Modeling arsenic in European topsoils with a coupled semiparametric (GAMLSS-RF) model for censored data.

Arsenic (As) is a versatile heavy metalloid trace element extensively used in industrial applications. As is carcinogen, poses health risks through both inhalation and ingestion, and is associated with an increased risk of liver, kidney, lung, and bladder tumors. In the agricultural context, the repeated application of arsenical products leads to elevated soil concentrations, which are also affected by environmental and management variables.

Delayed Blunt Traumatic Carotid Artery Dissection After a Scooter Accident: A Case Report.

Introduction: Traumatic carotid artery dissections (CAD) are rare but produce potentially devastating injuries. Most patients develop symptoms within 72 hours of traumatic injury.

Case Report: We report the case of a 33-year-old, previously healthy male who presented to the emergency department for evaluation of transient, right-sided facial droop with visual changes.

Age-Related Electrocardiographic Characteristics of Male Junior Soccer Athletes.

Introduction: Very limited data exist on normal age-related ECG variations in adolescents and no data have been published regarding the ECG anomalies induced by intensive training, which are relevant in pre-participation screening for sudden cardiac death prevention in the adolescent athletic population. The purpose of this study was to establish normal age-related electrocardiographic measurements (P wave duration, PR interval, QRS duration, QT, and QTc interval) grouped according to 2-year age intervals.

Methods: A total of 2,151 consecutive healthy adolescent Soccer athletes (trained for a mean of 7.

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center.

Follicular T helper (T) cells orchestrate the germinal center (GC) response locally. T localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here.

Centile estimation for a proportion response variable.

This paper introduces two general models for computing centiles when the response variable Y can take values between 0 and 1, inclusive of 0 or 1. The models developed are more flexible alternatives to the beta inflated distribution. The first proposed model employs a flexible four parameter logit skew Student t (logitSST) distribution to model the response variable Y on the unit interval (0, 1), excluding 0 and 1.

Developing regional weight-for-age growth references for malaria-endemic countries to optimize age-based dosing of antimalarials.

Objective: To derive regional weight-for-age growth references to help optimize age-based dosing of antimalarials in Africa, the Americas, South-East Asia and the Western Pacific.

Methods: A weight-for-age database was constructed from pre-existing population-based anthropometric data obtained from household surveys and research groups. It contained data collected between 1995 and 2012 on 1,263,119 individuals (909,368 female, 353,751 male) older than 14 days and younger than 50 years in 64 malaria-endemic countries.

Automatic smoothing parameter selection in GAMLSS with an application to centile estimation.

A method for automatic selection of the smoothing parameters in a generalised additive model for location, scale and shape (GAMLSS) model is introduced. The method uses a P-spline representation of the smoothing terms to express them as random effect terms with an internal (or local) maximum likelihood estimation on the predictor scale of each distribution parameter to estimate its smoothing parameters. This provides a fast method for estimating multiple smoothing parameters.

B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells.

T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses.

CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation.

Effective vaccine adjuvants must induce expression of major histocompatibility (MHC) class II proteins and the costimulatory molecule CD86 on dendritic cells (DCs). However, some adjuvants elicit production of cytokines resulting in adverse inflammatory consequences. Development of agents that selectively increase MHC class II and CD86 expression without triggering unwanted cytokine production requires a better understanding of the molecular mechanisms influencing the production and degradation of MHC class II and CD86 in DCs.

IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses.

During T cell-dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in B cell growth, survival, and isotype switching.

Logic and extent of miRNA-mediated control of autoimmune gene expression.

Over the past few decades, multiple mechanisms have emerged that operate to prune the lymphocyte repertoire of self-reactive specificities and maintain immunological tolerance. Multiple families of small noncoding RNAs known as microRNAs (miRNAs) target immune transcripts to fine-tune gene expression and turn on negative feedback loops. Both of these actions are crucial to limit co-stimulation, set precise cellular activation thresholds, curtail inflammation, control lymphocyte growth, and maintain regulatory T cell homeostasis and suppressive function.

Estimating regional centile curves from mixed data sources and countries.

Regional or national growth distributions can provide vital information on the health status of populations. In most resource poor countries, however, the required anthropometric data from purpose-designed growth surveys are not readily available. We propose a practical method for estimating regional (multi-country) age-conditional weight distributions based on existing survey data from different countries.

Follicular helper T cells are required for systemic autoimmunity.

Production of high-affinity pathogenic autoantibodies appears to be central to the pathogenesis of lupus. Because normal high-affinity antibodies arise from germinal centers (GCs), aberrant selection of GC B cells, caused by either failure of negative selection or enhanced positive selection by follicular helper T (T(FH)) cells, is a plausible explanation for these autoantibodies. Mice homozygous for the san allele of Roquin, which encodes a RING-type ubiquitin ligase, develop GCs in the absence of foreign antigen, excessive T(FH) cell numbers, and features of lupus.

Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS.

During evolutionary adaptation in the immune system, host defense is traded off against autoreactivity. Signals through the costimulatory receptor CD28 enable T cells to respond specifically to pathogens, whereas those through the related costimulatory receptor, ICOS, which arose by gene duplication, are critical for affinity maturation and memory antibody responses. ICOS ligand, unlike the pathogen-inducible CD28 ligands, is widely and constitutively expressed in the immune system.

SiLEncing SLE: the power and promise of small noncoding RNAs.

Purpose Of Review: In this study, we outline the evidence suggesting that defects in the RNA silencing machinery can lead to the prototypic systemic autoimmune disease, systemic lupus erythematosus, and describe the potential for RNA interference to provide novel therapeutic agents.

Recent Findings: Over the last year, a class of small noncoding RNAs--microRNAs--have been shown to play key roles in immune regulation including T-cell selection in the thymus, B cell affinity maturation and selection in germinal centres, and development of regulatory T cells, suggesting that the microRNA machinery may be crucial in the maintenance of immunological tolerance. Two RNA silencing mechanisms have been shown to be involved in lupus pathogenesis: failed Roquin-mediated repression of inducible costimulatory receptors messenger RNA through miR-101 in roquin(san/san) mice and decreased expression of pro-apoptotic molecule and phosphatase and tensin homologue on chromosome 10 in mice transgenic for the miR-17-92 cluster, leading to lymphoproliferation and other lupus manisfestations.

Hyper IgE in New Zealand black mice due to a dominant-negative CD23 mutation.

Immunoglobulin E (IgE) plays a critical role in both resistance to parasitic infection and allergy to environmental antigens. The IgE response is in turn regulated by the B-cell co-receptor CD23, and CD23-deficient mice show exaggerated IgE responses and airway hyper-responsiveness. In this report, we show that New Zealand black (NZB) mice express a variant CD23 allele, with mutations in both the C-lectin-binding domain and stalk region, which fails to bind IgE at high affinity and has reduced expression on the cell surface.

Smooth centile curves for skew and kurtotic data modelled using the Box-Cox power exponential distribution.

The Box-Cox power exponential (BCPE) distribution, developed in this paper, provides a model for a dependent variable Y exhibiting both skewness and kurtosis (leptokurtosis or platykurtosis). The distribution is defined by a power transformation Y(nu) having a shifted and scaled (truncated) standard power exponential distribution with parameter tau. The distribution has four parameters and is denoted BCPE (mu,sigma,nu,tau).

Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity.

A novel locus regulates both retroviral glycoprotein 70 and anti-glycoprotein 70 antibody production in New Zealand mice when crossed with BALB/c.

Lupus-prone New Zealand Black and New Zealand White mice produce high serum levels of the endogenous retroviral envelope protein gp70 and develop an Ab response to this autoantigen as part of their autoimmune disease. Linkage analysis of two crosses involving New Zealand and BALB/c mice mapped these traits to a group of overlapping loci, including a novel locus on proximal chromosome 12. This locus was linked with serum gp70 and the autoimmune response against it.

New loci from New Zealand Black and New Zealand White mice on chromosomes 4 and 12 contribute to lupus-like disease in the context of BALB/c.

New Zealand Black (NZB) and New Zealand White (NZW) mice are genetically predisposed to a lupus-like autoimmune syndrome. To further define the loci linked to disease traits in NZB and NZW mice in the context of the BALB/c genetic background, linkage analyses were conducted in two crosses: (NZW x BALB/c.H2(z))F(1) x NZB and (NZB x BALB/c)F(2).