Robotics Platforms Incorporating Manipulators Having Common Joint Designs

Manipulators in accordance with various embodiments of the invention can be utilized to implement statically stable robots capable of both dexterous manipulation and versatile mobility. Manipulators in accordance with one embodiment of the invention include: an azimuth actuator; three elbow joints that each include two actuators that are offset to allow greater than 360 degree rotation of each joint; a first connecting structure that connects the azimuth actuator and a first of the three elbow joints; a second connecting structure that connects the first elbow joint and a second of the three elbow joints; a third connecting structure that connects the second elbow joint to a third of the three elbow joints; and an end-effector interface connected to the third of the three elbow joints

Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10−10) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10−4, 1.8×10−4, and 2.2×10−4 respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Family studies of type 1 diabetes reveal additive and epistatic effects between MGAT1 and three other polymorphisms

In a recent study of Multiple Sclerosis (MS), we observed additive effects and epistatic interactions between variants of four genes that converge to induce T cell hyper-activity by altering Asn-(N) linked protein glycosylation: namely, the Golgi enzyme MGAT1, cytotoxic T-lymphocyte antigen 4 (CTLA-4), interleukin-2 receptor-α (IL2RA) and interleukin-7 receptor-α (IL7RA). As the CTLA-4, IL2RA and IL7RA variants are associated with Type 1 Diabetes (T1D), we examined for joint effects in T1D. Employing a novel conditional logistic regression for family-based datasets, epistatic and additive effects were observed using 1,423 multiplex families from the Type 1 Diabetes Genetic Consortium dataset. The IL2RA and IL7RA variants had univariate association in MS and T1D, while the MGAT1 and CTLA-4 variants associated with only MS or T1D, respectively. However, similar to MS, the MGAT1 variant haplotype interacted with CTLA4 (p=0.03), and a combination of IL2RA and IL7RA (p=0.01). The joint effects of MGAT1, CTLA4, IL2RA, IL7RA and the two interactions using a multiple conditional logistic regression were statistically highly significant (p<5×10(−10)). The MGAT1 - CTLA-4 interaction was replicated (p=0.01) in 179 trio families from the Genetics of Kidneys in Diabetes study. These data are consistent with defective N-glycosylation of T cells contributing to T1D pathogenesis

Nail biology and nail science.

The nail plate is the permanent product of the nail matrix. Its normal appearance and growth depend on the integrity of several components: the surrounding tissues or perionychium and the bony phalanx that are contributing to the nail apparatus or nail unit. The nail is inserted proximally in an invagination practically parallel to the upper surface of the skin and laterally in the lateral nail grooves. This pocket-like invagination has a roof, the proximal nail fold and a floor, the matrix from which the nail is derived. The germinal matrix forms the bulk of the nail plate. The proximal element forms the superficial third of the nail whereas the distal element provides its inferior two-thirds. The ventral surface of the proximal nail fold adheres closely to the nail for a short distance and forms a gradually desquamating tissue, the cuticle, made of the stratum corneum of both the dorsal and the ventral side of the proximal nail fold. The cuticle seals and therefore protects the ungual cul-de-sac. The nail plate is bordered by the proximal nail fold which is continuous with the similarly structured lateral nail fold on each side. The nail bed extends from the lunula to the hyponychium. It presents with parallel longitudinal rete ridges. This area, by contrast to the matrix has a firm attachment to the nail plate and nail avulsion produces a denudation of the nail bed. Colourless, but translucent, the highly vascular connective tissue containing glomus organs transmits a pink colour through the nail. Among its multiple functions, the nail provides counterpressure to the pulp that is essential to the tactile sensation involving the fingers and to the prevention of the hypertrophy of the distal wall tissue, produced after nail loss of the great toe nail.Journal ArticleFLWINinfo:eu-repo/semantics/publishe