Development of a Protocol to Test Proprioceptive Utilization as a Predictor for Sensorimotor Adaptability

Astronauts returning from space flight show significant inter-subject variations in their abilities to readapt to a gravitational environment because of their innate sensory weighting. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. We hypothesize participant's ability to utilize individual sensory information (vision, proprioception and vestibular) influences adaptation in sensorimotor performance after space flight. The goal of this study is to develop a reliable protocol to test proprioceptive utilization in a functional postural control task. Subjects "stand" in a supine position while strapped to a backpack frame holding a friction-free device using air-bearings that allow the subject to move freely in the frontal plane, similar to when in upright standing. The frame is attached to a pneumatic cylinder, which can provide different levels of a gravity-like force that the subject must balance against to remain "upright". The supine posture with eyes closed ensures reduced vestibular and visual contribution to postural control suggesting somatosensory and/or non-otolith vestibular inputs will provide relevant information for maintaining balance control in this task. This setup is called the gravity bed. Fourteen healthy subjects carried out three trials each with eyes open alternated with eyes closed, "standing" on their dominant leg in the gravity bed environment while loaded with 60 percent of their body weight. Subjects were instructed to: "use your sense of sway about the ankle and pressure changes under the foot to maintain balance." Maximum length of a trial was 45 seconds. A force plate underneath the foot recorded forces and moments during the trial and an inertial measurement unit (IMU) attached on the backpack's frame near the center of mass of the subject recorded upper body postural responses. Series of linear and non-linear analyses were carried out on several force plate and IMU data including stabilogram diffusion analysis on the center of pressure (COP) to find a subset of parameters that were sensitive to detect differences in postural performance between eyes open and closed conditions. Results revealed that seven parameters (root mean square (RMS) of medio-lateral (ML) COP, range of ML COP, RMS of roll moment, range of trunk roll, minimum time-to-boundary (TTB), integrated TTB, and critical mean square planar displacement (delta r (sup 2) (sub c)) were significantly different between eyes open and closed conditions. We will present data to show the efficacy of using performance in single leg stance with eyes closed on the gravity bed to assess individuals' ability to utilize proprioceptive information in a functional postural control task to predict re-adaptation for sensorimotor and functional performance

Sensorimotor Predictors of Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can potentially be used to predict early performance following G-transitions such as return to Earth on a set of sensorimotor tasks. Astronauts are being recruited who previously participated in sensorimotor field tests and/or dynamic posturography (MedB) within R+1 days following long-duration spaceflight

Sequence variant at 4q25 near PITX2 associates with appendicitis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesAppendicitis is one of the most common conditions requiring acute surgery and can pose a threat to the lives of affected individuals. We performed a genome-wide association study of appendicitis in 7,276 Icelandic and 1,139 Dutch cases and large groups of controls. In a combined analysis of the Icelandic and Dutch data, we detected a single signal represented by an intergenic variant rs2129979 [G] close to the gene PITX2 associating with increased risk of appendicitis (OR = 1.15, P = 1.8 × 10(-11)). We only observe the association in patients diagnosed in adulthood. The marker is close to, but distinct from, a set of markers reported to associate with atrial fibrillation, which have been linked to PITX2. PITX2 has been implicated in determination of right-left symmetry during development. Anomalies in organ arrangement have been linked to increased prevalence of gastrointestinal and intra-abdominal complications, which may explain the effect of rs2129979 on appendicitis risk

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption.We usemultiparameter geophysical and geochemical data to show that the 110-squarekilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, nearexponential decline of both collapse rate and the intensity of the 180-day-long eruption

Rare and Common Variants Conferring Risk of Tooth Agenesis

We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach

Genetic insight into sick sinus syndrome

Aims. The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results. We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10⁻²⁰), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). Conclusion. We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes

Evaluation of a website providing information on regional health care services for patients with rheumatoid arthritis: an observational study

Studies on the effectiveness of information provision for patients with arthritis through the Internet are scarce. This study aimed to describe rheumatoid arthritis (RA) patients’ knowledge and information needs before and after launching a website providing information on regional health care services for patients with rheumatic conditions. The intervention consisted of a weekly updated website comprising practical information on regional health care services for patients with arthritis. In addition, patients were offered information leaflets and an information meeting. Before (T1) and 24 months after (T2) the website was launched, a random sample of 400 RA patients filled in a questionnaire regarding knowledge and information need (scores 0–18) about accessibility and contents of 18 regional health care services. Two hundred and fifty-one patients returned the questionnaire (response rate 63%) at T1 and 200 patients (50%) at T2, respectively, with 160 paired observations (112 females (70%), mean age 60.4 years (SD 9.9)). The total score for insufficient knowledge about contents decreased from 9.3 (SD 4.9) to 8.5 (SD 4.8; p = 0.03) and for accessibility from 8.6 (SD 4.7) to 8.4 (SD 4.9; p = 0.59). Total score for information need about contents decreased from 4.2 (SD 4.5) to 1.9 (SD 2.9; p < 0.01) and for accessibility from 3.6 (SD 4.5) to 1.4 (SD 2.4; p < 0.01) (paired t-tests)

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption.We usemultiparameter geophysical and geochemical data to show that the 110-squarekilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, nearexponential decline of both collapse rate and the intensity of the 180-day-long eruption.</p

Predictive Measures of Locomotor Performance on an Unstable Walking Surface

Locomotion requires integration of visual, vestibular, and somatosensory information to produce the appropriate motor output to control movement. The degree to which these sensory inputs are weighted and reorganized in discordant sensory environments varies by individual and may be predictive of the ability to adapt to novel environments. The goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to inform the design of training countermeasures designed to enhance the ability of astronauts to adapt to gravitational transitions improving balance and locomotor performance after a Mars landing and enhancing egress capability after a landing on Earth