Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks in the lab/clinic, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users’ performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb

Electrical, morphological and structural properties of RF magnetron sputtered Mo thin films for application in thin film photovoltaic solar cells

Molybdenum (Mo) thin films were deposited using radio frequency magnetron sputtering, for application as a metal back contact material in ‘‘substrate configuration’’ thin film solar cells. The variations of the electrical, morphological, and structural properties of the deposited films with sputtering pressure, sputtering power and post-deposition annealing were determined. The electrical conductivity of the Mo films was found to increase with decreasing sputtering pressure and increasing sputtering power. X-ray diffraction data showed that all the films had a (110) preferred orientation that became less pronounced at higher sputtering power while being relatively insensitive to process pressure. The lattice stress within the films changed from tensile to compressive with increasing sputtering power and the tensile stress increased with increasing sputtering pressure. The surface morphology of the films changed from pyramids to cigar-shaped grains for a sputtering power between 100 and 200 W, remaining largely unchanged at higher power. These grains were also observed to decrease in size with increasing sputtering pressure. Annealing the films was found to affect the resistivity and stress of the films. The resistivity increased due to the presence of residual oxygen and the stress changed from tensile to compressive. The annealing step was not found to affect the crystallisation and grain growth of the Mo films

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

BACKGROUND: After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. METHODS: Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. RESULTS: ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. CONCLUSION: In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

BACKGROUND: A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. PRESENTATION OF THE HYPOTHESIS: Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. TESTING THE HYPOTHESIS: Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments

LGR6 Is a High Affinity Receptor of R-Spondins and Potentially Functions as a Tumor Suppressor

BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LGR4 and LGR5. LGR6 was found as one of the novel genes mutated in colon cancer through total exon sequencing and its promoter region is hypermethylated in 20-50% of colon cancer cases. In the skin, LGR6 marks a population of stem cells that can give rise to all cell lineages. Recently, we and others demonstrated that LGR4 and LGR5 function as receptors of R-spondins to potentiate Wnt/β-catenin signaling. However, the binding affinity and functional response of LGR6 to R-spondins, and the activity of colon cancer mutants of LGR6 have not been determined. PRINCIPAL FINDINGS: We found that LGR6 also binds and responds to R-spondins 1-3 with high affinity to enhance Wnt/β-catenin signaling through increased LRP6 phosphorylation. Similar to LGR4 and LGR5, LGR6 is not coupled to heterotrimeric G proteins or to β-arrestin following R-spondin stimulation. Functional and expression analysis of three somatic mutations identified in colon cancer samples indicates that one mutant fails to bind and respond to R-spondin (loss-of-function), but the other two have no significant effect on receptor function. Overexpression of wild-type LGR6 in HeLa cells leads to increased cell migration following co-treatment with R-spondin1 and Wnt3a when compared to vector control cells or cells overexpressing the loss-of-function mutant. CONCLUSIONS: LGR6 is a high affinity receptor for R-spondins 1-3 and potentially functions as a tumor suppressor despite its positive effect on Wnt/β-catenin signaling

Tracking Antigen-Specific T-Cells during Clinical Tolerance Induction in Humans

Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3–5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets

Being Ready to Treat Ebola Virus Disease Patients

An unprecedented number of health care professionals from a variety of clinical settings, in a wide range of countries are thinking about, preparing for and caring for Ebola virus disease (EVD) patients. Guidance documents on infection prevention and control (IPC) practice and clinical care have been produced by organizations with EVD experience.1–3 The World Health Organization (WHO) produces guidance for implementation across a wide range of resource settings. Medecin Sans Frontières produces guidance for medical team activities across the outbreak. The Centers for Disease Control and Prevention (CDC) focus on measures which can be taken by the United States health system and extrapolated by others involved in preparedness and response. There are no short cuts to clinical preparedness for EVD. These documents and their revisions should be reviewed carefully. As important as guidance documents are, many lessons must be learned from specific hands-on experience. The WHO has mobilized clinical consultants in support of EVD response in each of the affected countries in West Africa. This short list of key points attempts to consolidate practical lessons learned that do not always percolate into technical documents. Having landed in unconstrained, resource-limited settings at the start of local EVD clinical operations in an outbreak, and more established EVD care centers, we hope that others might adopt some of these lessons and avoid some of the risks inherent to the steep learning curve associated with delivering EVD care. The points are geared toward the daily care of patients as opposed to the critical mechanics of establishing a care center and developing its procedures. They are focused on the outbreak setting and also have relevance to the referral hospital setting

A Synthesis of Tagging Studies Examining the Behaviour and Survival of Anadromous Salmonids in Marine Environments

This paper synthesizes tagging studies to highlight the current state of knowledge concerning the behaviour and survival of anadromous salmonids in the marine environment. Scientific literature was reviewed to quantify the number and type of studies that have investigated behaviour and survival of anadromous forms of Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), brown trout (Salmo trutta), steelhead (Oncorhynchus mykiss), and cutthroat trout (Oncorhynchus clarkii). We examined three categories of tags including electronic (e.g. acoustic, radio, archival), passive (e.g. external marks, Carlin, coded wire, passive integrated transponder [PIT]), and biological (e.g. otolith, genetic, scale, parasites). Based on 207 papers, survival rates and behaviour in marine environments were found to be extremely variable spatially and temporally, with some of the most influential factors being temperature, population, physiological state, and fish size. Salmonids at all life stages were consistently found to swim at an average speed of approximately one body length per second, which likely corresponds with the speed at which transport costs are minimal. We found that there is relatively little research conducted on open-ocean migrating salmonids, and some species (e.g. masu [O. masou] and amago [O. rhodurus]) are underrepresented in the literature. The most common forms of tagging used across life stages were various forms of external tags, coded wire tags, and acoustic tags, however, the majority of studies did not measure tagging/handling effects on the fish, tag loss/failure, or tag detection probabilities when estimating survival. Through the interdisciplinary application of existing and novel technologies, future research examining the behaviour and survival of anadromous salmonids could incorporate important drivers such as oceanography, tagging/handling effects, predation, and physiology

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /