Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS

Motivation: Epistasis, the presence of gene–gene interactions, has been hypothesized to be at the root of many common human diseases, but current genome-wide association studies largely ignore its role. Multifactor dimensionality reduction (MDR) is a powerful model-free method for detecting epistatic relationships between genes, but computational costs have made its application to genome-wide data difficult. Graphics processing units (GPUs), the hardware responsible for rendering computer games, are powerful parallel processors. Using GPUs to run MDR on a genome-wide dataset allows for statistically rigorous testing of epistasis

Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations

The presence of two active X chromosomes (XaXa) is a hallmark of the ground state of pluripotency specific to murine embryonic stem cells (ESCs). Human ESCs (hESCs) invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of XaXa hESCs derived under physiological oxygen concentrations. Using these cell lines, we demonstrate that (1) differentiation of hESCs induces random XCI in a manner similar to murine ESCs, (2) chronic exposure to atmospheric oxygen is sufficient to induce irreversible XCI with minor changes of the transcriptome, (3) the Xa exhibits heavy methylation of the XIST promoter region, and (4) XCI is associated with demethylation and transcriptional activation of XIST along with H3K27-me3 deposition across the Xi. These findings indicate that the human blastocyst contains pre-X-inactivation cells and that this state is preserved in vitro through culture under physiological oxygen.Susan WhiteheadHillel and Liliana Bachrac

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Physical length scales of wind-blown snow redistribution and accumulation on relatively smooth Arctic first-year sea ice

Snow thickness measurements over relatively smooth Arctic first-year sea ice, obtained near Cambridge Bay, Nunavut, Canada (2014, 2016 and 2017) and near Elson Lagoon, Alaska, USA (2003 and 2006), are analyzed to quantify physical length-scales and their relevant scaling behaviors. We use the Multi-Fractal Temporally Weighted Detrended Fluctuation Analysis (MF-TWDFA) method to detect two major physical length-scales from both the study areas. Our results suggest that physical processes underlying the formation of snow dunes are consistent and that the wind is the main process shaping the redistribution and variability of snow thickness. One scale, around 10 m, appears to be related to the formation of the snow "dunes", while the other scale, between 30 m and 60 m, is likely associated with the various interactions of the snow dunes including merging, calving and lateral linking showing self-organized characteristics. We suggest that a simple cellular automata model can be used to generate the variability of snow thickness on smooth Arctic first-year sea ice

Distorted Cognitive Processing in Youth: The Structure of Negative Cognitive Errors and Their Associations with Anxiety

The Children’s Negative Cognitive Error Questionnaire (CNCEQ) is commonly used to measure four errors in young people’s thinking, but research has failed to support the factorial validity of the measure. The primary objective of the present study was to examine the factor structure of a refined and extended version of the CNCEQ. Revision of the CNCEQ involved the exclusion of items rated as contaminated, and the addition of items measuring cognitive errors closely associated with anxiety (‘threat conclusion’ and ‘underestimation of the ability to cope’). A secondary objective was to determine the relation between the negative cognitive errors and anxiety. Principal component analysis of data from 481 children and adolescents indicated five distinct negative cognitive error subscales labeled ‘underestimation of the ability to cope’, ‘personalizing without mind reading’, ‘selective abstraction’, ‘overgeneralizing’, and ‘mind reading’ which contained the new ‘threat conclusion’ items. Confirmatory factor analysis in an independent sample of 295 children and adolescents yielded further support for the five-factor solution. All cognitive errors except ‘selective abstraction’ were correlated with anxiety. Multiple regression analysis indicated that the strongest predictors of anxiety were the two subscales containing new items, namely ‘underestimation of the ability to cope’ and ‘mind reading’. The results are discussed with respect to further development of the instrument so as to advance the assessment of distorted cognitive processing in young people with internalizing symptoms

Surface processes recorded by rocks and soils on Meridiani Planum, Mars: Microscopic Imager observations during Opportunity's first three extended missions

The Microscopic Imager (MI) on the Mars Exploration Rover Opportunity has returned images of Mars with higher resolution than any previous camera system, allowing detailed petrographic and sedimentological studies of the rocks and soils at the Meridiani Planum landing site. Designed to simulate a geologist's hand lens, the MI is mounted on Opportunity's instrument arm and can resolve objects 0.1 mm across or larger. This paper provides an overview of MI operations, data calibration, and analysis of MI data returned during the first 900 sols (Mars days) of the Opportunity landed mission. Analyses of Opportunity MI data have helped to resolve major questions about the origin of observed textures and features. These studies support eolian sediment transport, rather than impact surge processes, as the dominant depositional mechanism for Burns formation strata. MI stereo observations of a rock outcrop near the rim of Erebus Crater support the previous interpretation of similar sedimentary structures in Eagle Crater as being formed by surficial flow of liquid water. Well-sorted spherules dominate ripple surfaces on the Meridiani plains, and the size of spherules between ripples decreases by about 1 mm from north to south along Opportunity's traverse between Endurance and Erebus craters

Matrilineal behavioral and physiological changes following the death of a non-alpha matriarch in rhesus macaque

In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. In a retrospective study, we tested that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the removal of a non-alpha matriarch, who had a large set of kin, led to changes in behavior and physiological stress within her matriline. Following her removal, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high-ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch’s removal, following her removal, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the removal of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines.Division of Intramural Research, National Institute of Child Health and Human Development, 1ZIAHD001107- 3

Psychosocial Treatment of Children in Foster Care: A Review

A substantial number of children in foster care exhibit psychiatric difficulties. Recent epidemiologi-cal and historical trends in foster care, clinical findings about the adjustment of children in foster care, and adult outcomes are reviewed, followed by a description of current approaches to treatment and extant empirical support. Available interventions for these children can be categorized as either symptom-focused or systemic, with empirical support for specific methods ranging from scant to substantial. Even with treatment, behavioral and emotional problems often persist into adulthood, resulting in poor functional outcomes. We suggest that self-regulation may be an important mediat-ing factor in the appearance of emotional and behavioral disturbance in these children