Reachable Workspace and Proximal Function Measures for Quantifying Upper Limb Motion.

There are a lack of quantitative measures for clinically assessing upper limb function. Conventional biomechanical performance measures are restricted to specialist labs due to hardware cost and complexity, while the resulting measurements require specialists for analysis. Depth cameras are low cost and portable systems that can track surrogate joint positions. However, these motions may not be biologically consistent, which can result in noisy, inaccurate movements. This paper introduces a rigid body modelling method to enforce biological feasibility of the recovered motions. This method is evaluated on an existing depth camera assessment: the reachable workspace (RW) measure for assessing gross shoulder function. As a rigid body model is used, position estimates of new proximal targets can be added, resulting in a proximal function (PF) measure for assessing a subject's ability to touch specific body landmarks. The accuracy, and repeatability of these measures is assessed on ten asymptomatic subjects, with and without rigid body constraints. This analysis is performed both on a low-cost depth camera system and a gold-standard active motion capture system. The addition of rigid body constraints was found to improve accuracy and concordance of the depth camera system, particularly in lateral reaching movements. Both RW and PF measures were found to be feasible candidates for clinical assessment, with future analysis needed to determine their ability to detect changes within specific patient populations

EEG reinvestigations of visual statistical learning for faces, scenes, and objects

The objective of this ongoing, replication study is to understand temporal and spatial patterns in our environment by using the technique of electroencephalography (EEG). Visual statistical learning (VSL) helps us to understand conditional probabilities from our environments. This concept is why we know that chairs are located under tables, not above. The goal of this study is to understand whether participants can unconsciously associate pairs of items (faces, scenes, and objects) from their short-term memory. Strong pairs become more similar to each other, as compared to weak pairs, which become less similar. In the main task, participants saw items appear on the screen, on at a time, for 100ms each. Items directly followed each other without transitions. In the post-task, participants were asked to rate how familiar pairs of items were, using a sliding scale. There were three types of pairs presented: strong pairs where item B followed item A 100% of the time; weak pairs where item B followed item A 11% of the time; and foil pairs where item B followed item A 0% of the time. In conclusion, results are similar to the current study (n = 10) in that there are behavioral differences between strong vs. foil and strong vs. weak pairs

Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition

Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting. To characterize interactions among the gut microbiota, human milk oligosaccharides (HMOs), and osteoclast and osteoblast biology, young germ-free mice were colonized with cultured bacterial strains from a 6-mo-old stunted infant and fed a diet mimicking that consumed by the donor population. Adding purified bovine sialylated milk oligosaccharides (S-BMO) with structures similar to those in human milk to this diet increased femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses. Comparisons of germ-free and colonized mice revealed S-BMO-dependent and microbiota-dependent increases in cecal levels of succinate, increased numbers of small intestinal tuft cells, and evidence for activation of a succinate-induced tuft cell signaling pathway linked to Th2 immune responses. A prominent fucosylated HMO, 2'-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects. These results underscore the need to further characterize the balance between, and determinants of, osteoclastic and osteoblastic activity in stunted infants/children, and suggest that certain milk oligosaccharides may have therapeutic utility in this setting

Characterizing Signal Loss in the 21 cm Reionization Power Spectrum: A Revised Study of PAPER-64

The Epoch of Reionization (EoR) is an uncharted era in our Universe's history during which the birth of the first stars and galaxies led to the ionization of neutral hydrogen in the intergalactic medium. There are many experiments investigating the EoR by tracing the 21cm line of neutral hydrogen. Because this signal is very faint and difficult to isolate, it is crucial to develop analysis techniques that maximize sensitivity and suppress contaminants in data. It is also imperative to understand the trade-offs between different analysis methods and their effects on power spectrum estimates. Specifically, with a statistical power spectrum detection in HERA's foreseeable future, it has become increasingly important to understand how certain analysis choices can lead to the loss of the EoR signal. In this paper, we focus on signal loss associated with power spectrum estimation. We describe the origin of this loss using both toy models and data taken by the 64-element configuration of the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER). In particular, we highlight how detailed investigations of signal loss have led to a revised, higher 21cm power spectrum upper limit from PAPER-64. Additionally, we summarize errors associated with power spectrum error estimation that were previously unaccounted for. We focus on a subset of PAPER-64 data in this paper; revised power spectrum limits from the PAPER experiment are presented in a forthcoming paper by Kolopanis et al. (in prep.) and supersede results from previously published PAPER analyses.Comment: 25 pages, 18 figures, Accepted by Ap

High-Throughput Precision Phenotyping of Left Ventricular Hypertrophy with Cardiovascular Deep Learning

Left ventricular hypertrophy (LVH) results from chronic remodeling caused by a broad range of systemic and cardiovascular disease including hypertension, aortic stenosis, hypertrophic cardiomyopathy, and cardiac amyloidosis. Early detection and characterization of LVH can significantly impact patient care but is limited by under-recognition of hypertrophy, measurement error and variability, and difficulty differentiating etiologies of LVH. To overcome this challenge, we present EchoNet-LVH - a deep learning workflow that automatically quantifies ventricular hypertrophy with precision equal to human experts and predicts etiology of LVH. Trained on 28,201 echocardiogram videos, our model accurately measures intraventricular wall thickness (mean absolute error [MAE] 1.4mm, 95% CI 1.2-1.5mm), left ventricular diameter (MAE 2.4mm, 95% CI 2.2-2.6mm), and posterior wall thickness (MAE 1.2mm, 95% CI 1.1-1.3mm) and classifies cardiac amyloidosis (area under the curve of 0.83) and hypertrophic cardiomyopathy (AUC 0.98) from other etiologies of LVH. In external datasets from independent domestic and international healthcare systems, EchoNet-LVH accurately quantified ventricular parameters (R2 of 0.96 and 0.90 respectively) and detected cardiac amyloidosis (AUC 0.79) and hypertrophic cardiomyopathy (AUC 0.89) on the domestic external validation site. Leveraging measurements across multiple heart beats, our model can more accurately identify subtle changes in LV geometry and its causal etiologies. Compared to human experts, EchoNet-LVH is fully automated, allowing for reproducible, precise measurements, and lays the foundation for precision diagnosis of cardiac hypertrophy. As a resource to promote further innovation, we also make publicly available a large dataset of 23,212 annotated echocardiogram videos

INSPECT: A Multimodal Dataset for Pulmonary Embolism Diagnosis and Prognosis

Synthesizing information from multiple data sources plays a crucial role in the practice of modern medicine. Current applications of artificial intelligence in medicine often focus on single-modality data due to a lack of publicly available, multimodal medical datasets. To address this limitation, we introduce INSPECT, which contains de-identified longitudinal records from a large cohort of patients at risk for pulmonary embolism (PE), along with ground truth labels for multiple outcomes. INSPECT contains data from 19,402 patients, including CT images, radiology report impression sections, and structured electronic health record (EHR) data (i.e. demographics, diagnoses, procedures, vitals, and medications). Using INSPECT, we develop and release a benchmark for evaluating several baseline modeling approaches on a variety of important PE related tasks. We evaluate image-only, EHR-only, and multimodal fusion models. Trained models and the de-identified dataset are made available for non-commercial use under a data use agreement. To the best of our knowledge, INSPECT is the largest multimodal dataset integrating 3D medical imaging and EHR for reproducible methods evaluation and research

A decade in review after Idiopathic Scoliosis was first called a complex trait-A tribute to the late Dr. Yves Cotrel for his support in studies of etiology of scoliosis

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development

A decade in review after Idiopathic Scoliosis was first called a complex trait-A tribute to the late Dr. Yves Cotrel for his support in studies of etiology of scoliosis

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development

A Chemical Glycoproteomics Platform Reveals O-GlcNAcylation of Mitochondrial Voltage-Dependent Anion Channel 2

SummaryProtein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is a critical cell signaling modality, but identifying signal-specific O-GlcNAcylation events remains a significant experimental challenge. Here, we describe a method for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated proteins and use it to identify the mitochondrial voltage-dependent anion channel 2 (VDAC2) as an O-GlcNAc substrate. VDAC2−/− cells resist the mitochondrial dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating a functional connection between O-GlcNAc signaling and mitochondrial physiology through VDAC2. More broadly, our method will enable the discovery of signal-specific O-GlcNAcylation events in a wide array of experimental contexts

Unusual Electrical Conductivity Driven by Localized Stoichiometry Modification at Vertical Epitaxial Interfaces

Precise control of lattice mismatch accommodation and cation interdiffusion across the interface is critical to modulate correlated functionalities in epitaxial heterostructures, particularly when the interface composition is positioned near a compositional phase transition boundary. Here we select La1-xSrxMnO3 (LSMO) as a prototypical phase transition material and establish vertical epitaxial interfaces with NiO to explore the strong interplay between strain accommodation, stoichiometry modification, and localized electron transport across the interface. It is found that localized stoichiometry modification overcomes the plaguing dead layer problem in LSMO and leads to strongly directional conductivity, as manifested by more than three orders of magnitude difference between out-of-plane to in-plane conductivity. Comprehensive structural characterization and transport measurements reveal that this emerging behavior is related to a compositional change produced by directional cation diffusion that pushes the LSMO phase transition from insulating into metallic within an ultrathin interface region. This study explores the nature of unusual electric conductivity at vertical epitaxial interfaces and establishes an effective route for engineering nanoscale electron transport for oxide electronics