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

Compound heterozygous mutations in UBA5 causing early-onset epileptic encephalopathy in two sisters.

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 FilesEpileptic encephalopathies are a group of childhood epilepsies that display high phenotypic and genetic heterogeneity. The recent, extensive use of next-generation sequencing has identified a large number of genes in epileptic encephalopathies, including UBA5 in which biallelic mutations were first described as pathogenic in 2016 (Colin E et al., Am J Hum Genet 99(3):695-703, 2016. Muona M et al., Am J Hum Genet 99(3):683-694, 2016). UBA5 encodes an activating enzyme for a post-translational modification mechanism known as ufmylation, and is the first gene from the ufmylation pathway that is linked to disease.We sequenced the genomes of two sisters with early-onset epileptic encephalopathy along with their unaffected parents in an attempt to find a genetic cause for their condition. The sisters, born in 2004 and 2006, presented with infantile spasms at six months of age, which later progressed to recurrent, treatment-resistant seizures. We detected a compound heterozygous genotype in UBA5 in the sisters, a genotype not seen elsewhere in an Icelandic reference set of 30,067 individuals nor in public databases. One of the mutations, c.684G > A, is a paternally inherited exonic splicing mutation, occuring at the last nucleotide of exon 7 of UBA5. The mutation is predicted to disrupt the splice site, resulting in loss-of-function of one allele of UBA5. The second mutation is a maternally inherited missense mutation, p.Ala371Thr, previously reported as pathogenic when in compound heterozygosity with a loss-of-function mutation in UBA5 and is believed to produce a hypomorphic allele. Supportive of this, we have identified three adult Icelanders homozygous for the p.Ala371Thr mutation who show no signs of neurological disease.We describe compound heterozygous mutations in the UBA5 gene in two sisters with early-onset epileptic encephalopathy. To our knowledge, this is the first description of mutations in UBA5 since the initial discovery that pathogenic biallelic variants in the gene cause early-onset epileptic encephalopathy. We further provide confirmatory evidence that p.Ala371Thr is a hypomorphic mutation, by presenting three adult homozygotes who show no signs of neurological disease

Social and ethical criteria for prioritizing patients: a survey of students and health professionals in Portugal

O estudo quali-quantitativo explora o dilema ético da microalocação dos recursos da saúde. Objetiva identificar e comparar a opinião de dois grupos da sociedade portuguesa - estudantes e profissionais de saúde sobre a importância das características pessoais dos pacientes no momento de os priorizar e se as escolhas se explicam por referenciais bioéticos de caráter utilitaristas ou deontológicos. Os dados foram recolhidos através de um questionário aplicado a uma amostra de 180 estudantes universitários e 60 profissionais de saúde. Os respondentes perante hipotéticos cená- rios de emergência clínica tiveram de escolher de entre dois pacientes (distinguidos por idade, sexo, responsabilidade social, situação económica e laboral, comportamentos lesivos da saúde e registo criminal) quem tratar e justificar a escolha. Foram usados testes estatísticos de associação para comparar as respostas dos dois grupos e análise de conteúdo para categorizar as justificações. Os resultados sugerem a existência de diferenças nas escolhas dos dois grupos, com os profissionais de saúde a revelarem aceitar menos a utilização de critérios sociais em contexto de escassez e coexistência de critérios utilitaristas e deontológicos, com predomínio da eficiência por parte dos profissionais de saúde e da equidade por parte dos estudantesThis qualitative/quantitative study examines the ethical dilemma of microallocation of health resources. It seeks to identify and compare the opinion of two groups in Portuguese society – students and health professionals – on the importance of personal characteristics of patients at the moment of prioritizing them and if the choices can be explained by bioethical references of a utilitarian or deontological nature. Data were collected by means of a questionnaire administered to a sample of 180 students and 60 health professionals. Faced with hypothetical emergency scenarios, the respondents had to choose between two patients (distinguished by: age, gender, social responsibility, economic and employment situation, harmful health behaviors and criminal record), duly selecting who to treat and then justifying their choice. The results suggest the existence of differences in choices between the two groups, with health professionals revealing they are less prepared to accept the use of social criteria in a context of scarce resources and co-existence of utilitarian and deontological criteria, with a predominance of efficiency on the part of health professionals and equity on the part of students.info:eu-repo/semantics/publishedVersio

Design and Mechanical Characterization of a Variable Stiffness ESR Foot Prosthesis

In this article, MyFlex- epsilon , an ESR foot prosthesis equipped with a light and manually adjustable mechanism that allows for varying its stiffness in the sagittal plane, and a systematic approach to calculate its rotation-stiffness curves are presented. Through a design of experiment conducted numerically using a two-dimensional (2D) finite element (FE) model, calibrated experimentally, a geometric parameter whose variation alters the sagittal plane stiffness of a prosthesis originally designed with invariable stiffness, MyFlex- delta , was determined. After building the mechanism and integrating it into MyFlex- delta to obtain MyFlex- epsilon , the displacement-force curves of the latter through tests equivalent to the static tests specified in ISO 10328 were determined. Based on the experimental results, the 2D FE model of MyFlex- epsilon was built and calibrated to determine its rotation-stiffness curves in the sagittal plane. Comparing the rotation-stiffness curves obtained with the most compliant setting to the stiffest setting, stiffness variations of 119%, 122%, 138%, and 162% at plantarflexion angles of -5 degrees and -2.5 degrees, and dorsiflexion angles of 7.5 degrees and 15 degrees, respectively, were found

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

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

Surface elevation change and mass balance of Icelandic ice caps derived from swath mode CryoSat-2 altimetry

We apply swath processing to CryoSat-2 interferometric mode data acquired over the Icelandic ice caps to generate maps of rates of surface elevation change at 0.5 km postings. This high-resolution mapping reveals complex surface elevation changes in the region, related to climate, ice dynamics, and subglacial geothermal and magmatic processes. We estimate rates of volume and mass change independently for the six major Icelandic ice caps, 90% of Iceland's permanent ice cover, for five glaciological years between October 2010 and September 2015. Annual mass balance is highly variable; during the 2014/2015 glaciological year, the Vatnajökull ice cap (~70% of the glaciated area) experienced positive mass balance for the first time since 1992/1993. Our results indicate that between glaciological years 2010/2011and 2014/2015 Icelandic ice caps have lost 5.8 ± 0.7 Gt a−1 on average, ~40% less than the preceding 15 years, contributing 0.016 ± 0.002 mm a−1 to sea level rise

Structural fea-based design and functionality verification methodology of energy-storing-and-releasing prosthetic feet

The prosthetic feet that are most often prescribed to individuals with K3/K4 levels of ambulation are the ESR feet. ESR stands for energy-storing and-releasing. The elastic energy is stored by the elastic elements in composite materials (carbon fiber or glass fiber). ESR feet must be developed and optimized in terms of stiffness, taking into account the loads that a healthy human foot undergoes and its kinematics while walking. So far, state-of-the-art analyses show that the literature approaches for prosthetic foot design are not based on a systematic methodology. With the aim of optimizing the stiffness of ESR feet following a methodological procedure, a methodology based on finite element structural analysis, standard static testing (ISO 10328) and functional verification was optimized and it is presented in this paper. During the path of optimization of the foot prototypes, this methodology was validated experimentally. It includes the following: (i) geometry optimization through two-dimensional finite element analysis; (ii) material properties optimization through three-dimensional finite element analysis; (iii) validation test on physical prototypes; (iv) functionality verification through dynamic finite element analysis. The design and functional verification of MyFlex-γ, a three-blade ESR foot prosthesis, is presented to describe the methodology and demonstrate its usability

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

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.