonfrontal lesions, and cognitive processes such as the induction of rule-learning strategies also are needed in order to perform well on these tasks. Performance on DA and OA tasks was explored in 10 patients with alcohol-induced persisting amnestic disorder (Korsakoff’s syndrome), 11 abstinent long-term alcoholics, and 13 healthy non-alcoholic controls under each of two rule provision conditions: Alternation Rule and Correction Rule. Results confirmed that rule knowledge is a crucial cognitive component for solving problems such as DA and OA, and therefore, that errors on these tasks are not due to defective response inhibition alone. Further, rule-induction strategies were helpful to Korsakoff patients, despite their poorer performance on the tasks. These results stress the role of multiple cognitive abilities in successful performance on rule induction tasks. Evidence that these cognitive abilities are served by diffusely distributed neural networks should be considered when interpreting behavioral impairments on these tasks

Asphaltene detection using Surface Enhanced Raman Scattering (SERS)

Peer reviewedPostprin

Survival of Organic Materials in Hypervelocity Impacts of Ice on Sand, Ice, and Water in the Laboratory

The survival of organic molecules in shock impact events has been investigated in the laboratory. A frozen mixture of anthracene and stearic acid, solvated in dimethylsulfoxide (DMSO), was fired in a two-stage light gas gun at speeds of ?2 and ?4?km s?1 at targets that included water ice, water, and sand. This involved shock pressures in the range of 2–12 GPa. It was found that the projectile materials were present in elevated quantities in the targets after impact and in some cases in the crater ejecta as well. For DMSO impacting water at 1.9?km s?1 and 45° incidence, we quantify the surviving fraction after impact as 0.44±0.05. This demonstrates successful transfer of organic compounds from projectile to target in high-speed impacts. The range of impact speeds used covers that involved in impacts of terrestrial meteorites on the Moon, as well as impacts in the outer Solar System on icy bodies such as Pluto. The results provide laboratory evidence that suggests that exogenous delivery of complex organic molecules from icy impactors is a viable source of such material on target bodies

Rhinal cortex asymmetries in patients with mesial temporal sclerosis

SummaryPurposeThe rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices, is one component of the limbic system that may be affected in patients with epilepsy and other temporal lobe pathologies. This study extended quantitative examination of the limbic system through development and validation of volumetric protocols to measure the ErC and PrC.MethodsVolumes were calculated from MRI studies using ANALYZE 7.5 and based on detailed anatomical definitions developed for the study. Subjects were 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS: 33 left, 28 right) and 20 neurologically normal controls. Inter-rater reliabilities for the ErC and PrC volume protocols were found to be high (range 0.86–0.92).ResultsIpsilateral hippocampal volume was reduced in patients with MTS, while contralateral volume did not differ significantly from controls. In the patients, rhinal cortex volumes were reduced as a function of laterality of disease. The pattern of correlations between ErC and PrC differed between disease groups. Hippocampal and rhinal cortex volumes were not significantly correlated. A significant four-way interaction was found between side of MTS, hemisphere, structure and handedness.ConclusionsThis quantitative study demonstrates reliable in vivo evidence of morphometric changes in ErC and PrC in a substantial number of patients with unilateral MTS. The relationship observed between handedness, structure and disease status may suggest a role for cerebral dominance in modulating the expression of MTS

Genomic tools reveal complex social organization of an invasive large mammal (\u3ci\u3eSus scrofa\u3c/i\u3e)

A comprehensive understanding of sociality in wildlife is vital to optimizing conservation and management efforts. However, sociality is complicated, especially for widely distributed species that exhibit substantive behavioral plasticity. Invasive wild pigs (Sus scrofa), often representing hybrids of European wild boar and domestic pigs, are among the most adaptable and widely distributed large mammals. The social structure of wild pigs is believed to be similar to European wild boar, consisting of matriarchal groups (sounders) and solitary males. However, wild pig social structure is understudied and largely limited to visual observations. Using a hierarchical approach, we incorporated genomic tools to describe wild pig social group composition in two disparate ecoregions within their invaded range in North America. The most common social unit was sounders, which are characterized as the association of two or more breeding-aged wild pigs with or without dependent offspring. In addition to sounders, pseudo-solitary females and male-dominated bachelor groups were observed at a greater frequency than previously reported. Though primarily composed of close female kin, some sounders included unrelated females. Bachelor groups were predominantly composed of young, dispersal-aged males and almost always included only close kin. Collectively, our study suggests social organization of wild pigs in their invaded range is similar to that observed among wild boar but is complex, dynamic, and likely variable across invaded habitats

Best (but oft-forgotten) practices:the design, analysis, and interpretation of Mendelian randomization studies

Mendelian randomization (MR) is an increasingly important tool for appraising causality in observational epidemiology. The technique exploits the principle that genotypes are not generally susceptible to reverse causation bias and confounding, reflecting their fixed nature and Mendel’s first and second laws of inheritance. The approach is, however, subject to important limitations and assumptions that, if unaddressed or compounded by poor study design, can lead to erroneous conclusions. Nevertheless, the advent of 2-sample approaches (in which exposure and outcome are measured in separate samples) and the increasing availability of open-access data from large consortia of genome-wide association studies and population biobanks mean that the approach is likely to become routine practice in evidence synthesis and causal inference research. In this article we provide an overview of the design, analysis, and interpretation of MR studies, with a special emphasis on assumptions and limitations. We also consider different analytic strategies for strengthening causal inference. Although impossible to prove causality with any single approach, MR is a highly cost-effective strategy for prioritizing intervention targets for disease prevention and for strengthening the evidence base for public health policy

BMI as a Modifiable Risk Factor for Type 2 Diabetes: Refining and Understanding Causal Estimates Using Mendelian Randomization.

This study focused on resolving the relationship between BMI and type 2 diabetes. The availability of multiple variants associated with BMI offers a new chance to resolve the true causal effect of BMI on type 2 diabetes; however, the properties of these associations and their validity as genetic instruments need to be considered alongside established and new methods for undertaking Mendelian randomization (MR). We explore the potential for pleiotropic genetic variants to generate bias, revise existing estimates, and illustrate value in new analysis methods. A two-sample MR approach with 96 genetic variants was used with three different analysis methods, two of which (MR-Egger and the weighted median) have been developed specifically to address problems of invalid instrumental variables. We estimate an odds ratio for type 2 diabetes per unit increase in BMI (kg/m(2)) of between 1.19 and 1.38, with the most stable estimate using all instruments and a weighted median approach (1.26 [95% CI 1.17, 1.34]). TCF7L2(rs7903146) was identified as a complex effect or pleiotropic instrument, and removal of this variant resulted in convergence of causal effect estimates from different causal analysis methods. This indicated the potential for pleiotropy to affect estimates and differences in performance of alternative analytical methods. In a real type 2 diabetes-focused example, this study demonstrates the potential impact of invalid instruments on causal effect estimates and the potential for new approaches to mitigate the bias caused.Medical Research Council (Grant IDs: MC_UU_12013/1, MC_UU_12013/2, MC_UU_12013/3); University of Bristol; Wellcome Trust (Grant ID: 100114); Medical Research Council (Methodology Research Fellowship, Grant ID: MR/N501906/1); Cancer Research UK (C18281/A19169).This is the author accepted manuscript. The final version is available from American Diabetes Association via http://dx.doi.org/10.2337/db16-041

Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator.

Developments in genome-wide association studies and the increasing availability of summary genetic association data have made application of Mendelian randomization relatively straightforward. However, obtaining reliable results from a Mendelian randomization investigation remains problematic, as the conventional inverse-variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables. We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation analysis, it is shown to have better finite-sample Type 1 error rates than the inverse-variance weighted method, and is complementary to the recently proposed MR-Egger (Mendelian randomization-Egger) regression method. In analyses of the causal effects of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol on coronary artery disease risk, the inverse-variance weighted method suggests a causal effect of both lipid fractions, whereas the weighted median and MR-Egger regression methods suggest a null effect of high-density lipoprotein cholesterol that corresponds with the experimental evidence. Both median-based and MR-Egger regression methods should be considered as sensitivity analyses for Mendelian randomization investigations with multiple genetic variants.Jack Bowden is supported by a Methodology Research Fellowship from the Medical Research Council (grant number MR/N501906/1). George Davey Smith is supported by the Medical Research Council (grant number MC UU 12013/1- 9). Philip C Haycock is supported by a Cancer Research UK Population Research Postdoctoral Fellowship. Stephen Burgess is supported by a fellowship from the Wellcome Trust (100114).This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/gepi.2196

Development and psychometric validation of the mental health-related barriers and benefits to EXercise (MEX) scale in healthy adults

Background: Physical exercise has been shown to reduce anxiety and depression symptoms, the most common mental health disorders globally. Despite the benefits of exercise in anxiety and depression, the symptoms of these disorders may directly contribute to a lack of engagement with exercise. However, mental health-related barriers and benefits to exercise engagement have not been addressed in quantitative research. We introduce the development and psychometric validation of the Mental health-related barriers and benefits to EXercise (MEX) scale. Methods: Three samples were collected online prospectively (sample 1 n = 492; sample 2 n = 302; sample 3 n = 303) for scale refinement and validation with exploratory and confirmatory factor analysis. All participants were generally healthy adults, aged 18–45, and had no history of severe mental illness requiring hospitalization and no physical disability impacting over 50% of daily function. Results: We identified a 30-item, two-factor model comprising 15 barrier and 15 benefit items. Overall model fit was excellent for an item-level scale across the three samples (Comparative Fit Index = 0.935–0.951; Root-Mean-Square Error of Approximation = 0.037–0.039). Internal consistency was also excellent across the three samples (α = 0.900–0.951). The barriers subscale was positively correlated with symptoms of anxiety, depression and stress, and negatively correlated with measures of physical activity and exercise engagement. The benefits subscale was negatively correlated with symptoms of anxiety, depression and stress, and positively correlated with measures of physical activity and exercise engagement. Conclusion: The MEX is a novel, psychometrically robust scale, which is appropriate for research and for clinical use to ascertain individual and/or group level mental health-related barriers and benefits to exercise

Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study

Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic (n = 828) and nondiabetic (n = 170) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease