Solving difficult hepatobiliary problems in children

Most difficult hepatobiliary (HPB) problems in infancy and childhood result from pathological anatomical/mechanical derangements; therefore, surgery on the liver and bile ducts depends on a detailed understanding of liver structure, function and repair response to injury or disease. The surgeon must be aware of the very diverse range of anatomical variations. Perhaps key to improving the outcome of paediatric HPB surgery is centralised management and associating this with a paediatric liver transplant programme, which adds expertise and, frequently, the added benefit of adult HPB surgical input to paediatric surgical care. In the United Kingdom, this has resulted in excellent measurable benefit, particularly in the management of biliary atresia, but also of choledochal cysts, portal hypertension and liver tumours. These conditions are briefly discussed here, with focus on the technical aspects of operative management

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Patterns of pediatric injury in South Africa: An analysis of hospital data between 1997 and 2006

BACKGROUND: Pediatric injuries are associated with significant morbidity and mortality, especially in low- and middle-income countries. Despite the magnitude of this burden, there is lack of data to characterize the etiology and risk factors associated with childhood injuries, especially in low- and middle-income countries. The aim of this article is to describe the demographics, mechanisms, and severity of injuries during a 10-year time period using hospital-based data in Cape Town, South Africa. METHODS: Data from Childsafe South Africa\u27s registry were used to study injured children younger than 13 years who presented with either intentional or unintentional injuries to the Trauma Unit of the Red Cross War Memorial Children\u27s Hospital\u27s (RCH) Causality Department between 1996 and 2007. Univariate and bivariate analyses were performed for demographic characteristics and injury mechanisms. Poisson regression analysis was used to analyze the age-adjusted annual incidence of injury presenting to RCH. RESULTS: Between 1997 and 2006, 62,782 children with a total of 68,883 injuries presented to RCH. The mean age was 5.4 years (standard deviation ± 3.5 years) and 61.7% were male. Mechanism of injury included falls (39.8%), road traffic injuries (15.7%), burns (8.8%), and assault (7.4%). The majority of injuries occurred in and around the home. Abbreviated injury severity scoring showed 60.2% of injuries were minor, 36.6% were moderate, and 3.2% were severe. Sixty-six deaths occurred in the trauma casualty department. Thirty-one percent of patients were admitted to the hospital; children who suffered burn and head injuries were more likely to require admission. CONCLUSION: Age, gender, mechanism, and severity of injury in pediatric populations have not been described elsewhere in South African national or sub-Saharan regional data. This retrospective, observational study uses Level II evidence to suggest the need for targeted interventions to address risk factors for pediatric injuries, emphasizing the importance of pediatric surveillance systems as a tool to study injuries in developing countries. LEVEL OF EVIDENCE: Prognostic study, level II. Copyright © 2012 Lippincott Williams & Wilkins

Changing state of pediatric injuries in South Africa: An analysis of surveillance data from a Pediatric Emergency Department from 2007 to 2011

© 2017 Elsevier Inc. Background Pediatric injuries are associated with significant morbidity and mortality, especially in low- and middle-income countries. Data to characterize the cause and risk factors associated with childhood injuries in low- and middle-income countries are very scarce. The aim of this study is to describe the cause of pediatric injuries and their possible changes between 2007 and 2011 using hospital-based data in Cape Town, South Africa. Methods Data from injured children \u3c13 years of age who presented to the Red Cross War Memorial Children\u27s Hospital\u27s emergency department in 2007 and 2011 were captured in Childsafe South Africa\u27s trauma surveillance system. Poisson regression was used to assess changes in rates of injury between 2007 and 2011 in terms of demographics, geographic location of injury, type of injury mechanism, injury severity, and anatomic region of the sustained injury. Results In total, 14,915 injured children with 15,414 injuries presented to Red Cross War Memorial Children\u27s Hospital in 2007 and 2011. The mean age was 5.01 ± 3.5 years and 60.3% were male. Common mechanisms of injury included falls (n = 6,036; 40%), road traffic injuries (n = 1,939; 13%), burns (n = 1,885; 12.6%), and assault (n = 640; 4.3%). Comparing 2011 to 2007, the incidence of road traffic injuries has decreased by 7% (P \u3c.05) while burn injuries increased 11% (P \u3c.05). Seventy-three percent (73%) of injuries that presented to Red Cross War Memorial Children\u27s Hospital occurred in the Cape Flats area of Cape Town, where many informal settlements exist. Conclusion These epidemiologic findings suggest that while road traffic injuries decreased and burn injuries increased at Red Cross War Memorial Children\u27s Hospital, there is a need for data that are population-based and not hospital based. If we could describe injuries accurately within the pediatric population of a city such as Cape Town, we could in turn use this data to strengthen the need for targeted interventions to address risk factors for pediatric injuries. Despite this, hospital-based data remain a powerful tool to study injuries in low and middle-income countries

Pediatric burn injuries in South Africa: A 15-year analysis of hospital data

Introduction: Burns are a significant burden of pediatric injuries, particularly in low and middle-income countries, were more than 90% of burn-related pediatric deaths occur. This study explores pediatric burn-related injuries over a fifteen year time period in South Africa through an analysis of a pediatric trauma surveillance system. Methods: This retrospective observational study used data collected by Childsafe South Africa from the Red Cross War Memorial Children\u27s Hospital (RCH) trauma registry in Cape Town, South Africa between 1995 and 2009 for children less than 13 years of age who presented with burn injuries to the hospital\u27s casualty department. Demographic data and Abbreviated Injury Scores (AISs) were first assessed, followed by an analysis of time trends using Poisson regression. Logistic regression models were used to analyse factors related to hospital admissions. Results: Between 1995 and 2009, 9438 children with burn-related injuries presented to RCH, of which nearly three-quarters resulted from scalds (73%; n = 7024). The mean age of the injured children was 3.1 ± 2.9 years 58% were male. 11 deaths occurred in the hospital\u27s casualty department. 39% of injuries were minor, 56% were moderate, and 5% were severe. During the 15-year study period, moderate burn injuries increased by 3%, while minor injuries decreased by 10% (p \u3c 0.05). 49% of all children were admitted to the hospital. Hospital admissions increased by 3% (p \u3c 0.05) during the study period. Conclusions: Pediatric burn injuries are a significant contributor to the burden of child diseases in developing county hospitals. Pediatric surveillance systems, such as Childsafe South Africa\u27s, are important to study epidemiologic changes in burn injuries. Findings suggest the need for targeted interventions to address the prevention of specific burn-related injuries. © 2013 Published by Elsevier Ltd

Measurements of ttˉt\bar{t} differential cross-sections of highly boosted top quarks decaying to all-hadronic final states in pppp collisions at s=13 \sqrt{s}=13\, TeV using the ATLAS detector

Measurements are made of differential cross-sections of highly boosted pair-produced top quarks as a function of top-quark and $t\bar{t}$ system kinematic observables using proton--proton collisions at a center-of-mass energy of $\sqrt{s} = 13$ TeV. The data set corresponds to an integrated luminosity of $36.1$ fb$^{-1}$, recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. Events with two large-radius jets in the final state, one with transverse momentum $p_{\rm T} > 500$ GeV and a second with $p_{\rm T}>350$ GeV, are used for the measurement. The top-quark candidates are separated from the multijet background using jet substructure information and association with a $b$-tagged jet. The measured spectra are corrected for detector effects to a particle-level fiducial phase space and a parton-level limited phase space, and are compared to several Monte Carlo simulations by means of calculated $\chi^2$ values. The cross-section for $t\bar{t}$ production in the fiducial phase-space region is $292 \pm 7 \ \rm{(stat)} \pm 76 \rm{(syst)}$ fb, to be compared to the theoretical prediction of $384 \pm 36$ fb

Measurements of ttˉt\bar{t} differential cross-sections of highly boosted top quarks decaying to all-hadronic final states in pppp collisions at s=13 \sqrt{s}=13\, TeV using the ATLAS detector

Measurements are made of differential cross-sections of highly boosted pair-produced top quarks as a function of top-quark and $t\bar{t}$ system kinematic observables using proton--proton collisions at a center-of-mass energy of $\sqrt{s} = 13$ TeV. The data set corresponds to an integrated luminosity of $36.1$ fb$^{-1}$, recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. Events with two large-radius jets in the final state, one with transverse momentum $p_{\rm T} > 500$ GeV and a second with $p_{\rm T}>350$ GeV, are used for the measurement. The top-quark candidates are separated from the multijet background using jet substructure information and association with a $b$-tagged jet. The measured spectra are corrected for detector effects to a particle-level fiducial phase space and a parton-level limited phase space, and are compared to several Monte Carlo simulations by means of calculated $\chi^2$ values. The cross-section for $t\bar{t}$ production in the fiducial phase-space region is $292 \pm 7 \ \rm{(stat)} \pm 76 \rm{(syst)}$ fb, to be compared to the theoretical prediction of $384 \pm 36$ fb

Search for direct top squark pair production in final states with two leptons in s=13\sqrt{s} = 13 TeV pppp collisions with the ATLAS detector

International audienceThe results of a search for direct pair production of top squarks in events with two opposite-charge leptons (electrons or muons) are reported, using $36.1~\hbox {fb}^{-1}$ of integrated luminosity from proton–proton collisions at $\sqrt{s}=13$ TeV collected by the ATLAS detector at the Large Hadron Collider. To cover a range of mass differences between the top squark $\tilde{t}$ and lighter supersymmetric particles, four possible decay modes of the top squark are targeted with dedicated selections: the decay $\tilde{t} \rightarrow b \tilde{\chi }_{1}^{\pm }$ into a b-quark and the lightest chargino with $\tilde{\chi }_{1}^{\pm } \rightarrow W \tilde{\chi }_{1}^{0}$ , the decay $\tilde{t} \rightarrow t \tilde{\chi }_{1}^{0}$ into an on-shell top quark and the lightest neutralino, the three-body decay $\tilde{t} \rightarrow b W \tilde{\chi }_{1}^{0}$ and the four-body decay $\tilde{t} \rightarrow b \ell \nu \tilde{\chi }_{1}^{0}$ . No significant excess of events is observed above the Standard Model background for any selection, and limits on top squarks are set as a function of the $\tilde{t}$ and $\tilde{\chi }_{1}^{0}$ masses. The results exclude at 95% confidence level $\tilde{t}$ masses up to about 720 GeV, extending the exclusion region of supersymmetric parameter space covered by previous searches

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease