tbuckley/cabot-search huggingface dataset:
Small increase in GP trainee numbers is “vote of confidence,” says RCGP
Authors: Abi Rimmer
Journal: BMJ (2016)

Figures released by Health Education England showing that GP trainee numbers have increased by 1 percentage point are a “vote of confidence” in the profession, the chair of the Royal College of General Practitioners has said.

Figures released on Thursday 31 March detailing the acceptance and fill rates into specialty training programmes showed that 70% (2296) of GP training posts had been filled after the first round of recruitment …
Osteoglycin attenuates cardiac fibrosis by suppressing cardiac myofibroblast proliferation and migration through antagonizing lysophosphatidic acid 3/matrix metalloproteinase 2/epidermal growth factor receptor signalling
Authors: Caojian Zuo, Xiaodong Li, Jun Huang, Dongrui Chen, Kaida Ji, Yan Yang, Tingyan Xu, Dingliang Zhu, Chen Yan, Pingjin Gao
Journal: Cardiovascular Research (2018)

Cardiac myofibroblasts (CMFs) play a crucial role in the progression of pathological fibrotic cardiac remodelling. The expression of osteoglycin (OGN) is increased in diseased hearts; however, the role of OGN in pathological cardiac remodelling is not understood. Here, we sought to determine the effect of OGN on cardiac interstitial fibrosis and investigate the molecular mechanisms of OGN in CMF activation and matrix production. We found that OGN expression was significantly upregulated in mouse hearts in response to chronic 14-day angiotensin II (Ang II) infusion. Mice lacking OGN (OGN−/−) exhibited enhanced cardiac interstitial fibrosis and significantly more severe cardiac dysfunction following Ang II infusion compared to wild-type mice. OGN deficiency did not alter blood pressure, nor had effect on transforming growth factor-beta signalling activation, but presented with increased proliferative activity in hearts. In vitro studies with isolated CMFs revealed that OGN deficiency significantly increased proliferation and migration and enhanced the transactivation of epidermal growth factor receptor (EGFR) signalling by Ang II. On the other hand, OGN overexpression in CMFs decreased their proliferation and migration via reducing EGFR activation. Overexpression of OGN also suppressed the shedding of membrane anchored EGFR ligand. Moreover, OGN was found to interact with a lysophosphatidic acid (LPA) receptor isoform 3 and thus to attenuate EGFR transactivation through blocking cell surface translocation of membrane type 1 matrix metalloproteinase (MT1-MMP) and subsequent pro-MMP-2 activation in a Ras homolog gene family, member A (RhoA)/Rho-associated, coiled-coil containing protein kinase (ROCK)-dependent manner. These findings suggest that OGN negatively regulates cardiac fibrotic remodelling by attenuating CMF proliferation and migration through LPA3-mediated and Rho/ROCK-dependent inhibition of MT1-MMP translocation, MMP2 activation and EGFR transactivation.
Postgraduate leadership development: a cross specialty trainees’ perspective
Authors: Alex Till, Archana Anandaram, Andrew Dapaah, Ramez Ibrahim, Akshay Kansagra, Radhika Prasad, Ian Randall, Clara Serrecchia, Philippa Thomas, Rachel Trickey, Judy McKimm
Journal: BMJ (2016)

Alex Till and colleagues consider the development of leadership skills in basic specialty training
Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension
Authors: Kurt R Stenmark, Maria G Frid, Brian B Graham, Rubin M Tuder
Journal: Cardiovascular Research (2018)

Pulmonary hypertension (PH) is the end result of interaction between pulmonary vascular tone and a complex series of cellular and molecular events termed 'vascular remodelling'. The remodelling process, which can involve the entirety of pulmonary arterial vasculature, almost universally involves medial thickening, driven by increased numbers and hypertrophy of its principal cellular constituent, smooth muscle cells (SMCs). It is noted, however that SMCs comprise heterogeneous populations of cells, which can exhibit markedly different proliferative, inflammatory, and extracellular matrix production changes during remodelling. We further consider that these functional changes in SMCs of different phenotype and their role in PH are dynamic and may undergo significant changes over time (which we will refer to as cellular plasticity); no single property can account for the complexity of the contribution of SMC to pulmonary vascular remodelling. Thus, the approaches used to pharmacologically manipulate PH by targeting the SMC phenotype(s) must take into account processes that underlie dominant phenotypes that drive the disease. We present evidence for time- and location-specific changes in SMC proliferation in various animal models of PH; we highlight the transient nature (rather than continuous) of SMC proliferation, emphasizing that the heterogenic SMC populations that reside in different locations along the pulmonary vascular tree exhibit distinct responses to the stresses associated with the development of PH. We also consider that cells that have often been termed 'SMCs' may arise from many origins, including endothelial cells, fibroblasts and resident or circulating progenitors, and thus may contribute via distinct signalling pathways to the remodelling process. Ultimately, PH is characterized by long-lived, apoptosis-resistant SMC. In line with this key pathogenic characteristic, we address the acquisition of a pro-inflammatory phenotype by SMC that is essential to the development of PH. We present evidence that metabolic alterations akin to those observed in cancer cells (cytoplasmic and mitochondrial) directly contribute to the phenotype of the SM and SM-like cells involved in PH. Finally, we raise the possibility that SMCs transition from a proliferative to a senescent, pro-inflammatory and metabolically active phenotype over time.
THE PROGNOSTIC VALUE OF LEFT ATRIAL FUNCTION BY SPECKLE TRACKING STRAIN IMAGING IN PATIENTS WITH PERIPARTUM CARDIOMYOPATHY
Authors: Yuko Soyama, Dennis McNamara, Masataka Sugahara, Joan Briller, Leslie Cooper, Julie Damp, Mark Drazner, James Fett, Eileen Hsich, Navin Rajagopalan, Nobuyuki Kagiyama, John Gorcsan
Journal: Journal of the American College of Cardiology (2018)
Getting through without charging through
Authors: Suki S Sandhu
Journal: BMJ (2005)

We investigated radiation exposure of patients undergoing whole-body <sup>18</sup>F-FDG PET/CT examinations at 4 hospitals equipped with different tomographs. <b>Methods:</b> Patient doses were estimated by using established dose coefficients for <sup>18</sup>F-FDG and from thermoluminescent measurements performed on an anthropomorphic whole-body phantom. <b>Results:</b> The most relevant difference between the protocols examined was the incorporation of CT as part of the combined PET/CT examination: Separate low-dose CT scans were acquired at 2 hospitals for attenuation correction of emission data in addition to a contrast-enhanced CT scan for diagnostic evaluation, whereas, at the other sites, contrast-enhanced CT scans were used for both purposes. Nevertheless, the effective dose per PET/CT examination was similar, about 25 mSv. <b>Conclusion:</b> The dosimetric concepts presented in this study provide a valuable tool for the optimization of whole-body <sup>18</sup>F-FDG PET/CT protocols. Further reduction of patient exposure can be achieved by modifications to the existing hardware and software of PET/CT systems.
Prediction of psychosis across protocols and risk cohorts using automated language analysis
Authors: Cheryl M. Corcoran, Facundo Carrillo, Diego Fernández‐Slezak, Gillinder Bedi, Casimir Klim, Daniel C. Javitt, Carrie E. Bearden, Guillermo A. Cecchi
Journal: World Psychiatry (2018)

Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer-based natural language processing analyses, we previously showed that, among English-speaking clinical (e.g., ultra) high-risk youths, baseline reduction in semantic coherence (the flow of meaning in speech) and in syntactic complexity could predict subsequent psychosis onset with high accuracy. Herein, we aimed to cross-validate these automated linguistic analytic methods in a second larger risk cohort, also English-speaking, and to discriminate speech in psychosis from normal speech. We identified an automated machine-learning speech classifier - comprising decreased semantic coherence, greater variance in that coherence, and reduced usage of possessive pronouns - that had an 83% accuracy in predicting psychosis onset (intra-protocol), a cross-validated accuracy of 79% of psychosis onset prediction in the original risk cohort (cross-protocol), and a 72% accuracy in discriminating the speech of recent-onset psychosis patients from that of healthy individuals. The classifier was highly correlated with previously identified manual linguistic predictors. Our findings support the utility and validity of automated natural language processing methods to characterize disturbances in semantics and syntax across stages of psychotic disorder. The next steps will be to apply these methods in larger risk cohorts to further test reproducibility, also in languages other than English, and identify sources of variability. This technology has the potential to improve prediction of psychosis outcome among at-risk youths and identify linguistic targets for remediation and preventive intervention. More broadly, automated linguistic analysis can be a powerful tool for diagnosis and treatment across neuropsychiatry.
BMA Wales rejects proposals for 2013-14 GP contract
Authors: Helen Jaques
Journal: BMJ (2013)

Proposed changes to the general medical services (GMS) contract for 2013-14 have been rejected by the BMA in Wales because of its concern over plans to phase out the minimum practice income guarantee.

The BMA’s Welsh General Practitioners Committee said that up to half of general practices in Wales could be “fatally” destabilised by the plan to cease use of a correction factor to guarantee a minimum level of funding for practices. The committee said that an agreement on the contract with the Welsh government …
Sex differences and factors influencing the duration of the QT interval in patients on anti-tuberculosis therapy
Authors: Gerardo Alvarez-Uria, Manoranjan Midde
Journal: European Respiratory Journal (2018)

In an ECG, the QT interval represents the depolarisation and repolarisation of the ventricles and is usually corrected for heart rate (QTc). Previous studies have shown that women have a reduced repolarisation reserve and greater susceptibility to the QTc prolongation effect of some drugs [1, 2]. Sex has a strong influence on the QTc prolongation effect of first-line TB drugs and gatifloxacin <http://ow.ly/UXtP30hJJCu> Data used in the preparation of this article were obtained from the Platform for Aggregations of Clinical TB Studies (codr.c-path.org). The Platform for Aggregations of Clinical TB Studies initiative is a public–private partnership launched in May 2015 by Critical Path Institute (C-Path), the Special Programme for Research and Training in Tropical Diseases (TDR), the Global Alliance for TB Drug Development (TB Alliance), and St. George's University of London.
GALECTIN-3 INDEPENDENTLY PREDICTS THE RISK OF EARLY MORTALITY AFTER SUDDEN CARDIAC ARREST
Authors: Wassim Mosleh, Zaid Al-Jebaje, Sahoor Khan, Milind Chaudhari, Tanvi Shah, Charl Khalil, Kevin Frodey, Suraj Dahal, Umesh Sharma
Journal: Journal of the American College of Cardiology (2018)
P018 Protease activated receptor 2 (PAR2) expression in the myeloid compartment impacts osteoclastogenesis
Authors: S McGrath, L Hultin, JC Lockhart, CS Goodyear
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Protease activated receptor 2 (PAR2) is a G protein coupled receptor responsive to serine proteases, which plays a key role in inflammation and pain reception. Rheumatoid arthritis (RA) patients have up-regulated surface expression of PAR2 in circulating monocytes which correlates with disease activity. We have previously demonstrated that <i>Par2</i><sup>-/-</sup> mice are protected from inflammation, bone erosion, and cartilage destruction in a Freund's Complete Adjuvant (FCA) induced arthritis model. However, it is unclear how PAR2 affects the composition of the myeloid compartment and osteoclastogenesis. <h3>Objectives</h3> The aim of this study was to evaluate the impact of loss of PAR2 on the myeloid compartment and osteoclastogenesis. <h3>Methods</h3> Bone marrow (BM) from 6–10 week old <i>Par2</i><sup>-/-</sup> and control C57BL/6 mice was cultured in pro-osteoclastogenic media for 5 days and the generated mature osteoclasts, tartrate-resistant acid phosphatase positive (TRAP) multinucleated cells, were counted. The resorption potential of these cells was assessed using osteolysis plates and the total osteo-resorption quantified after 7–14 days of culture. BM was also collected for flow cytometric analysis of the haematopoietic cellular composition (with the following markers: CD3, B220, CD11b, Ly6C, Ly6G, CD115, and CD117) and assessed for osteoclast precursors. <h3>Results</h3> <i>In vitro</i> osteoclastogenesis revealed an increase in numbers of mature osteoclasts from <i>Par2</i><sup>-/-</sup> BM compared to WT, corresponding with increased levels of resorption. Flow cytometry of BM from both WT and <i>Par2</i><sup>-/-</sup> mice showed 3 distinct monocyte populations defined by the cell surface expression levels of CD11b and Ly6C. The overall ratio of these populations was not altered in <i>Par2</i><sup>-/-</sup> animals. <h3>Conclusions</h3> BM from <i>Par2</i><sup>-/-</sup> mice has increased osteoclastogenic potential and overall resorptive activity. We propose that this is not due to differences in bone marrow residing osteoclast pre-cursor numbers. This study indicates a potential role for PAR2 in osteoclast differentiation and bone remodelling. <h3>Acknowledgements</h3> The research was funded by Medical Research Scotland (MRS) and supported by Astrazeneca. <h3>Disclosure of interest</h3> S. McGrath: None declared, L. Hultin Employee of: Astrazeneca, J. Lockhart: None declared, C. Goodyear Consultant for: AstraZeneca
Death, eaters, and dark marks
Authors: Matthew Collin
Journal: The Journal of Experimental Medicine (2018)

The maintenance of macrophage populations, role of environmental cues in shaping their physiology, and the response of resident cells to perturbation are critical factors in tissue homeostasis with implications for many pathological scenarios. Pigment-containing cells of the dermis are the latest to come under the scrutiny of a mouse-induced depletion model.
Hospital Readmission After Perioperative Acute Myocardial Infarction Associated With Noncardiac Surgery
Authors: Nathaniel R. Smilowitz, Joshua A. Beckman, Scott E. Sherman, Jeffrey S. Berger
Journal: Circulation (2018)

Acute myocardial infarction (AMI) is a major cardiovascular complication of noncardiac surgery. We aimed to evaluate the frequency, causes, and outcomes of 30-day hospital readmission after perioperative AMI.
“KEEPING THEM AWAKE DOES IT MATTER?” PREDICTORS OF PROLONGED LENGTH OF STAY FOLLOWING TRANSCUTANEOUS AORTIC VALVE REPLACEMENT
Authors: Upamanyu Rampal, Rahul Vasudev, Hiten Patel, Salvatore M. Zisa, Habib Habib, Namrata Paul, Hartaj Virk, Mahesh Bikkina, Fayez Shamoon
Journal: Journal of the American College of Cardiology (2018)
Seroprevalence of Coxiella burnetii antibodies and chronic Q fever among post-mortal and living donors of tissues and cells from 2010 to 2015 in the Netherlands
Authors: Sonja E van Roeden, Eleonoor W Holsboer, Jan Jelrik Oosterheert, Jorge P van Kats, Jacqueline van Beckhoven, Boris M Hogema, Marja J van Wijk
Journal: Eurosurveillance (2018)

BackgroundAfter a large Q fever outbreak in the Netherlands in the period from 2007 to 2010, the risk of Q fever transmission through tissue and cell transplantation from undiagnosed chronic Q fever cases became a potential issue. Aim: We aimed to evaluate the risk of Q fever transmission through tissue and cell transplantation. Methods: We performed a retrospective observational cohort study among 15,133 Dutch donors of tissues and stem cells from 2010 to 2015 to assess seroprevalence of Coxiella burnetii antibodies, to identify factors associated with presence of C. burnetii antibodies, and to assess the proportion of undiagnosed chronic Q fever cases. Results: The study population consisted of 9,478 (63%) femoral head donors, 5,090 (34%) post-mortal tissue donors and 565 (4%) cord blood donors. Seroprevalence of C. burnetii antibodies gradually decreased after the outbreak, from 2.1% in 2010 to 1.4% in 2015, with a significant trend in time (p < 0.001). Of 301 seropositive donors, seven (2.3%) were newly detected with chronic Q fever (0.05% of all screened donors). Conclusion: This study shows that seroprevalence of C. burnetii antibodies among donors of tissues and cells in the Netherlands after 2014 was similar to pre-outbreak levels in the general population. The proportion of newly detected chronic Q fever patients among donors of tissues and cells was smaller than 0.1%. This study may prompt discussion on when to terminate the screening programme for chronic Q fever in donors of tissues and cells in the Netherlands.
Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials
Authors: Federico Coccolini, Matteo Nardi, Giulia Montori, Marco Ceresoli, Andrea Celotti, Stefano Cascinu, Paola Fugazzola, Matteo Tomasoni, Olivier Glehen, Fausto Catena, Yutaka Yonemura, Luca Ansaloni
Journal: International Journal of Surgery (2018)
Carving event and episodic memory at their joints
Authors: Nazim Keven
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra (M&amp;C) argue that event and episodic memories share the same scenario construction process. I think this way of carving up the distinction throws the baby out with the bathwater. If there is a substantive difference between event and episodic memory, it is based on a difference in the construction process and how they are organized, respectively.
Doctors with non-NHS incomes risk breaching pension tax allowances when auto-enrolment begins, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors in the NHS pension scheme who earn private or non-pensionable NHS income could breach their pension tax allowance if they are auto-enrolled in a workplace pension scheme, the BMA has warned.

John Canning, chairman of the BMA’s professional fees committee, also said that GP practices needed to be ready to automatically enrol their staff into a workplace pension scheme. In October 2012 the roll-out of workplace pensions through “auto-enrolment” began. The largest employers were the first who were required to automatically enrol staff earning over £9440 a year into a workplace pension scheme. …
Applicability of Publicly Reported Hospital Readmission Measures to Unreported Conditions and Other Patient Populations
Authors: Neel M. Butala, Daniel B. Kramer, Changyu Shen, Jordan B. Strom, Kevin F. Kennedy, Yun Wang, Linda R. Valsdottir, Jason H. Wasfy, Robert W. Yeh
Journal: Annals of Internal Medicine (2018)

Readmission rates after hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among Medicare beneficiaries are used to assess quality and determine reimbursement. Whether these measures reflect readmission rates for other conditions or insurance groups is unknown.To investigate whether hospital-level 30-day readmission measures for publicly reported conditions (HF, AMI, and pneumonia) among Medicare patients reflect those for Medicare patients hospitalized for unreported conditions or non-Medicare patients hospitalized with HF, AMI, or pneumonia.Cross-sectional.Population-based.Hospitals in the all-payer Nationwide Readmissions Database in 2013 and 2014.Hospital-level 30-day all-cause risk-standardized excess readmission ratios (ERRs) were compared for 3 groups of patients: Medicare beneficiaries admitted for HF, AMI, or pneumonia (Medicare reported group); Medicare beneficiaries admitted for other conditions (Medicare unreported group); and non-Medicare beneficiaries admitted for HF, AMI, or pneumonia (non-Medicare group).Within-hospital differences in ERRs varied widely among groups. Medicare reported ratios differed from Medicare unreported ratios by more than 0.1 for 29% of hospitals and from non-Medicare ratios by more than 0.1 for 46% of hospitals. Among hospitals with higher readmission ratios, ERRs for the Medicare reported group tended to overestimate ERRs for the non-Medicare group but underestimate those for the Medicare unreported group.Medicare groups and risk adjustment differed slightly from those used by the Centers for Medicare & Medicaid Services.Hospital ERRs, as estimated by Medicare to determine financial penalties, have poor agreement with corresponding measures for populations and conditions not tied to financial penalties. Current publicly reported measures may not be good surrogates for overall hospital quality related to 30-day readmissions.Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.
Patterns of response to androgen deprivation therapy in younger patients with locally advanced or metastatic prostate cancer.
Authors: Matthew Keating, Lisa Giscombe, Andre Desouza, Shiva Kumar Reddy Mukkamalla, Ritesh Rathore
Journal: Journal of Clinical Oncology (2018)

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).