Brief review on systematic hypothermia for the protection of central nervous system during aortic arch surgery: a double-sword tool?

Antegrade selective cerebral perfusion in conjunction with hypothermia attenuate postoperative neurological injury, which in turn still remains the main cause of mortality and morbidity following aortic arch surgery. Hypothermic circulatory arrest however could be a useful tool during arch surgery, surgery for chronic thromboembolic disease, air on the arterial line during CPB, during cavotomy for extraction of renal cell carcinoma with level IV extension, or when dealing with difficult trauma to the SVC or IVC. Cerebral protective effects with hypothermic procedures including inhibition of neuron excitation, and discharge of excitable amino acids, and thereby, prevention of an increase in intercellular calcium ions, hyperoxidation of lipids in cell membranes, and free radical production

Mineral dust increases the habitability of terrestrial planets but confounds biomarker detection

Identification of habitable planets beyond our solar system is a key goal of current and future space missions. Yet habitability depends not only on the stellar irradiance, but equally on constituent parts of the planetary atmosphere. Here we show, for the first time, that radiatively active mineral dust will have a significant impact on the habitability of Earth-like exoplanets. On tidally-locked planets, dust cools the day-side and warms the night-side, significantly widening the habitable zone. Independent of orbital configuration, we suggest that airborne dust can postpone planetary water loss at the inner edge of the habitable zone, through a feedback involving decreasing ocean coverage and increased dust loading. The inclusion of dust significantly obscures key biomarker gases (e.g. ozone, methane) in simulated transmission spectra, implying an important influence on the interpretation of observations.We demonstrate that future observational and theoretical studies of terrestrial exoplanets must consider the effect of dust

B cell depletion in autoimmune diabetes:insights from murine models

INTRODUCTION: The incidence of type 1 diabetes (T1D) is rising for reasons that largely elude us. New strategies aimed at halting the disease process are needed. One type of immune cell thought to contribute to T1D is the B lymphocyte. The first Phase II trial of B cell depletion in new onset T1D patients indicated that this slowed the destruction of insulin-producing pancreatic beta cells. The mechanistic basis of the beneficial effects remains unclear. AREAS COVERED: Studies of B cell depletion and deficiency in animal models of T1D. How B cells can influence T cell-dependent autoimmune diabetes in animal models. The heterogeneity of B cell populations and current evidence for the potential contribution of specific B cell subsets to diabetes, with emphasis on marginal zone B cells and B1 B cells. EXPERT OPINION: B cells can influence the T cell response to islet antigens and B cell depletion or genetic deficiency is associated with decreased insulitis in animal models. New evidence suggests that B1 cells may contribute to diabetes pathogenesis. A better understanding of the roles of individual B cell subsets in disease will permit fine-tuning of therapeutic strategies to modify these populations

Modelling Survival and Mortality Risk to 15 Years of Age for a National Cohort of Children with Serious Congenital Heart Defects Diagnosed in Infancy

Congenital heart defects (CHDs) are a significant cause of death in infancy. Although contemporary management ensures that 80% of affected children reach adulthood, post-infant mortality and factors associated with death during childhood are not well-characterised. Using data from a UK-wide multicentre birth cohort of children with serious CHDs, we observed survival and investigated independent predictors of mortality up to age 15 years. Methods Data were extracted retrospectively from hospital records and death certificates of 3,897 children (57% boys) in a prospectively identified cohort, born 1992–1995 with CHDs requiring intervention or resulting in death before age one year. A discrete-time survival model accounted for time-varying predictors; hazards ratios were estimated for mortality. Incomplete data were addressed through multilevel multiple imputation. Findings By age 15 years, 932 children had died; 144 died without any procedure. Survival to one year was 79.8% (95% confidence intervals [CI] 78.5, 81.1%) and to 15 years was 71.7% (63.9, 73.4%), with variation by cardiac diagnosis. Importantly, 20% of cohort deaths occurred after age one year. Models using imputed data (including all children from birth) demonstrated higher mortality risk as independently associated with cardiac diagnosis, female sex, preterm birth, having additional cardiac defects or non-cardiac malformations. In models excluding children who had no procedure, additional predictors of higher mortality were younger age at first procedure, lower weight or height, longer cardiopulmonary bypass or circulatory arrest duration, and peri-procedural complications; non-cardiac malformations were no longer significant. Interpretation We confirm the high mortality risk associated with CHDs in the first year of life and demonstrate an important persisting risk of death throughout childhood. Late mortality may be underestimated by procedure-based audit focusing on shorter-term surgical outcomes. National monitoring systems should emphasise the importance of routinely capturing longer-term survival and exploring the mechanismsThis work was supported by a British Heart Foundation project grant (reference PG/02/065/13934). RLK was awarded an MRC Special Training Fellowship in Health of the Public and Health Services Research (reference G106/1083). HG and the Centre for Paediatric Epidemiology and Biostatistics benefited from Medical Research Council funding support to the MRC Centre of Epidemiology for Child Health (reference G04005546). Great Ormond St Hospital for Children NHS Trust and the UCL Institute of Child Health receives a proportion of funding from the Department of Health's NIHR Biomedical Research Centres schem