In-vivo Measurement of Wrist Movements During the Dart-Throwing Motion Using Inertial Measurement Units

Background: This study investigates the dart-throwing motion (DTM) by comparing an inertial measurement unit-based system previously validated for basic motion tasks with an optoelectronic motion capture system. The DTM is interesting as wrist movement during many activities of daily living occur in this movement plane, but the complex movement is difficult to assess clinically. Methods: Ten healthy subjects were recorded while performing the DTM with their right wrist using inertial sensors and skin markers. Maximum range of motion obtained by the different systems and the mean absolute difference were calculated. Results: In the flexion-extension plane, both systems calculated a range of motion of 100◦ with mean absolute differences of 8◦ , while in the radial-ulnar deviation plane, a mean absolute difference of 17◦ and range of motion values of 48◦ for the optoelectronic system and 59◦ for the inertial measurement units were found. Conclusions: This study shows the challenge of comparing results of different kinematic motion capture systems for complex movements while also highlighting inertial measurement units as promising for future clinical application in dynamic and coupled wrist movements. Possible sources of error and solutions are discusse

Comparison of a New Inertial Sensor Based System with an Optoelectronic Motion Capture System for Motion Analysis of Healthy Human Wrist Joints

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p-values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings

Comparison of a New Inertial Sensor Based System with an Optoelectronic Motion Capture System for Motion Analysis of Healthy Human Wrist Joints

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p-values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings

Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model

Background High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways. Objective We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate. Methods INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS). Results INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033). Conclusion Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development

Extending PLE models into the mid-IR, far-IR & sub-mm

Simple pure luminosity evolution (PLE) models, in which galaxies brighten at high redshift due to increased star-formation rates (SFRs), are known to provide a good fit to the colours and number counts of galaxies throughout the optical and near-infrared. We show that optically defined PLE models, where dust reradiates absorbed optical light into infrared spectra composed of local galaxy templates, fit galaxy counts and colours out to 8um and to at least z=2.5. At 24-70um, the model is able to reproduce the observed source counts with reasonable success if 16% of spiral galaxies show an excess in mid-IR flux due to a warmer dust component and a higher SFR, in line with observations of local starburst galaxies. There remains an under-prediction of the number of faint-flux, high-z sources at 24um, so we explore how the evolution may be altered to correct this. At 160um and longer wavelengths, the model fails, with our model of normal galaxies accounting for only a few percent of sources in these bands. However, we show that a PLE model of obscured AGN, which we have previously shown to give a good fit to observations at 850um, also provides a reasonable fit to the Herschel/BLAST number counts and redshift distributions at 250-500um. In the context of a LCDM cosmology, an AGN contribution at 250-870um would remove the need to invoke a top-heavy IMF for high-redshift starburst galaxies, although the excellent fit of the galaxy PLE model at shorter wavelengths would still need to be explained.Comment: 14 pages, 11 figures; submitted to MNRA

The DEEP3 Galaxy Redshift Survey: Keck/DEIMOS Spectroscopy in the GOODS-N Field

We present the results of spectroscopic observations in the GOODS-N field completed using DEIMOS on the Keck II telescope as part of the DEEP3 Galaxy Redshift Survey. Observations of 370 unique targets down to a limiting magnitude of R = 24.4 yielded 156 secure redshifts. In addition to redshift information, we provide sky-subtracted one- and two-dimensional spectra of each target. Observations were conducted following the procedures of the Team Keck Redshift Survey (TKRS), thereby producing spectra that augment the TKRS sample while maintaining the uniformity of its spectral database.Comment: Accepted for publication in ApJS; 5 Pages, 2 Figures; Redshift Catalog and Spectra available at http://deep.berkeley.edu/GOODSN

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis

This document is the Accepted Manuscript version of the following article: Riessland et al., 'Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis', The American Journal of Human Genetics, Vol. 100 (2): 297-315, first published online 26 January 2017. The final, published version is available online at doi: http://dx.doi.org/10.1016/j.ajhg.2017.01.005 © 2017 American Society of Human Genetics.Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca(2+)-dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies.Peer reviewedFinal Accepted Versio

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

<p>Abstract</p> <p>Background</p> <p>Neramexane is a new substance that exhibits antagonistic properties at α₉α₁₀cholinergic nicotinic receptors and <it>N</it>-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus.</p> <p>Methods</p> <p>A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12).</p> <p>Results</p> <p>Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (<it>p </it>= 0.098 for 50 mg/d; <it>p </it>= 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with <it>p </it>values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence.</p> <p>Conclusions</p> <p>This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00405886</p

Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

Genetic deletion of murine Esco2 (an acetylase known to establish cohesin during S-phase and genetically linked to Roberts syndrome) results in embryonic lethality that can be molecularly linked to novel and specific functions of Esco2 at pericentric heterochromatin

Diversity Promotes Temporal Stability across Levels of Ecosystem Organization in Experimental Grasslands

The diversity–stability hypothesis states that current losses of biodiversity can impair the ability of an ecosystem to dampen the effect of environmental perturbations on its functioning. Using data from a long-term and comprehensive biodiversity experiment, we quantified the temporal stability of 42 variables characterizing twelve ecological functions in managed grassland plots varying in plant species richness. We demonstrate that diversity increases stability i) across trophic levels (producer, consumer), ii) at both the system (community, ecosystem) and the component levels (population, functional group, phylogenetic clade), and iii) primarily for aboveground rather than belowground processes. Temporal synchronization across studied variables was mostly unaffected with increasing species richness. This study provides the strongest empirical support so far that diversity promotes stability across different ecological functions and levels of ecosystem organization in grasslands