CEDNIK: Phenotypic and molecular characterization of an additional patient and review of the literature

Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is implicated in intracellular vesicle fusion. Mutations in the SNAP29 gene have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in SNAP29 on the nondeleted chromosome are linked to similar ichthyotic and neurological phenotypes. Here, the authors report a patient with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome who presented with global developmental delay, polymicrogyria, dysgenesis of the corpus callosum, optic nerve dysplasia, gaze apraxia, and dysmorphic features. He has developed ichthyosis and palmoplantar keratoderma as he has grown. Exome sequencing identified a homozygous nonsense mutation in SNAP29 gene designated as c.85C>T (p.Arg29X). The authors compare the findings in the proband with previously reported cases. The previously unreported mutation in this patient and his phenotype add to the characterization of cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome and the accumulating scientific evidence that implicates synaptic protein dysfunction in various neuroectodermal conditions

Chinook Salmon Adult Abundance Monitoring; Hydroacoustic Assessment of Chinook Salmon Escapement to the Secesh River, Idaho, 2002-2004 Final Report.

Accurate determination of adult salmon spawner abundance is key to the assessment of recovery actions for wild Snake River spring/summer Chinook salmon (Onchorynchus tshawytscha), a species listed as 'threatened' under the Endangered Species Act (ESA). As part of the Bonneville Power Administration Fish and Wildlife Program, the Nez Perce Tribe operates an experimental project in the South Fork of the Salmon River subbasin. The project has involved noninvasive monitoring of Chinook salmon escapement on the Secesh River between 1997 and 2000 and on Lake Creek since 1998. The overall goal of this project is to accurately estimate adult Chinook salmon spawning escapement numbers to the Secesh River and Lake Creek. Using time-lapse underwater video technology in conjunction with their fish counting stations, Nez Perce researchers have successfully collected information on adult Chinook salmon spawner abundance, run timing, and fish-per-redd numbers on Lake Creek since 1998. However, the larger stream environment in the Secesh River prevented successful implementation of the underwater video technique to enumerate adult Chinook salmon abundance. High stream discharge and debris loads in the Secesh caused failure of the temporary fish counting station, preventing coverage of the early migrating portion of the spawning run. Accurate adult abundance information could not be obtained on the Secesh with the underwater video method. Consequently, the Nez Perce Tribe now is evaluating advanced technologies and methodologies for measuring adult Chinook salmon abundance in the Secesh River. In 2003, the use of an acoustic camera for assessing spawner escapement was examined. Pacific Northwest National Laboratory, in a collaborative arrangement with the Nez Perce Tribe, provided the technical expertise to implement the acoustic camera component of the counting station on the Secesh River. This report documents the first year of a proposed three-year study to determine the efficacy of using an acoustic camera to count adult migrant Chinook salmon as they make their way to the spawning grounds on the Secesh River and Lake Creek. A phased approach to applying the acoustic camera was proposed, starting with testing and evaluation in spring 2003, followed by a full implementation in 2004 and 2005. The goal of this effort is to better assess the early run components when water clarity and night visibility preclude the use of optical techniques. A single acoustic camera was used to test the technology for enumerating adult salmon passage at the Secesh River. The acoustic camera was deployed on the Secesh at a site engineered with an artificial substrate to control the river bottom morphometry and the passage channel. The primary goal of the analysis for this first year of deployment was to validate counts of migrant salmon. The validation plan involved covering the area with optical video cameras so that both optical and acoustic camera images of the same viewing region could be acquired simultaneously. A secondary test was contrived after the fish passage was complete using a controlled setting at the Pacific Northwest National Laboratory in Richland, Washington, in which we tested the detectability as a function of turbidity levels. Optical and acoustic camera multiplexed video recordings of adult Chinook salmon were made at the Secesh River fish counting station from August 20 through August 29, 2003. The acoustic camera performed as well as or better than the optical camera at detecting adult Chinook salmon over the 10-day test period. However, the acoustic camera was not perfect; the data reflected adult Chinook salmon detections made by the optical camera that were missed by the acoustic camera. The conditions for counting using the optical camera were near ideal, with shallow clear water and good light penetration. The relative performance of the acoustic camera is expected to be even better than the optical camera in early spring when water clarity and light penetration are limited. Results of the laboratory tests at the Pacific Northwest National Laboratory facility indicated that the detection rate for the acoustic camera system was essentially 100% across all levels of turbidity in the experiments. Overall, the acoustic camera outperformed the optical camera at detecting fish, both in the laboratory tank and at the Secesh River fish counting station. However, the optical camera approach still offers some advantages over the acoustic camera under certain limited circumstances. The primary advantages are better species, gender and condition determination and better separation of debris from fish moving downstream. Using both systems in parallel will provide the most robust and accurate platform for counting fish in the field by exploiting the relative strengths of both systems through the season

Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol.

INTRODUCTION: Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map

High-resolution x-ray telescopes

High-energy astrophysics is a relatively young scientific field, made possible by space-borne telescopes. During the half-century history of x-ray astronomy, the sensitivity of focusing x-ray telescopes-through finer angular resolution and increased effective area-has improved by a factor of a 100 million. This technological advance has enabled numerous exciting discoveries and increasingly detailed study of the high-energy universe-including accreting (stellar-mass and super-massive) black holes, accreting and isolated neutron stars, pulsar-wind nebulae, shocked plasma in supernova remnants, and hot thermal plasma in clusters of galaxies. As the largest structures in the universe, galaxy clusters constitute a unique laboratory for measuring the gravitational effects of dark matter and of dark energy. Here, we review the history of high-resolution x-ray telescopes and highlight some of the scientific results enabled by these telescopes. Next, we describe the planned next-generation x-ray-astronomy facility-the International X-ray Observatory (IXO). We conclude with an overview of a concept for the next next-generation facility-Generation X. The scientific objectives of such a mission will require very large areas (about 10000 m2) of highly-nested lightweight grazing-incidence mirrors with exceptional (about 0.1-arcsecond) angular resolution. Achieving this angular resolution with lightweight mirrors will likely require on-orbit adjustment of alignment and figure.Comment: 19 pages, 11 figures, SPIE Conference 7803 "Adaptive X-ray Optics", part of SPIE Optics+Photonics 2010, San Diego CA, 2010 August 2-

Development of white matter circuitry in infants with fragile x syndrome

IMPORTANCE Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder and the most common inherited cause of intellectual disability in males. However, there are no published data on brain development in children with FXS during infancy. OBJECTIVE To characterize the development of white matter at ages 6, 12, and 24 months in infants with FXS compared with that of typically developing controls. DESIGN, SETTING, AND PARTICIPANTS Longitudinal behavioral and brain imaging datawere collected at 1 or more time points from 27 infants with FXS and 73 typically developing controls between August 1, 2008, and June 14, 2016, at 2 academic medical centers. Infants in the control group had no first- or second-degree relatives with intellectual or psychiatric disorders, including FXS and autism spectrum disorder. MAIN OUTCOMES AND MEASURES Nineteen major white matter pathwayswere defined in common atlas space based on anatomically informed methods. Diffusion parameters, including fractional anisotropy, were compared between groups using linear mixed effects modeling. Fiber pathways showing group differences were subsequently examined in association with direct measures of verbal and nonverbal development. RESULTS There were significant differences in the development of 12 of 19 fiber tracts between the 27 infants with FXS (22 boys and 5 girls) and the 73 infants in the control group (46 boys and 27 girls), with lower fractional anisotropy in bilateral subcortical-frontal, occipital-temporal, temporal-frontal, and cerebellar-thalamic pathways, as well as 4 of 6 subdivisions of the corpus callosum. For all 12 of these pathways, there were significant main effects between groups but not for the interaction of age × group, indicating that lower fractional anisotropy was present and stable from age 6 months in infants with FXS. Lower fractional anisotropy values in the uncinate fasciculi were correlated with lower nonverbal developmental quotient in the FXS group (left uncinate, F = 10.06; false discovery rate-corrected P = .03; right uncinate, F = 21.8; P = .004). CONCLUSIONS AND RELEVANCE The results substantiate in human infants the essential role of fragile X gene expression in the early development of white matter. The findings also suggest that the neurodevelopmental effects of FXS are well established at 6 months of age

Development of cortical shape in the human brain from 6 to 24months of age via a novel measure of shape complexity

The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the ‘shape complexity index’ (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of secondary and tertiary sulci. Current cortical shape measures, such as the gyrification index (GI) or intrinsic curvature measures, investigate the cortical surface at a different scale and are less well suited to capture these particular cortical surface changes. In our experiments, the proposed SCI demonstrates higher complexity in the gyral/sulcal wall regions, lower complexity in wider gyral ridges and lowest complexity in wider sulcal fundus regions. In early postnatal brain development, our experiments show that SCI reveals a pattern of increased cortical shape complexity with age, as well as sexual dimorphisms in the insula, middle cingulate, parieto-occipital sulcal and Broca's regions. Overall, sex differences were greatest at 6 months of age and were reduced at 24 months, with the difference pattern switching from higher complexity in males at 6 months to higher complexity in females at 24months. This is the first study of longitudinal, cortical complexity maturation and sex differences, in the early postnatal period from 6 to 24 months of age with fine scale, cortical shape measures. These results provide information that complement previous studies of gyrification index in early brain development

Pathway to the PiezoElectronic Transduction Logic Device

The information age challenges computer technology to process an exponentially increasing computational load on a limited energy budget - a requirement that demands an exponential reduction in energy per operation. In digital logic circuits, the switching energy of present FET devices is intimately connected with the switching voltage, and can no longer be lowered sufficiently, limiting the ability of current technology to address the challenge. Quantum computing offers a leap forward in capability, but a clear advantage requires algorithms presently developed for only a small set of applications. Therefore, a new, general purpose, classical technology based on a different paradigm is needed to meet the ever increasing demand for data processing.Comment: in Nano Letters (2015

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area