Connecting Through Summer Camp: Youth with Visual Impairments Find a Sense of Community

The social meaning of a one-week residential summer sports camp to young people with visual impairments is described. The experiences of 13 youths (7 females and 6 males) with visual impairments (3 B1, 1 B2, and 9 B3) between 9 and 15 years of age were gathered using the phenomenological methods of focus groups, conversational interviews, and field notes. The thematic analysis revealed three themes: connected, reaching out, and resisting and acquiescing. Experiences of group membership and shared emotional connection to others with visual impairments surfaced in a supportive sport context although resistance to others\u27 assumptions of ability was evident. The theory of psychological sense of community (McMillan & Chivas, 1986) provided the conceptual framework for interpreting the findings

Molecular and Clinical Analyses of Greig Cephalopolysyndactyly and Pallister-Hall Syndromes: Robust Phenotype Prediction from the Type and Position of GLI3 Mutations

Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations (among 60 probands); when these were combined with previously published mutations, two genotype-phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/nonsense and splicing mutations. Second, among the frameshift/nonsense mutations, there was a clear genotype-phenotype correlation. Mutations in the first third of the gene (from open reading frame [ORF] nucleotides [nt] 1-1997) caused GCPS, and mutations in the second third of the gene (from ORF nt 1998-3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3\u27 third of the gene (after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis

Transcriptomic analysis of autistic brain reveals convergent molecular pathology.

Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder

Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations

A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial-digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria

Relationship between sociodemographic factors and specialty destination of UK trainee doctors:a national cohort study

We are grateful to UKMED for releasing the data for this project. We also are grateful to the following for their support of the application to UKMED for this and other research projects: Dr Sally Curtis (University of Southampton, UK), Dr Sandra Nicholson (Barts and The London School of Medicine and Dentistry, UK). We thank Daniel Smith and Andy Knapton of the General Medical Council of the UK for their support for the application and throughout the project, particularly regarding data linkage and troubleshooting.Peer reviewedPublisher PD

Exploring Halo Substructure with Giant Stars. XV. Discovery of a Connection between the Monoceros Ring and the Triangulum-Andromeda Overdensity?

Thanks to modern sky surveys, over twenty stellar streams and overdensity structures have been discovered in the halo of the Milky Way. In this paper, we present an analysis of spectroscopic observations of individual stars from one such structure, "A13", first identified as an overdensity using the M giant catalog from the Two Micron All-Sky Survey. Our spectroscopic observations show that stars identified with A13 have a velocity dispersion of $\lesssim$ 40 $\mathrm{km~s^{-1}}$, implying that it is a genuine coherent structure rather than a chance super-position of random halo stars. From its position on the sky, distance ($\sim$15~kpc heliocentric), and kinematical properties, A13 is likely to be an extension of another low Galactic latitude substructure -- the Galactic Anticenter Stellar Structure (also known as the Monoceros Ring) -- towards smaller Galactic longitude and farther distance. Furthermore, the kinematics of A13 also connect it with another structure in the southern Galactic hemisphere -- the Triangulum-Andromeda overdensity. We discuss these three connected structures within the context of a previously proposed scenario that one or all of these features originate from the disk of the Milky Way.Comment: 12 pages, 9 figures. Accepted for publication in Ap

Enhancing arsenic mitigation in Bangladesh: Findings from institutional, psychological, and technical investigations

As part of a trans-disciplinary research project, a series of surveys and interventions were conducted in different arsenic-affected regions of rural Bangladesh. Surveys of institutional stakeholders identified deep tubewells and piped water systems as the most preferred options, and the same preferences were found in household surveys of populations at risk. Psychological surveys revealed that these two technologies were well-supported by potential users, with self-efficacy and social norms being the principal factors driving behavior change. The principal drawbacks of deep tubewells are that installation costs are too high for most families to own private wells, and that for various socio-cultural-religious reasons, people are not willing to walk long distances to access communal tubewells. In addition, water sector planners have reservations about greater exploitation of the deep aquifer, out of concern for current or future geogenic contamination. Groundwater models and field studies have shown that in the great majority of the affected areas, the risk of arsenic contamination of deep groundwater is small; salinity, iron, and manganese are more likely to pose problems. These constituents can in some cases be avoided by exploiting an intermediate depth aquifer of good chemical quality, which is hydraulically and geochemically separate from the arsenic-contaminated shallow aquifer. Deep tubewells represent a technically sound option throughout much of the arsenic-affected regions, and future mitigation programs should build on and accelerate construction of deep tubewells. Utilization of deep tubewells, however, could be improved by increasing the tubewell density (which requires stronger financial support) to reduce travel times, by considering water quality in a holistic way, and by accompanying tubewell installation with motivational interventions based on psychological factors. By combining findings from technical and social sciences, the efficiency and success of arsenic mitigation in general - and installation of deep tubewells in particular - can be significantly enhanced

3D Printing in Zero-G ISS Technology Demonstration

The National Aeronautics and Space Administration (NASA) has a long term strategy to fabricate components and equipment on-demand for manned missions to the Moon, Mars, and beyond. To support this strategy, NASA and Made in Space, Inc. are developing the 3D Printing In Zero-G payload as a Technology Demonstration for the International Space Station. The 3D Printing In Zero-G experiment will be the first machine to perform 3D printing in space. The greater the distance from Earth and the longer the mission duration, the more difficult resupply becomes; this requires a change from the current spares, maintenance, repair, and hardware design model that has been used on the International Space Station up until now. Given the extension of the ISS Program, which will inevitably result in replacement parts being required, the ISS is an ideal platform to begin changing the current model for resupply and repair to one that is more suitable for all exploration missions. 3D Printing, more formally known as Additive Manufacturing, is the method of building parts/ objects/tools layer-by-layer. The 3D Print experiment will use extrusion-based additive manufacturing, which involves building an object out of plastic deposited by a wire-feed via an extruder head. Parts can be printed from data files loaded on the device at launch, as well as additional files uplinked to the device while on-orbit. The plastic extrusion additive manufacturing process is a low-energy, low-mass solution to many common needs on board the ISS. The 3D Print payload will serve as the ideal first step to proving that process in space. It is unreasonable to expect NASA to launch large blocks of material from which parts or tools can be traditionally machined, and even more unreasonable to fly up specialized manufacturing hardware to perform the entire range of function traditionally machining requires. The technology to produce parts on demand, in space, offers unique design options that are not possible through traditional manufacturing methods while offering cost-effective, high-precision, low-unit on-demand manufacturing. Thus, Additive Manufacturing capabilities are the foundation of an advanced manufacturing in space roadmap

Between crime and colony: Interrogating (im)mobilities aboard the convict ship

Recent literature in carceral geography has attended to the importance of mobilities in interrogating the experience and control of spaces of imprisonment, detention and confinement. Scholars have explored the paradoxical nature of incarcerated experience as individuals oscillate between moments of fixity and motion as they are transported to/from carceral environments. This paper draws upon the convict ship – an example yet to gain attention within these emerging discussions – which is both an exemplar of this paradox and a lens through which to complicate understandings of carceral (im)mobilities. The ship is a space of macro-movement from point A to B, whilst simultaneously a site of apparent confinement for those aboard who are unable to move beyond its physical parameters. Yet, we contend that all manner of mobilities permeate the internal space of the ship. Accordingly, we challenge the binary thinking that separates moments of fixity from motion and explore the constituent parts that shape movement. In paying attention to movements in motion on the ship, we argue that studies of carceral mobility must attend to both methods of moving in the space between points A and B; as micro, embodied and intimate (im)mobilities are also played out within large-scale regimes of movement