Tenodesis Grasp Emulator: Kinematic Assessment of Wrist-Driven Orthotic Control

Wrist-driven orthotics have been designed to assist people with C6-7 spinal cord injury, however, the kinematic constraint imposed by such a control strategy can impede mobility and lead to abnormal body motion. This study characterizes body compensation using the novel Tenodesis Grasp Emulator, an adaptor orthotic that allows for the investigation of tenodesis grasping in subjects with unimpaired hand function. Subjects perform a series of grasp-and-release tasks in order to compare normal (test control) and constrained wrist-driven modes, showing significant compensation as a result of the constraint. A motor-augmented mode is also compared against traditional wrist-driven operation, to explore the potential role of hybrid human-robot control. We find that both the passive wrist-driven and motor-augmented modes fulfill different roles throughout various tasks tested. Thus, we conclude that a flexible control scheme that can alter intervention based on the task at hand holds the potential to reduce compensation in future work.Comment: 7 pages, 11 figures, submitted to International Conference on Robotics and Automation (ICRA) 2022. Video Supplement: https://youtu.be/NIgKg5R3Ro

Stellar Metallicities from SkyMapper Photometry II: Precise photometric metallicities of ∼\sim280,000 giant stars with [Fe/H] <−0.75< -0.75 in the Milky Way

The Milky Way's metal-poor stars are nearby ancient objects that are used to study early chemical evolution and the assembly and structure of the Milky Way. Here we present reliable metallicities of $\sim280,000$ stars with $-3.75 \lesssim$ [Fe/H] $\lesssim -0.75$ down to $g=17$ derived using metallicity-sensitive photometry from the second data release (DR2) of the SkyMapper Southern Survey. We use the dependency of the flux through the SkyMapper $v$ filter on the strength of the Ca II K absorption features, in tandem with SkyMapper $u,g,i$ photometry, to derive photometric metallicities for these stars. We find that metallicities derived in this way compare well to metallicities derived in large-scale spectroscopic surveys, and use such comparisons to calibrate and quantify systematics as a function of location, reddening, and color. We find good agreement with metallicities from the APOGEE, LAMOST, and GALAH surveys, based on a standard deviation of $\sigma\sim0.25$dex of the residuals of our photometric metallicities with respect to metallicities from those surveys. We also compare our derived photometric metallicities to metallicities presented in a number of high-resolution spectroscopic studies to validate the low metallicity end ([Fe/H] $< -2.5$) of our photometric metallicity determinations. In such comparisons, we find the metallicities of stars with photometric [Fe/H] $< -2.5$ in our catalog show no significant offset and a scatter of $\sigma\sim$0.31dex level relative to those in high-resolution work when considering the cooler stars ($g-i > 0.65$) in our sample. We also present an expanded catalog containing photometric metallicities of $\sim720,000$ stars as a data table for further exploration of the metal-poor Milky Way.Comment: 15 pages, 9 figures, 2 tables; submitted to ApJS and revised after one round of referee feedback. Full version of Table 2 in sourc

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Prevalence and Characteristics of Self-Reported Hypothyroidism and Its Association with Nonorgan-Specific Manifestations in US Sarcoidosis Patients: A Nationwide Registry Study

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01–1.6), antidepressant use (aOR 1.3, 95% CI 1.1–1.7), obesity (aOR 1.7, 95% CI 1.4–2.1), sleep apnoea (aOR 1.7, 95% CI 1.3–2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2–2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1–1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression

SPLUS J142445.34-254247.1: An R-Process Enhanced, Actinide-Boost, Extremely Metal-Poor star observed with GHOST

We report on the chemo-dynamical analysis of SPLUS J142445.34-254247.1, an extremely metal-poor halo star enhanced in elements formed by the rapid neutron-capture process. This star was first selected as a metal-poor candidate from its narrow-band S-PLUS photometry and followed up spectroscopically in medium-resolution with Gemini South/GMOS, which confirmed its low-metallicity status. High-resolution spectroscopy was gathered with GHOST at Gemini South, allowing for the determination of chemical abundances for 36 elements, from carbon to thorium. At [Fe/H]=-3.39, SPLUS J1424-2542 is one of the lowest metallicity stars with measured Th and has the highest logeps(Th/Eu) observed to date, making it part of the "actinide-boost" category of r-process enhanced stars. The analysis presented here suggests that the gas cloud from which SPLUS J1424-2542 was formed must have been enriched by at least two progenitor populations. The light-element (Z<=30) abundance pattern is consistent with the yields from a supernova explosion of metal-free stars with 11.3-13.4 Msun, and the heavy-element (Z>=38) abundance pattern can be reproduced by the yields from a neutron star merger (1.66Msun and 1.27Msun) event. A kinematical analysis also reveals that SPLUS J1424-2542 is a low-mass, old halo star with a likely in-situ origin, not associated with any known early merger events in the Milky Way.Comment: 26 pages, 11 figures, accepted for publication on Ap

Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation