Surgical vs Conservative Treatments for Adolescent Shoulder Instability

Shoulder instability following an anterior shoulder dislocation is common in active adolescent populations and can have negative long-term impacts on activities of daily living and competitive physical activities. Historically, shoulder instability following anterior shoulder dislocation is treated surgically due to the high risk of recurrent instability. However, conservative treatments may be appropriate in certain adolescent populations due to skeletal immaturity. This article investigates the effectiveness of conservative therapy compared to surgical repair in the adolescent population with shoulder instability following anterior shoulder dislocation

Effects of time since fire on birds : how informative are generalized fire response curves for conservation management?

Fire is both a widespread natural disturbance that affects the distribution of species and a tool that can be used to manage habitats for species. Knowledge of temporal changes in the occurrence of species after fire is essential for conservation management in fire-prone environments. Two key issues are: whether postfire responses of species are idiosyncratic or if multiple species show a limited number of similar responses; and whether such responses to time since fire can predict the occurrence of species across broad spatial scales. We examined the response of bird species to time since fire in semiarid shrubland in southeastern Australia using data from surveys at 499 sites representing a 100-year chronosequence. We used nonlinear regression to model the probability of occurrence of 30 species with time since fire in two vegetation types, and compared species\u27 responses with generalized response shapes from the literature. The occurrence of 16 species was significantly influenced by time since fire: they displayed six main responses consistent with generalized response shapes. Of these 16 species, 15 occurred more frequently in mid- or later-successional vegetation (&gt;20 years since fire), and only one species occurred more often in early succession (&lt;5 years since fire). The models had reasonable predictive ability for eight species, some predictive ability for seven species, and were little better than random for one species. Bird species displayed a limited range of responses to time since fire; thus a small set of fire ages should allow the provision of habitat for most species. Postfire successional changes extend for decades and management of the age class distribution of vegetation will need to reflect this timescale. Response curves revealed important seral stages for species and highlighted the importance of mid- to late-successional vegetation (&gt;20 years). Although time since fire clearly influences the distribution of numerous bird species, predictive models of the spatial distribution of species in fire-prone landscapes need to incorporate other factors in addition to time since fire.<br /

Canonical Correlation Analysis and Partial Least Squares for identifying brain-behaviour associations: a tutorial and a comparative study

Canonical Correlation Analysis (CCA) and Partial Least Squares (PLS) are powerful multivariate methods for capturing associations across two modalities of data (e.g., brain and behaviour). However, when the sample size is similar or smaller than the number of variables in the data, CCA and PLS models may overfit, i.e., find spurious associations that generalise poorly to new data. Dimensionality reduction and regularized extensions of CCA and PLS have been proposed to address this problem, yet most studies using these approaches have some limitations. This work gives a theoretical and practical introduction into the most common CCA/PLS models and their regularized variants. We examine the limitations of standard CCA and PLS when the sample size is similar or smaller than the number of variables. We discuss how dimensionality reduction and regularization techniques address this problem and explain their main advantages and disadvantages. We highlight crucial aspects of the CCA/PLS analysis framework, including optimising the hyperparameters of the model and testing the identified associations for statistical significance. We apply the described CCA/PLS models to simulated data and real data from the Human Connectome Project and the Alzheimer's Disease Neuroimaging Initiative (both of n>500). We use both low and high dimensionality versions of each data (i.e., ratios between sample size and variables in the range of ∼1-10 and ∼0.1-0.01) to demonstrate the impact of data dimensionality on the models. Finally, we summarize the key lessons of the tutorial

Schistosoma mansoni Larvae Do Not Expand or Activate Foxp3+ Regulatory T Cells during Their Migratory Phase

Foxp3+ regulatory T (Treg) cells play a key role in suppression of immune responses during parasitic helminth infection, both by controlling damaging immunopathology and by inhibiting protective immunity. During the patent phase of Schistosoma mansoni infection, Foxp3+ Treg cells are activated and suppress egg-elicited Th2 responses, but little is known of their induction and role during the early prepatent larval stage of infection. We quantified Foxp3+ Treg cell responses during the first 3 weeks of murine S. mansoni infection in C57BL/6 mice, a time when larval parasites migrate from the skin and transit the lungs en route to the hepatic and mesenteric vasculature. In contrast to other helminth infections, S. mansoni did not elicit a Foxp3+ Treg cell response during this early phase of infection. We found that the numbers and proportions of Foxp3+ Treg cells remained unchanged in the lungs, draining lymph nodes, and spleens of infected mice. There was no increase in the activation status of Foxp3+ Treg cells upon infection as assessed by their expression of CD25, Foxp3, and Helios. Furthermore, infection failed to induce Foxp3+ Treg cells to produce the suppressive cytokine interleukin 10 (IL-10). Instead, only CD4+ Foxp3− IL-4+ Th2 cells showed increased IL-10 production upon infection. These data indicate that Foxp3+ Treg cells do not play a prominent role in regulating immunity to S. mansoni larvae and that the character of the initial immune response invoked by S. mansoni parasites contrasts with the responses to other parasitic helminth infections that promote rapid Foxp3+ Treg cell responses

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

Multiple Holdouts With Stability: Improving the Generalizability of Machine Learning Analyses of Brain-Behavior Relationships.

BACKGROUND:In 2009, the National Institute of Mental Health launched the Research Domain Criteria, an attempt to move beyond diagnostic categories and ground psychiatry within neurobiological constructs that combine different levels of measures (e.g., brain imaging and behavior). Statistical methods that can integrate such multimodal data, however, are often vulnerable to overfitting, poor generalization, and difficulties in interpreting the results. METHODS:We propose an innovative machine learning framework combining multiple holdouts and a stability criterion with regularized multivariate techniques, such as sparse partial least squares and kernel canonical correlation analysis, for identifying hidden dimensions of cross-modality relationships. To illustrate the approach, we investigated structural brain-behavior associations in an extensively phenotyped developmental sample of 345 participants (312 healthy and 33 with clinical depression). The brain data consisted of whole-brain voxel-based gray matter volumes, and the behavioral data included item-level self-report questionnaires and IQ and demographic measures. RESULTS:Both sparse partial least squares and kernel canonical correlation analysis captured two hidden dimensions of brain-behavior relationships: one related to age and drinking and the other one related to depression. The applied machine learning framework indicates that these results are stable and generalize well to new data. Indeed, the identified brain-behavior associations are in agreement with previous findings in the literature concerning age, alcohol use, and depression-related changes in brain volume. CONCLUSIONS:Multivariate techniques (such as sparse partial least squares and kernel canonical correlation analysis) embedded in our novel framework are promising tools to link behavior and/or symptoms to neurobiology and thus have great potential to contribute to a biologically grounded definition of psychiatric disorders

Prostate Cancer Susceptibility Loci Identified on Chromosome 12 in African Americans

Prostate cancer (PCa) is a complex disease that disproportionately affects African Americans and other individuals of African descent. A number of regions across the genome have been associated to PCa, most of them with moderate effects. A few studies have reported chromosomal changes on 12p and 12q that occur during the onset and development of PCa but to date no consistent association of the disease with chromosome 12 polymorphic variation has been identified. In order to unravel genetic risk factors that underlie PCa health disparities we investigated chromosome 12 using ancestry informative markers (AIMs), which allow us to distinguish genomic regions of European or West African origin, and tested them for association with PCa. Additional SNPs were genotyped in those areas where significant signals of association were detected. The strongest signal was discovered at the SNP rs12827748, located upstream of the PAWR gene, a tumor suppressor, which is amply expressed in the prostate. The most frequent allele in Europeans was the risk allele among African Americans. We also examined vitamin D related genes, VDR and CYP27B1, and found a significant association of PCa with the TaqI polymorphism (rs731236) in the former. Although our results warrant further investigation we have uncovered a genetic susceptibility factor for PCa in a likely candidate by means of an approach that takes advantage of the differential contribution of parental groups to an admixed population

Regulatory T Cells in Human Lymphatic Filariasis: Stronger Functional Activity in Microfilaremics

Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria-specific immune responses during human filariasis. Microfilaremic (MF), chronic pathology (CP) and uninfected endemic normal (EN) individuals were selected in an area endemic for Brugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25hi cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg-depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responses were lower compared to EN and CP groups. Depletion of Tregs restored T cell as well as B cell proliferation in MF-positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressing proliferation and possibly Th2 cytokine responses to BmA. These suppressive effects were only observed in the MF group and not in EN or CP. These findings may be important when considering strategies for filarial treatment and the targeted prevention of filaria-induced lymphedema

Measurement of triple gauge boson couplings from WW production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb^-1. After combining with our previous measurements at centre-of-mass energies of 161-183 GeV we obtain k_g=0.97 +0.20 -0.16, g_1^z=0.991 +0.060 -0.057 and lambda_g=-0.110 +0.058 -0.055, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their SM values. These results are consistent with the Standard Model expectations.Comment: 28 pages, 8 figures, submitted to Eur. Phys. J.