Visual, Motor and Attentional Influences on Proprioceptive Contributions to Perception of Hand Path Rectilinearity during Reaching

We examined how proprioceptive contributions to perception of hand path straightness are influenced by visual, motor and attentional sources of performance variability during horizontal planar reaching. Subjects held the handle of a robot that constrained goal-directed movements of the hand to the paths of controlled curvature. Subjects attempted to detect the presence of hand path curvature during both active (subject driven) and passive (robot driven) movements that either required active muscle force production or not. Subjects were less able to discriminate curved from straight paths when actively reaching for a target versus when the robot moved their hand through the same curved paths. This effect was especially evident during robot-driven movements requiring concurrent activation of lengthening but not shortening muscles. Subjects were less likely to report curvature and were more variable in reporting when movements appeared straight in a novel “visual channel” condition previously shown to block adaptive updating of motor commands in response to deviations from a straight-line hand path. Similarly, compromised performance was obtained when subjects simultaneously performed a distracting secondary task (key pressing with the contralateral hand). The effects compounded when these last two treatments were combined. It is concluded that environmental, intrinsic and attentional factors all impact the ability to detect deviations from a rectilinear hand path during goal-directed movement by decreasing proprioceptive contributions to limb state estimation. In contrast, response variability increased only in experimental conditions thought to impose additional attentional demands on the observer. Implications of these results for perception and other sensorimotor behaviors are discussed

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Diagnosis and management of spinal muscular atrophy : Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achieve these recommendations, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management. Pulmonary management, acute care, other organ involvement, ethical issues, medications, and the impact of new treatments for SMA are discussed in part 2

Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma

© 2021 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/Purpose: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. Methods: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. Results: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. Conclusion: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.info:eu-repo/semantics/publishedVersio

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1

Muon (g-2) Technical Design Report

The Muon (g-2) Experiment, E989 at Fermilab, will measure the muon anomalous magnetic moment a factor-of-four more precisely than was done in E821 at the Brookhaven National Laboratory AGS. The E821 result appears to be greater than the Standard-Model prediction by more than three standard deviations. When combined with expected improvement in the Standard-Model hadronic contributions, E989 should be able to determine definitively whether or not the E821 result is evidence for physics beyond the Standard Model. After a review of the physics motivation and the basic technique, which will use the muon storage ring built at BNL and now relocated to Fermilab, the design of the new experiment is presented. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2/3 approval

The NANOGrav 15-year Data Set: Evidence for a Gravitational-Wave Background

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15-year pulsar-timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings-Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law-spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of $10^{14}$, and this same model is favored over an uncorrelated common power-law-spectrum model with Bayes factors of 200-1000, depending on spectral modeling choices. We have built a statistical background distribution for these latter Bayes factors using a method that removes inter-pulsar correlations from our data set, finding $p = 10^{-3}$ (approx. $3\sigma$) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of inter-pulsar correlations yields $p = 5 \times 10^{-5} - 1.9 \times 10^{-4}$ (approx. $3.5 - 4\sigma$). Assuming a fiducial $f^{-2/3}$ characteristic-strain spectrum, as appropriate for an ensemble of binary supermassive black-hole inspirals, the strain amplitude is $2.4^{+0.7}_{-0.6} \times 10^{-15}$ (median + 90% credible interval) at a reference frequency of 1/(1 yr). The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black-hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings-Downs correlations points to the gravitational-wave origin of this signal.Comment: 30 pages, 18 figures. Published in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD