How small is too small? A systematic review of center volume and outcome after cardiac transplantation

Background—The aim of this study was to assess the relationship between the volume of cardiac transplantation procedures performed in a center and the outcome after cardiac transplantation. Methods and Results—PubMed, Embase, and the Cochrane library were searched for articles on the volume–outcome relationship in cardiac transplantation. Ten studies were identified, and all adopted a different approach to data analysis and varied in adjustment for baseline characteristics. The number of patients in each study ranged from 798 to 14401, and observed 1-year mortality ranged from 12.6% to 34%. There was no association between the continuous variables of center volume and observed mortality. There was a weak association between the continuous variables of center volume and adjusted mortality up to 1 year and a stronger association at 5 years. When centers were grouped in volume categories, low-volume centers had the highest adjusted mortality, intermediate-volume centers had lower adjusted mortality, and high-volume centers had the lowest adjusted mortality but were not significantly better than intermediate-volume centers. Category limits were arbitrary and varied between studies. Conclusions—There is a relationship between center volume and mortality in heart transplantation. The existence of a minimum acceptable center volume or threshold is unproven. However, a level of 10 to 12 heart transplants per year corresponds to the upper limit of low-volume categories that may have relatively higher mortality. It is not known whether outcomes for patients treated in low-volume transplant centers would be improved by reorganizing centers to ensure volumes in excess of 10 to 12 heart transplants per year

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

Background Exposure to metal working fluid (MWF) has been associated with outbreaks of EAA in the US, with bacterial contamination of MWF being a possible cause, but was uncommon in the UK. Twelve workers developed extrinsic allergic alveolitis (EAA) in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. This had three aims:- • To measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases. • To provide case-detection so that those affected can be treated. • To provide epidemiological data to identify the cause of the outbreak. Methods The outbreak was investigated in a three-phase cross-sectional survey of the workforce. Phase I A respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. Phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481(94.4%) responded along with 48/50(96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). Phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results 87 workers (10.4% of workforce) met case definitions for occupational lung disease, comprising EAA(19), occupational asthma(74) and humidifier fever(7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using metal working fluid (MWF) from a large sump(27.3%) compared with working all over the manufacturing area (7.9%) (OR=4.39,p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Conclusions Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF, there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance

Models of quintessence coupled to the electromagnetic field and the cosmological evolution of alpha

We study the change of the effective fine structure constant in the cosmological models of a scalar field with a non-vanishing coupling to the electromagnetic field. Combining cosmological data and terrestrial observations we place empirical constraints on the size of the possible coupling and explore a large class of models that exhibit tracking behavior. The change of the fine structure constant implied by the quasar absorption spectra together with the requirement of tracking behavior impose a lower bound of the size of this coupling. Furthermore, the transition to the quintessence regime implies a narrow window for this coupling around $10^{-5}$ in units of the inverse Planck mass. We also propose a non-minimal coupling between electromagnetism and quintessence which has the effect of leading only to changes of alpha determined from atomic physics phenomena, but leaving no observable consequences through nuclear physics effects. In doing so we are able to reconcile the claimed cosmological evidence for a changing fine structure constant with the tight constraints emerging from the Oklo natural nuclear reactor.Comment: 13 pages, 10 figures, RevTex, new references adde

Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors

OnlinePublAccurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.Nicole Dmochowska, Valentina Milanova, Ramesh Mukkamala, Kwok Keung Chow, Nguyen T. H. Pham, Madduri Srinivasarao, Lisa M. Ebert, Timothy Stait-Gardner, Hien Le, Anil Shetty, Melanie Nelson, Philip S. Low, and Benjamin Thierr

The role and importance of gene polymorphisms in the development of atherosclerosis

The development of atherosclerosis is a multifactorial process. The purpose of the study was to examine three genetic polymorphisms playing a role in the metabolic processes underlying the disease. We compared the data of 348 atherosclerotic non-diabetic patients with 260 atherosclerotic diabetic patients and 384 healthy controls. We analyzed the prevalence of myocardial infarction and stroke in three different groups of patients carrying different polymorphisms. It was proved that if the mutant TT eNOS Glu298ASP variant is present, a significantly higher number of myocardial infarctions can be observed than in patients carrying heterozygote GT or normal GG genotype. We proved that in the case of MTHFR 677CT heterozygote variants, the occurrence of myocardial infarction is significantly higher and the difference is also significant in case of the 677TT homozygote variant. It was verified that among patients with the mutant TNF-α AA genotype the occurrence of cardiovascular events was significantly higher. Screening the genetically high risk groups on the long run should be considered as an early detection opportunity that may give better chances for prevention and treatment. Understanding the inflammatory mechanisms of the atherosclerosis may give new therapeutical targets to pharmacologists

Transient Polycomb activity represses developmental genes in growing oocytes

Published online: 21 December 2022BACKGROUND: Non-genetic disease inheritance and offspring phenotype are substantially influenced by germline epigenetic programming, including genomic imprinting. Loss of Polycomb Repressive Complex 2 (PRC2) function in oocytes causes non-genetically inherited effects on offspring, including embryonic growth restriction followed by post-natal offspring overgrowth. While PRC2-dependent non-canonical imprinting is likely to contribute, less is known about germline epigenetic programming of non-imprinted genes during oocyte growth. In addition, de novo germline mutations in genes encoding PRC2 lead to overgrowth syndromes in human patients, but the extent to which PRC2 activity is conserved in human oocytes is poorly understood. RESULTS: In this study, we identify a discrete period of early oocyte growth during which PRC2 is expressed in mouse growing oocytes. Deletion of Eed during this window led to the de-repression of 343 genes. A high proportion of these were developmental regulators, and the vast majority were not imprinted genes. Many of the de-repressed genes were also marked by the PRC2-dependent epigenetic modification histone 3 lysine 27 trimethylation (H3K27me3) in primary-secondary mouse oocytes, at a time concurrent with PRC2 expression. In addition, we found H3K27me3 was also enriched on many of these genes by the germinal vesicle (GV) stage in human oocytes, strongly indicating that this PRC2 function is conserved in the human germline. However, while the 343 genes were de-repressed in mouse oocytes lacking EED, they were not de-repressed in pre-implantation embryos and lost H3K27me3 during pre-implantation development. This implies that H3K27me3 is a transient feature that represses a wide range of genes in oocytes. CONCLUSIONS: Together, these data indicate that EED has spatially and temporally distinct functions in the female germline to repress a wide range of developmentally important genes and that this activity is conserved in the mouse and human germlines.Ellen G. Jarred, Zhipeng Qu, Tesha Tsai, Ruby Oberin, Sigrid Petautschnig, Heidi Bildsoe, Stephen Pederson, Qing, hua Zhang, Jessica M. Stringer, John Carroll, David K. Gardner, Maarten Van den Buuse, Natalie A. Sims, William T. Gibson, David L. Adelson and Patrick S. Wester

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio