Intrahepatic bile duct strictures after human orthotopic liver transplantation - Recurrence of primary sclerosing cholangitis or unusual presentation of allograft rejection?

One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980-June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility. © 1988 Springer-Verlag

Determination of thermal conductivity of inhomogeneous orthotropic materials from temperature measurements

We consider the two-dimensional inverse determination of the thermal conductivity of inhomogeneous orthotropic materials from internal temperature measurements. The inverse problem is general and is classified as a function estimation since no prior information about the functional form of the thermal conductivity is assumed in the inverse calculation. The least-squares functional minimizing naturally the gap between the measured and computed temperature leads to a set of direct, sensitivity and adjoint problems, which have forms of direct well-posed initial boundary value problems for the heat equation, and new formulas for its gradients are derived. The conjugate gradient method employs recursively the solution of these problems at each iteration. Stopping the iterations according to the discrepancy principle criterion yields a stable solution. The employment of the Sobolev -gradient is shown to result in much more robust and accurate numerical reconstructions than when the standard -gradient is used

Independence and impartiality of sports disputes resolution in the UK

Private sports governing bodies in the United Kingdom have the contractual freedom to organise their own sports tribunals and disputes procedures. There is no legislation in the UK that governs the form of a sports governing body’s dispute resolution procedure. The common law and, to a certain extent, other industry measures influence the structure of a disputes procedure within a private sports governing body. When establishing dispute resolution systems in self-regulating industries, there is potential for structural conflicts of interest to arise. Reporting mechanisms and adjudicatory processes may be structurally bias through, for example, the way appointments are made to a dispute resolution panel. There may be the suggestion of implicit bias of panel members because of the interests that control the appointment process. Even if no actual bias arises, the perception of bias can damage the engagement of stakeholders in a dispute process and damage the reputation of the sport with sponsors or the general public. The key is to minimise structural conflicts of interest and ensure that the process is independent and impartial. This article examines the challenges faced with organising sports dispute resolution procedures, the requirements of Article 6 of the European Convention on Human Rights and highlights the important factors that a sports governing body should consider when designing an independent and impartial dispute resolution system. It concludes with a discussion of whether the legal basis for sports dispute resolution in the UK requires reconsideration to provide certainty, independence, impartiality and, above all, to guarantee a fair hearing

Image registration via stochastic gradient markov chain monte carlo

We develop a fully Bayesian framework for non-rigid registration of three-dimensional medical images, with a focus on uncertainty quantification. Probabilistic registration of large images along with calibrated uncertainty estimates is difficult for both computational and modelling reasons. To address the computational issues, we explore connections between the Markov chain Monte Carlo by backprop and the variational inference by backprop frameworks in order to efficiently draw thousands of samples from the posterior distribution. Regarding the modelling issues, we carefully design a Bayesian model for registration to overcome the existing barriers when using a dense, high-dimensional, and diffeomorphic parameterisation of the transformation. This results in improved calibration of uncertainty estimates

Pregnancy Outcomes in Women With Primary Adrenal Insufficiency: Data From a Multicentre Cohort Study

\ua9 2025 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.Objective: To determine characteristics and pregnancy outcomes in women with primary adrenal insufficiency (PAI). Design: Retrospective multicentre cohort study. Setting: Twenty-three maternity units in the UK and Ireland. Sample: Seventy-nine women with PAI who had 101 pregnancies. Method: Retrospective chart analysis. Main Outcome Measures: Adrenal crisis, pregnancy outcomes. Results: We obtained data on 101 pregnancies in 79 women with PAI. Most (51, 64.1%) had autoimmune disease, 8 (10.3%) had prior adrenal infarction/surgery/haemorrhage, 2 (2.6%) had congenital adrenal hyperplasia, and 18 (21.3%) were unclassified. 19 (24%) women experienced a crisis during pregnancy (18.8% of pregnancies). One woman died postpartum. Although all women had recorded endocrinology input during pregnancy, steroid emergency cards were only reportedly carried in 40 (39.6%) pregnancies and 9/19 (47.4%) of those with an adrenal crisis in pregnancy. Compared with the pre-pregnancy dose, only 41% of women received an increased hydrocortisone dose in pregnancy. The caesarean section rate was higher than the UK average: 62/97 (63.9%). The preterm birth rate was 21.2% (21/99) and 12.8% (12/94) of neonates had a birthweight < 10th centile. Conclusion: Whilst the obstetric outcome of pregnancy with PAI is generally favourable, there are high rates of caesarean birth and prematurity. A high number of women experienced adrenal crisis and further exploration is warranted. Recommendations regarding third trimester increases in hydrocortisone need consideration and potentially strengthening, in light of further evidence. Pregnant women with adrenal insufficiency should carry an NHS steroid warning card; this should be reinforced both by endocrine and obstetric teams because of the increased risk of life-threatening adrenal crisis

Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors

<p>Abstract</p> <p>Background</p> <p>We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers.</p> <p>Methods</p> <p>445 cases (35% of which were never smokers oversampled by design) between the ages of 20-84 were identified through four major tertiary care hospitals in metropolitan Toronto between 1997 and 2002 and were frequency matched on sex and ethnicity with 425 population controls and 523 hospital controls. Unconditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between exposures and lung cancer risk.</p> <p>Results</p> <p>Any previous exposure to occupational exposures (OR total population 1.6, 95% CI 1.4-2.1, OR never smokers 2.1, 95% CI 1.3-3.3), a previous diagnosis of emphysema in the total population (OR 4.8, 95% CI 2.0-11.1) or a first degree family member with a previous cancer diagnosis before age 50 among never smokers (OR 1.8, 95% CI 1.0-3.2) were associated with increased lung cancer risk.</p> <p>Conclusions</p> <p>Occupational exposures and family history of cancer with young onset were important risk factors among never smokers.</p

Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites

Background: We have previously described an approach to predicting the substrate specificity of serine-threonine protein kinases. The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. Predikin was implemented originally as a web application written in Javascript

Pretransplant Prediction of Posttransplant Survival for Liver Recipients with Benign End-Stage Liver Diseases: A Nonlinear Model

Background: The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients ’ survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a generalillness severity model (the sequential organ failure assessment score, or SOFA score). Methodology/Principal Findings: With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na +; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, wit

Influenza Virus-Like Particles Containing M2 Induce Broadly Cross Protective Immunity

Current influenza vaccines based on the hemagglutinin protein are strain specific and do not provide good protection against drifted viruses or emergence of new pandemic strains. An influenza vaccine that can confer cross-protection against antigenically different influenza A strains is highly desirable for improving public health.To develop a cross protective vaccine, we generated influenza virus-like particles containing the highly conserved M2 protein in a membrane-anchored form (M2 VLPs), and investigated their immunogenicity and breadth of cross protection. Immunization of mice with M2 VLPs induced anti-M2 antibodies binding to virions of various strains, M2 specific T cell responses, and conferred long-lasting cross protection against heterologous and heterosubtypic influenza viruses. M2 immune sera were found to play an important role in providing cross protection against heterosubtypic virus and an antigenically distinct 2009 pandemic H1N1 virus, and depletion of dendritic and macrophage cells abolished this cross protection, providing new insight into cross-protective immune mechanisms.These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines

Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

BACKGROUND: Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. PRESENTATION: We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. IMPLICATIONS: We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. TESTING: Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis