Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure

This paper is funded by an MRC/EPSRC Discipline Bridging Initiative Grant (G0502256-77947) to W. Wan

Safety aspects of infliximab in inflammatory bowel disease patients - A retrospective cohort study in 100 patients of a German University Hospital

Background: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. Methods: 100 patients with severe Crohn's disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. Results: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. Conclusion: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab. Copyright (C) 2004 S. Karger AG, Basel

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Computing the vertices of tropical polyhedra using directed hypergraphs

We establish a characterization of the vertices of a tropical polyhedron defined as the intersection of finitely many half-spaces. We show that a point is a vertex if, and only if, a directed hypergraph, constructed from the subdifferentials of the active constraints at this point, admits a unique strongly connected component that is maximal with respect to the reachability relation (all the other strongly connected components have access to it). This property can be checked in almost linear-time. This allows us to develop a tropical analogue of the classical double description method, which computes a minimal internal representation (in terms of vertices) of a polyhedron defined externally (by half-spaces or hyperplanes). We provide theoretical worst case complexity bounds and report extensive experimental tests performed using the library TPLib, showing that this method outperforms the other existing approaches.Comment: 29 pages (A4), 10 figures, 1 table; v2: Improved algorithm in section 5 (using directed hypergraphs), detailed appendix; v3: major revision of the article (adding tropical hyperplanes, alternative method by arrangements, etc); v4: minor revisio

Impaired Competence for Pretense in Children with Autism: Exploring Potential Cognitive Predictors.

Lack of pretense in children with autism has been explained by a number of theoretical explanations, including impaired mentalising, impaired response inhibition, and weak central coherence. This study aimed to empirically test each of these theories. Children with autism (n=60) were significantly impaired relative to controls (n=65) when interpreting pretense, thereby supporting a competence deficit hypothesis. They also showed impaired mentalising and response inhibition, but superior local processing indicating weak central coherence. Regression analyses revealed that mentalising significantly and independently predicted pretense. The results are interpreted as supporting the impaired mentalising theory and evidence against competing theories invoking impaired response inhibition or a local processing bias. The results of this study have important implications for treatment and intervention

Variation in plasma oxidative status and testosterone level in relation to egg-eviction effort and age of brood-parasitic common cuckoo nestlings

To avoid competition for parental care, brood-parasitic Common Cuckoo (Cuculus canorus) nestlings evict all of the host's eggs and nestlings within a few days after hatching. Little is known about the physiological effects of eviction behavior on the cuckoo nestling's oxidative balance or about age-related variation in plasma oxidative status and testosterone level of developing birds. We examined whether the cuckoo nestling's plasma oxidative status was related to prior effort in eviction and quantified variation in the level of reactive oxygen metabolites, of nonenzymatic antioxidant capacity, and of testosterone concentration in plasma at various phases of the cuckoo's development. Levels of both reactive oxygen metabolites and antioxidant capacity were greater in older than in younger nestlings, suggesting that younger nestlings effectively counterbalance their increased production of free radicals, whereas, near fledging, levels of reactive oxygen metabolites increase despite improved antioxidant capacity. Possibly, overall energy expenditure increases with age and elevates the production of reactive oxygen species to a rate higher than what the antioxidant system could eliminate. Plasma testosterone level was the highest at nestlings' intermediate phase of growth. High levels of testosterone may be required during the period of fastest growth, and when the growth rate levels off near fledging, testosterone levels may also decline. Cuckoo chicks that evicted more host eggs from steeper nests had higher plasma levels of reactive oxygen metabolites shortly after the eviction period, suggesting that eviction is costly in terms of an increased level of oxidative stress. Para evitar la competencia por el cuidado parental, los polluelos parásitos de nidada de Cuculus canorus desalojan todos los huevos y los polluelos del hospedador a los pocos días después de la eclosión. Se sabe poco sobre los efectos fisiológicos del comportamiento de desalojo en el balance oxidativo de los polluelos de C. canorus o sobre la variación en el estatus oxidativo del plasma y el nivel de testosterona relacionado con la edad de las aves en desarrollo. Examinamos si el estatus oxidativo del plasma de los polluelos de C. canorus se relacionaba con un esfuerzo previo de desalojo y cuantificamos la variación en el nivel de metabolitos reactivos de oxígeno, la capacidad antioxidante no enzimática y la concentración de testosterona en el plasma en varias fases del desarrollo de C. canorus. Tanto los niveles de metabolitos reactivos de oxígeno como la capacidad antioxidante fueron superiores en los polluelos de mayor edad que en los más jóvenes, lo que sugiere que los polluelos de menor edad contrarrestan eficazmente el aumento de la producción de radicales libres, mientras que, cuando se apróximan al abandono del nido, los niveles de metabolitos reactivos de oxígeno aumentan a pesar de una mejora en la capacidad antioxidante. Posiblemente, el gasto total de energía se incrementa con la edad, elevándose la producción de formas reactivas de oxígeno a una tasa mayor de la que el sistema antioxidante puede eliminar. El nivel de testosterona en el plasma fue máximo en la fase intermedia del crecimiento de los polluelos. Pueden requerirse altos niveles de testosterona durante el período de mayor crecimiento y, cuando la tasa de crecimiento se estabiliza cerca del abandono del nido, los niveles de testosterona también podrián disminuir. Los polluelos de C. canorus que desalojaron más huevos del hospedador en nidos con una estructura más empinada tuvieron niveles de plasma de metabolitos reactivos de oxígeno en plasma más altos poco después del período de desalojo, sugiriendo que el desalojo es costoso en términos de un incremento en el nivel de estrés oxidativo

Measuring Empathizing and Systemizing with a Large US Sample

A large number of people completed one of two versions of the empathizing quotient (EQ) and systemizing quotient (SQ). One version had the negatively phrased items all re-worded. These re-worded items were answered more rapidly than the original items, and for the SQ produced a more reliable scale. Subjects gave self-assessments of empathizing and systemizing, and these were moderately correlated, r≈.6, with their respective quotients. Females had on average higher empathizing scores and males had on average higher systemizing scores. If a female-male pair was chosen at random, the female would have the higher empathizing score about two-thirds of the time, and the males would have the higher systemizing score about two-thirds of the time

Social networks and labour productivity in Europe: An empirical investigation

This paper uses firm-level data recorded in the AMADEUS database to investigate the distribution of labour productivity in different European countries. We find that the upper tail of the empirical productivity distributions follows a decaying power-law, whose exponent $\alpha$ is obtained by a semi-parametric estimation technique recently developed by Clementi et al. (2006). The emergence of "fat tails" in productivity distribution has already been detected in Di Matteo et al. (2005) and explained by means of a model of social network. Here we show that this model is tested on a broader sample of countries having different patterns of social network structure. These different social attitudes, measured using a social capital indicator, reflect in the power-law exponent estimates, verifying in this way the existence of linkages among firms' productivity performance and social network.Comment: LaTeX2e; 18 pages with 3 figures; Journal of Economic Interaction and Coordination, in pres

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

Rhabdomyolysis and Acute Renal Failure After Fire Ant Bites

We describe a 59-year-old patient who developed acute renal failure because of rhabdomyolysis after extensive red fire ant bites. This case illustrates a serious systemic reaction that may occur from fire ant bites. Consistent with the clinical presentation in rhabdomyolysis associated with non-traumatic causes, hyperkalemia, hypophosphatemia, hypocalcemia, and high anion gap acidosis were not observed in this patient. While local allergic reactions to fire ant bites are described in the literature, serious systemic complications with rhabdomyolysis and renal failure have not been previously reported. It is our effort to alert the medical community of the possibility of such a complication that can occur in the victims of fire ant bites