tbuckley/cabot-search huggingface dataset:
Thoracic surgery and lung transplantation: Thoracic Surgery Assembly contribution to the celebration of 20 years of the ERS
Authors: E. Canalís, A. Boehler, D. Subotic
Journal: European Respiratory Journal (2010)

When two pre-existing European respiratory societies (the Societas Europaea Physiologiae Clinicae Respoiratoriae (SEPCR) and the European Society of Pneumology (SEP)) merged 20 years ago to form the European Respiratory Society (ERS) 1, the Thoracic Surgery Assembly was established within the new Society. The foundation of our Assembly was the result of founder pneumologists’ and thoracic surgeons’ conviction of the need for collaboration between these two medical specialties. Such collaboration occurs in everyday work and, indeed, our community is enriched when our efforts are combined to form a wider spectrum of scientific knowledge 2.

In preparation for this Editorial, we conducted an informal survey of colleagues from different countries and from teaching, research and clinical backgrounds in thoracic surgery, and asked them how the specialty is considered, taught and organised in their country. We asked about training in thoracic surgery (whether there is a specific training programme, whether training is provided after general surgery or combined with cardiac surgery, and how trainees can enter residency programmes), working in the specialty at a professional level (time taken to gain a position after the residency period, excess or lack of specialists, and possible conflict with other surgical specialties), and finally about national and European scientific societies (whether they are only for general thoracic surgeons or shared with other specialties like pneumology, general surgery or cardiac surgery).

As a result of our colleagues’ responses, we can separate thoracic surgery in Europe into three different categories: Northern Europe (including Scandinavia, Germany, the UK and France); Eastern Europe (Russia and the Newly Independent States); Southern Europe (including Spain, Italy, Serbia and Greece). Each category has distinct features in terms of training, performance and collaboration in thoracic surgery, as follows.

Northern Europe: In Northern Europe, training in thoracic surgery is combined with cardiac surgery (with …
A Validated Mathematical Model of Cell-Mediated Immune Response to Tumor Growth
Authors: Lisette G. de Pillis, Ami E. Radunskaya, Charles L. Wiseman
Journal: Cancer Research (2005)

Abstract Mathematical models of tumor-immune interactions provide an analytic framework in which to address specific questions about tumor-immune dynamics. We present a new mathematical model that describes tumor-immune interactions, focusing on the role of natural killer (NK) and CD8+ T cells in tumor surveillance, with the goal of understanding the dynamics of immune-mediated tumor rejection. The model describes tumor-immune cell interactions using a system of differential equations. The functions describing tumor-immune growth, response, and interaction rates, as well as associated variables, are developed using a least-squares method combined with a numerical differential equations solver. Parameter estimates and model validations use data from published mouse and human studies. Specifically, CD8+ T-tumor and NK-tumor lysis data from chromium release assays as well as in vivo tumor growth data are used. A variable sensitivity analysis is done on the model. The new functional forms developed show that there is a clear distinction between the dynamics of NK and CD8+ T cells. Simulations of tumor growth using different levels of immune stimulating ligands, effector cells, and tumor challenge are able to reproduce data from the published studies. A sensitivity analysis reveals that the variable to which the model is most sensitive is patient specific, and can be measured with a chromium release assay. The variable sensitivity analysis suggests that the model can predict which patients may positively respond to treatment. Computer simulations highlight the importance of CD8+ T-cell activation in cancer therapy.
Differential regulation of human and murine P-selectin expression and function in vivo
Authors: Zhenghui Liu, Jonathan J. Miner, Tadayuki Yago, Longbiao Yao, Florea Lupu, Lijun Xia, Rodger P. McEver
Journal: The Journal of Experimental Medicine (2010)

Leukocytes roll on P-selectin after its mobilization from secretory granules to the surfaces of platelets and endothelial cells. Tumor necrosis factor (TNF), IL-1β, and lipopolysaccharide increase synthesis of P-selectin in murine but not in human endothelial cells. To explore the physiological significance of this difference in gene regulation, we made transgenic mice bearing the human Selp gene and crossed them with mice lacking murine P-selectin (Selp−/−). The transgenic mice constitutively expressed human P-selectin in platelets, endothelial cells, and macrophages. P-selectin mediated comparable neutrophil migration into the inflamed peritoneum of transgenic and wild-type (WT) mice. Leukocytes rolled similarly on human or murine P-selectin on activated murine platelets and in venules of the cremaster muscle subjected to trauma. However, TNF increased murine P-selectin in venules, slowing rolling and increasing adhesion, whereas it decreased human P-selectin, accelerating rolling and decreasing adhesion. Both P- and E-selectin mediated basal rolling in the skin of WT mice, but E-selectin dominated rolling in transgenic mice. During contact hypersensitivity, murine P-selectin messenger (m) RNA was up-regulated and P-selectin was essential for leukocyte recruitment. However, human P-selectin mRNA was down-regulated and P-selectin contributed much less to leukocyte recruitment. These findings reveal functionally significant differences in basal and inducible expression of human and murine P-selectin in vivo.
Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis
Authors: M Carlson
Journal: Gut (2002)

Background and aim: Accumulation and infiltration by neutrophil granulocytes is a prominent feature in the local inflammatory process in ulcerative colitis (UC). The present study was performed to evaluate human neutrophil lipocalin (HNL) as a specific neutrophil marker in the inflamed lesions of the colon and rectum in patients with colitis and proctitis. Methods: The activity of intestinal neutrophils with respect to release of granule proteins was studied in 18 patients with UC (10 with colitis and eight with isolated proctitis) and in 18 healthy controls using perfusion fluid and biopsies from the sigmoid colon and rectum. The released amounts of the neutrophil granule proteins HNL and myeloperoxidase (MPO) were determined by radioimmunoassays, and the location of HNL and MPO in biopsies from colonic mucosa was examined by immunohistochemistry. Results: Mucosal release of HNL and MPO was increased 10–55-fold in patients with colitis and proctitis compared with controls. Their bowel biopsies demonstrated that only neutrophils were stained with anti-HNL. We also found correlations between HNL and levels of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8) in perfusion fluids from the sigmoidal segments of patients with proctitis, between HNL and GM-CSF in rectal segments in patients with proctitis, and in sigmoidal segments in patients with colitis. Conclusion: We conclude that the increased release of HNL and MPO in colorectal perfusion fluids indicates neutrophil involvement in the local inflammatory process, and suggest that HNL may serve as a specific marker of intestinal neutrophil activation in UC. GM-CSF, and to some extent IL-8, may play a role in neutrophil accumulation and priming in this disease.
Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data
Authors: Philip Bejon, Michael T White, Ally Olotu, Kalifa Bojang, John PA Lusingu, Nahya Salim, Nekoye N Otsyula, Selidji T Agnandji, Kwaku Poku Asante, Seth Owusu-Agyei, Salim Abdulla, Azra C Ghani
Journal: The Lancet Infectious Diseases (2013)

The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data.We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2-10 years (PrP₂₋₁₀), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02.Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP₂₋₁₀ 20%) it was 41% (21 to 57), and at high transmission (PrP₂₋₁₀ 70%) the efficacy was 4% (-10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)--eg, at low transmission (PrP₂₋₁₀ 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (-38 to 38) after 3 years.Vaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination.Medical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust.
Binding of proteolytically-degraded human colonic mucin glycoproteins to the Gal/GalNAc adherence lectin of Entamoeba histolytica.
Authors: K Chadee, C Ndarathi, K Keller
Journal: Gut (1990)

Rat and human colonic mucin glycoproteins bind to the Gal/GalNAc adherence lectin on the surface of Entamoeba histolytica in vitro, thus inhibiting the organism from adhering to and lysing the target cells. Human colonic mucin glycoproteins were isolated by Sepharose 4B gel filtration chromatography, they were proteolytically degraded with trypsin, pronase, and papain, and the glycoprotein fractions were reisolated by Sephacryl S-200 gel filtration chromatography. Binding of the mucin glycoprotein fractions to amoebae was quantitated by the inhibition of adherence of Chinese hamster ovary cells to the surface of the amoebae. Trypsin and papain digests caused 40 and 20% reductions, respectively, in the excluded fractions (void volume) that contained all the carbohydrates; pronase digests resulted in extensive degradation of the mucin glycoprotein with the carbohydrate fractions eluting over 40% of the gel bed volume. 3H-labelled mucin glycoprotein and sodium dodecylsulfate-polyacrylamide gel electrophoresis confirmed the presence of the high molecular weight carbohydrate-rich glycoproteins with no subunits in the excluded fractions and the absence of sugars in the included peptides. Only the high molecular weight carbohydrate-containing fractions bind amoebae and inhibit amoebic adherence to Chinese hamster ovary cells. The trypsin digested mucins in the excluded volume were more efficient than the native undigested mucins in binding amoebae. The carbohydrate-containing fractions of the pronase digests were the least effective in binding amoebae and inhibiting adherence of Chinese hamster ovary cells. This suggests that proteolytically-degraded colonic mucins that are glycosylated, as well as the undegraded native mucin glycoproteins of the gut, may play a protective role in binding to amoebae, thus preventing contact of amoebae with mucosal epithelial cells and potential invasion.
An observational method to code concussions in the National Hockey League (NHL): the heads-up checklist
Authors: Michael G Hutchison, Paul Comper, Willem H Meeuwisse, Ruben J Echemendia
Journal: British Journal of Sports Medicine (2013)

Development of effective strategies for preventing concussions is a priority in all sports, including ice hockey. Digital video records of sports events contain a rich source of valuable information, and are therefore a promising resource for analysing situational factors and injury mechanisms related to concussion.To determine whether independent raters reliably agreed on the antecedent events and mechanisms of injury when using a standardised observational tool known as the heads-up checklist (HUC) to code digital video records of concussions in the National Hockey League (NHL).The study occurred in two phases. In phase 1, four raters (2 naïve and 2 expert) independently viewed and completed HUCs for 25 video records of NHL concussions randomly chosen from the pool of concussion events from the 2006-2007 regular season. Following initial analysis, three additional factors were added to the HUC, resulting in a total of 17 factors of interest. Two expert raters then viewed the remaining concussion events from the 2006-2007 season, as well as all digital video records of concussion events up to 31 December 2009 (n=174).For phase 1, the majority of the factors had a κ value of 0.6 or higher (8 of 15 factors for naïve raters; 11 of 15 factors for expert raters). For phase 2, all the factors had a total percent agreement value greater than 0.8 and κ values of >0.65 for the expert raters.HUC is an objective, reliable tool for coding the antecedent events and mechanisms of concussions in the NHL.
Standardised criteria for ECG interpretation in athletes: a practical tool
Authors: Jonathan A Drezner
Journal: British Journal of Sports Medicine (2012)

Cardiovascular-related sudden death is the leading cause of mortality in athletes during sport.1 The majority of disorders associated with increased risk of sudden cardiac death (SCD), such as cardiomyopathies and primary electrical diseases, are suggested by abnormal findings present on an ECG. ECG interpretation in athletes requires careful analysis to properly distinguish physiological changes related to athlete's heart from findings suggestive of an underlying pathological cardiac condition. Whether used for the diagnostic evaluation of cardiovascular-related symptoms, a family history of inheritable cardiac disease or SCD, or for screening of asymptomatic athletes, ECG interpretation is an important skill for physicians involved in the cardiovascular care of athletes.

The purpose of this short report is to guide the clinician on the use of a two-page ECG criteria tool (Appendix, pages i7–i8 ). The science underpinning this instrument has been reported2 and demonstrates that providing standardised criteria to assist ECG interpretation in athletes significantly improves accuracy to distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience. The first page of the criteria tool consists of two tables. Table 1 lists each individual ECG criterion that should be considered abnormal, unrelated to athletic …
Evidence for Convergent Nucleotide Evolution and High Allelic Turnover Rates at the complementary sex determiner Gene of Western and Asian Honeybees
Authors: M. Hasselmann, X. Vekemans, J. Pflugfelder, N. Koeniger, G. Koeniger, S. Tingek, M. Beye
Journal: Molecular Biology and Evolution (2008)

Our understanding of the impact of recombination, mutation, genetic drift, and selection on the evolution of a single gene is still limited. Here we investigate the impact of all these evolutionary forces at the complementary sex determiner (csd) gene that evolves under a balancing mode of selection. Females are heterozygous at the csd gene and males are hemizygous; diploid males are lethal and occur when csd is homozygous. Rare alleles thus have a selective advantage, are seldom lost by the effect of genetic drift, and are maintained over extended periods of time when compared with neutral polymorphisms. Here, we report on the analysis of 17, 19, and 15 csd alleles of Apis cerana, Apis dorsata, and Apis mellifera honeybees, respectively. We observed great heterogeneity of synonymous (piS) and nonsynonymous (piN) polymorphisms across the gene, with a consistent peak in exons 6 and 7. We propose that exons 6 and 7 encode the potential specifying domain (csd-PSD) that has accumulated elevated nucleotide polymorphisms over time by balancing selection. We observed no direct evidence that balancing selection favors the accumulation of nonsynonymous changes at csd-PSD (piN/piS ratios are all <1, ranging from 0.6 to 0.95). We observed an excess of shared nonsynonymous changes, which suggest that strong evolutionary constraints are operating at csd-PSD resulting in the independent accumulation of the same nonsynonymous changes in different alleles across species (convergent evolution). Analysis of csd-PSD genealogy revealed relatively short average coalescence times ( approximately 6 Myr), low average synonymous nucleotide diversity (piS < 0.09), and a lack of trans-specific alleles that substantially contrasts with previously analyzed loci under strong balancing selection. We excluded the possibility of a burst of diversification after population bottlenecking and intragenic recombination as explanatory factors, leaving high turnover rates as the explanation for this observation. By comparing observed allele richness and average coalescence times with a simplified model of csd-coalescence, we found that small long-term population sizes (i.e., N(e) < 10(4)), but not high mutation rates, can explain short maintenance times, implicating a strong historical impact of genetic drift on the molecular evolution of highly social honeybees.
Acquired mutations in TET2 are common in myelodysplastic syndromes
Authors: Saskia M C Langemeijer, Roland P Kuiper, Marieke Berends, Ruth Knops, Mariam G Aslanyan, Marion Massop, Ellen Stevens-Linders, Patricia van Hoogen, Ad Geurts van Kessel, Reinier A P Raymakers, Eveline J Kamping, Gregor E Verhoef, Estelle Verburgh, Anne Hagemeijer, Peter Vandenberghe, Theo de Witte, Bert A van der Reijden, Joop H Jansen
Journal: Nature Genetics (2009)
Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan women but not men: results of a 2-year surveillance study
Authors: M.S. Ellabib, M. Agaj, Z. Khalifa, K. Kavanagh
Journal: British Journal of Dermatology (2002)

The reported frequency of recovery of fungi from infected nails varies according to the geographical area.To establish the nature of the causal agents in a sample of the Libyan population presenting with suspected onychomycosis.Samples were taken from the infected fingernails of 648 patients attending the Tripoli Medical Centre.Samples from 500 patients proved positive for fungi following culturing, while 476 were potassium hydroxide and culture positive. Of the culture-positive samples, yeasts of the genus Candida (C. albicans, C. parapsilosis, C. glabrata, C. guillermondii and C. tropicalis) were the dominant cause of this condition in women (417 of 434, 96%) but were responsible for only a minority of cases in men (three of 66, 5%). In contrast, dermatophytes (Trichophyton violaceum, T. rubrum, T. mentagrophytes and Microsporum canis) were responsible for this condition in the majority of cases in men (53 of 66, 80%) but only 3% (15 of 434) of cases in women. The mould Aspergillus nidulans was isolated from the nails of 10 (15%) men and two (0.5%) women.The data obtained in this study reveal an almost total separation of the aetiological agents responsible for onychomycosis based on gender.
ALUMINIUM SKELETON SPLINTS IN THE TREATMENT OF COMPOUND FRACTURES
Authors: C. M. Page
Journal: BMJ (1915)

These cases are interesting from-the fact that cerebrospinal meningitis in ailults is at present more common in England than it generally is, but wlhether these cases in infants are infections is doubtful.It will be best, however, in the future to treat them as possibly infectious and isolate theni in a fever hospital.None of these patients lhad any nasal discharge, except two cases, in whomn it came on just before death. ALUMINIIJM SKELETON SPLINTS IN THETREATMENT OF COMPOUND FRACTURES.
Banned end of life pathway is still in use under another name, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2015)

Background/Aim: Bladder cancer with histological variant (HV) has different morphological features from usual urothelial carcinoma (UC). The aim of this study was to evaluate the oncological outcomes of HV in patients with bladder cancer. Patients and Methods: We retrospectively evaluated data from 102 patients with UC of the bladder treated with radical cystectomy between 1998 and 2017. Pathological findings including HV were assigned by one dedicated pathologist. Recurrence-free survival (RFS) and cancer-specific survival (CSS) and overall survival (OS) were estimated by Cox regression models. Results: In total, 26 patients (25.5%) had HV, and the most common variant was squamous differentiation, followed by glandular differentiation and a mixed variant consisted of squamous and glandular differentiation. The presence of HV was associated with RFS and CSS (p=0.018, p=0.036, respectively). Conclusion: HV has more aggressive tumor biological features compared to those with pure UC. The presence of HV was associated with poor survival.
Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3
Authors: Daniel C Kraushaar, Wenfei Jin, Alika Maunakea, Brian Abraham, Misook Ha, Keji Zhao
Journal: Genome biology (2013)

Nucleosomes are present throughout the genome and must be dynamically regulated to accommodate binding of transcription factors and RNA polymerase machineries by various mechanisms. Despite the development of protocols and techniques that have enabled us to map nucleosome occupancy genome-wide, the dynamic properties of nucleosomes remain poorly understood, particularly in mammalian cells. The histone variant H3.3 is incorporated into chromatin independently of DNA replication and requires displacement of existing nucleosomes for its deposition. Here, we measure H3.3 turnover at high resolution in the mammalian genome in order to present a genome-wide characterization of replication-independent H3.3-nucleosome dynamics.We developed a system to study the DNA replication-independent turnover of nucleosomes containing the histone variant H3.3 in mammalian cells. By measuring the genome-wide incorporation of H3.3 at different time points following epitope-tagged H3.3 expression, we find three categories of H3.3-nucleosome turnover in vivo: rapid turnover, intermediate turnover and, specifically at telomeres, slow turnover. Our data indicate that H3.3-containing nucleosomes at enhancers and promoters undergo rapid turnover that is associated with active histone modification marks including H3K4me1, H3K4me3, H3K9ac, H3K27ac and the histone variant H2A.Z. The rate of turnover is negatively correlated with H3K27me3 at regulatory regions and with H3K36me3 at gene bodies.We have established a reliable approach to measure turnover rates of H3.3-containing nucleosomes on a genome-wide level in mammalian cells. Our results suggest that distinct mechanisms control the dynamics of H3.3 incorporation at functionally different genomic regions.