Manipulation of visual biofeedback during gait with a time delayed adaptive Virtual Mirror Box.

A mirror placed in the mid-sagittal plane of the body has been used to reduce phantom limb pain and improve movement function in medical conditions characterised by asymmetrical movement control. The mirrored illusion of unimpaired limb movement during gait might enhance the effect, but a physical mirror is only capable of showing parallel movement of limbs in real time typically while sitting. We aimed to overcome the limitations of physical mirrors by developing and evaluating a Virtual Mirror Box which delays the mirrored image of limbs during gait to ensure temporal congruency with the impaired physical limb

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

A shared data approach more accurately represents the rates and patterns of violence with injury assaults

Background To investigate whether sharing and linking routinely collected violence data across health and criminal justice systems can provide a more comprehensive understanding of violence, establish patterns of under-reporting and better inform the development, implementation and evaluation of violence prevention initiatives. Methods Police violence with injury (VWI) crimed data and emergency department (ED) assault attendee data for South Wales were collected between 1 April 2014 and 31 March 2016 to examine the rates and patterns of VWI. Person identifiable data (PID) were cross-referenced to establish if certain victims or events were less likely to be reported to criminal justice services. Results A total of 18 316 police crimed VWI victims and 10 260 individual ED attendances with an assault-related injury were considered. The majority of ED assault attendances (59.0%) were unknown to police. The key demographic identified as under-reporting to police were young males aged 18-34 years, while a significant amount of non-reported assaults involved a stranger. The combined monthly age-standardised rates were recalculated and on average were 74.7 (95% CI 72.1 to 77.2) and 66.1 (95% CI 64.0 to 68.2) per 100 000 population for males and females, respectively. Consideration of the additional ED cases resulted in a 35.3% and 18.1% increase on the original police totals for male and female VWI victims. Conclusions This study identified that violence is currently undermeasured, demonstrated the importance of continued sharing of routinely collected ED data and highlighted the benefits of using PID from a number of services in a linked way to provide a more comprehensive picture of violence

Cirsium species show disparity in patterns of genetic variation at their range-edge, despite similar patterns of reproduction and isolation

Genetic variation was assessed across the UK geographical range of Cirsium acaule and Cirsium heterophyllum. A decline in genetic diversity and increase in population divergence approaching the range edge of these species was predicted based on parallel declines in population density and seed production reported seperately. Patterns were compared with UK populations of the widespread Cirsium arvense.Populations were sampled along a latitudinal transect in the UK and genetic variation assessed using microsatellite markers. Cirsium acaule shows strong isolation by distance, a significant decline in diversity and an increase in divergence among range-edge populations. Geographical structure is also evident in C. arvense, whereas no such patterns are seen in C.heterophyllum. There is a major disparity between patterns of genetic variation in C. acaule and C. heterophyllum despite very similar patterns in seed production and population isolation in these species. This suggests it may be misleading to make assumptions about the geographical structure of genetic variation within species based solely on the present-day reproduction and distribution of populations

Associations between ACTN3 and OPPERA pain-related genes in malocclusion

We have investigated an orthognathic surgery population to determine how variation in masticatory muscle gene expression and genotype plays a key role in development of both jaw-deformation malocclusion and temporomandibular joint disorders (TMD). A gene of particular interest is ACTN3 since the common R577X polymorphism results in α-actinin-3 protein loss, reduced myofiber Z-disc structural integrity in skeletal muscle and decreased osteoblast/osteoclast activity in bone formation. Secondly, since the prevalence of TMD in this population is quite high (30%) we sought to determine if genes related to pain processes─previously identified in the Orofacial Pain: Prospective Evaluation and Risk Assessment Study (OPPERA) were differentially expressed

A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 ± 0.14 × 10(6)/ml), in comparison with subjects carrying only one copy of those alleles (0.46 ± 0.19 × 10(6)/ml) and subjects without any copy of those alleles (0.79 ± 0.15 × 10(6)/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 ± 0.14; 0.45 ± 0.21 and 0.41 ± 0.17 × 10(6)/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed

Genomics of Divergence along a Continuum of Parapatric Population Differentiation

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1)

Multivariate Approximations to Portfolio Return Distribution

This article proposes a three-step procedure to estimate portfolio return distributions under the multivariate Gram-Charlier (MGC) distribution. The method combines quasi maximum likelihood (QML) estimation for conditional means and variances and the method of moments (MM) estimation for the rest of the density parameters, including the correlation coefficients. The procedure involves consistent estimates even under density misspecification and solves the so-called ‘curse of dimensionality’ of multivariate modelling. Furthermore, the use of a MGC distribution represents a flexible and general approximation to the true distribution of portfolio returns and accounts for all its empirical regularities. An application of such procedure is performed for a portfolio composed of three European indices as an illustration. The MM estimation of the MGC (MGC-MM) is compared with the traditional maximum likelihood of both the MGC and multivariate Student’s t (benchmark) densities. A simulation on Value-at-Risk (VaR) performance for an equally weighted portfolio at 1% and 5% confidence indicates that the MGC-MM method provides reasonable approximations to the true empirical VaR. Therefore, the procedure seems to be a useful tool for risk managers and practitioners