tbuckley/cabot-search huggingface dataset:
The attributable mortality of delirium in critically ill patients: prospective cohort study
Authors: P. M. C. Klein Klouwenberg, I. J. Zaal, C. Spitoni, D. S. Y. Ong, A. W. van der Kooi, M. J. M. Bonten, A. J. C. Slooter, O. L. Cremer
Journal: BMJ (2014)

<b>Objective</b> To determine the attributable mortality caused by delirium in critically ill patients. <b>Design</b> Prospective cohort study. <b>Setting</b> 32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013. <b>Participants</b> 1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours. <b>Exposures</b> Trained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium. <b>Main outcome measure</b> Mortality during admission to an intensive care unit. <b>Results</b> Among 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P&lt;0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval −7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval −0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76). <b>Conclusions</b> Overall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality. <b>Trial registration</b> Clinicaltrials.gov NCT01905033.
Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis
Authors: Antonella Pellicoro, Rebecca L. Aucott, Prakash Ramachandran, Andrew J. Robson, Jonathan A. Fallowfield, Victoria K. Snowdon, Stephen N. Hartland, Madeleine Vernon, Jeremy S. Duffield, Christopher R. Benyon, Stuart J. Forbes, John P. Iredale
Journal: Hepatology (2011)

Elastin has been linked to maturity of liver fibrosis. To date, the regulation of elastin secretion and its degradation in liver fibrosis has not been characterized. The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP-12) in its turnover during fibrosis. Liver fibrosis was induced by either intraperitoneal injections of carbon tetrachloride (CCl(4) ) for up to 12 weeks (rat and mouse) or oral administration of thioacetamide (TAA) for 1 year (mouse). Elastin synthesis, deposition, and degradation were investigated by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blotting, and casein zymography. The regulation of MMP-12 elastin degradation was defined mechanistically using CD11b-DTR and MMP-12 knockout mice. In a CCl(4) model of fibrosis in rat, elastin deposition was significantly increased only in advanced fibrosis. Tropoelastin expression increased with duration of injury. MMP-12 protein levels were only modestly changed and in coimmunoprecipitation experiments MMP-12 was bound in greater quantities to its inhibitor TIMP-1 in advanced versus early fibrosis. Immunohistochemistry and macrophage depletion experiments indicated that macrophages were the sole source of MMP-12. Exposure of CCl(4) in MMP-12(-/-) mice led to a similar degree of overall fibrosis compared to wildtype (WT) but increased perisinusoidal elastin. Conversely, oral administration of TAA caused both higher elastin accumulation and higher fibrosis in MMP-12(-/-) mice compared with WT.Elastin is regulated at the level of degradation during liver fibrosis. Macrophage-derived MMP-12 regulates elastin degradation even in progressive experimental liver fibrosis. These observations have important implications for the design of antifibrotic therapies.
US court says employers can deny contraceptive coverage for religious reasons
Authors: M. McCarthy
Journal: BMJ (2014)

In a five to four decision, the US Supreme Court has ruled that the federal government cannot force closely held companies to cover contraceptives if the owners have religious objections.1 2 The decision was written by Justice Samuel Alito.

Under the 2010 Affordable Care Act all health insurance plans were required to cover essential preventive services without any cost sharing requirements.

Based on the advice of the Institute of Medicine, the Obama administration ruled this requirement should include coverage for all 20 contraceptive products approved by the US Food and Drug Administration.

The Obama administration argued that since unintended pregnancies can have …
Intercalated degrees, learning styles, and career preferences: prospective longitudinal study of UK medical students
Authors: I C McManus, P Richards, B C Winder
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To assess the effects of taking an intercalated degree (BSc) on the study habits and learning styles of medical students and on their interest in a career in medical research <b>Design:</b> Longitudinal questionnaire study of medical students at application to medical school and in their final year. <b>Setting:</b> All UK medical schools <b>Participants:</b> 6901 medical school applicants for admission in 1991 were studied in the autumn of 1990. 3333 entered medical school in 1991 or 1992 and 2695 who were due to qualify in 1996 or 1997 were studied 3 months before the end of their clinical course. Response rates were 92% for applicants and 56% for final year students. <b>Main outcome measures:</b> Study habits (surface, deep, and strategic learning style) and interest in different medical careers, including medical research. Identical questions were used at time of application and in final year. <b>Results:</b> Students who had taken an intercalated degree had higher deep and strategic learning scores than at application to medical school Those with highest degree classes had higher strategic and deep learning scores and lower surface learning scores. Students taking intercalated degrees showed greater interest in careers in medical research and laboratory medicine and less interest in general practice than their peers. The effects of the course on interest in medical research and learning styles were independent. The effect of the intercalated degree was greatest in schools where relatively few students took intercalated degrees. <b>Conclusions:</b> Intercalated degrees result in a greater interest in research careers and higher deep and strategic learning scores. However, the effects are much reduced in schools where most students intercalate a degree Introduction of intercalated degrees for all medical students without sufficient resources may not therefore achieve its expected effects. <h3>Key messages</h3> Although intercalated degrees are well established, little is known about their effect on medical students In this longitudinal study final year students who had taken intercalated degree were more interested in medical research, and had higher deep and strategic learning style scores than other students The effects of the intercalated degree were dose dependent, being greatest in those gaining a first class degree The effects of the intercalated degree were greatest in medical schools where a relatively small proportion of medical students took the degree Differences between medical schools are most easily explained by resource dilution
Dealing with uncertainties: ethics of prenatal diagnosis and preimplantation genetic diagnosis to prevent mitochondrial disorders
Authors: A.L. Bredenoord, G. Pennings, H.J. Smeets, G. de Wert
Journal: Human Reproduction Update (2007)

This paper aims to address the ethical issues regarding prenatal diagnosis and preimplantation genetic diagnosis (PGD) of mitochondrial disorders. Owing to the absence of effective treatment, the prevention of the transmission of mitochondrial disorders is considered to be of key importance. The characteristics of mtDNA, such as heteroplasmy and the genetic bottleneck, make it difficult to estimate recurrence risks correctly and to provide an accurate prognosis for many mtDNA mutations. A limited number of mtDNA mutations allow reliable predictions, though results in the 'grey zone' are problematic. Both prenatal diagnosis and PGD for mtDNA disorders are complicated by the interpretation of the test results. As a consequence, these applications confront both clinical practice and society at large with several ethical questions and issues for further debate, among which the acceptability of suboptimal genetic testing, the value and research use of embryos, the evaluation of late abortion, the ethics of PGD for disorders with an incomplete penetrance and variable expression, the possible transfer of embryos with residual health risks, the acceptability of risks and drawbacks of genetic reproductive technology in general, and the scope and limits of reproductive autonomy and professional responsibility.
Dynamic Regulation of Myelination in Health and Disease
Authors: Patrick Long, Gabriel Corfas
Journal: JAMA Psychiatry (2014)

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Screening for interstitial lung disease in systemic sclerosis: performance of high-resolution CT with limited number of slices: a prospective study
Authors: Thomas Frauenfelder, Anna Winklehner, Thi Dan Linh Nguyen, Rucsandra Dobrota, Stephan Baumueller, Britta Maurer, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Early diagnosis of interstitial lung disease (ILD), currently the main cause of death in systemic sclerosis (SSc), is needed. The gold standard is high-resolution CT (HRCT) of the chest, but regular screening faces the risk of increased radiation exposure. We performed a prospective validation of a dedicated, 9-slice HRCT protocol with reduced radiation dose for the detection of ILD in patients with SSc. <h3>Methods</h3> We analysed 170/205 consecutive patients with SSc. Whole-chest HRCT, serving as standard of reference, and the reduced HRCT with nine slices allocated according to a basal–apical gradient were obtained. ILD presence, extent (&gt; or &lt;20%) and diagnostic confidence were assessed. The reduced HRCT was independently analysed by two blinded radiologists, who also evaluated image quality. Radiation dose parameters were calculated. <h3>Results</h3> Standard chest HRCT showed ILD in 77/170 patients. With the reduced HRCT, 68/77 cases with ILD were identified (sensitivity 88.3%, both readers). The accuracy (91.8%, reader 1; 94.7%, reader 2), diagnostic confidence (98.8%, reader 1; 95.3%, reader 2) and image quality rates were high. Minimal ILD was correctly quantified in 73.1% (reader 1)/71.2% (reader 2) and extensive ILD in 88% (reader 1)/100% (reader 2). Importantly, the reduced HRCT had a significantly lower radiation dose. The mean dose length product (effective dose) was only 5.66±4.46 mGycm (0.08±0.06 mSv) compared with the standard protocol dose of 149.00±95.90 mGycm (2.09±1.34 mSv). <h3>Conclusions</h3> The above-described reduced chest HRCT protocol reliably detects even mild SSc-ILD in clinical practice, with the advantage of a much lower radiation dose compared with standard whole-chest HRCT.
Safety, Pharmacokinetics, and Pharmacodynamics of AMG 102, a Fully Human Hepatocyte Growth Factor–Neutralizing Monoclonal Antibody, in a First-in-Human Study of Patients with Advanced Solid Tumors
Authors: Michael S. Gordon, Christopher J. Sweeney, David S. Mendelson, S. Gail Eckhardt, Abraham Anderson, Darrin M. Beaupre, Daniel Branstetter, Teresa L. Burgess, Angela Coxon, Hongjie Deng, Paula Kaplan-Lefko, Ian M. Leitch, Kelly S. Oliner, Lucy Yan, Min Zhu, Lia Gore
Journal: Clinical Cancer Research (2010)

The aims were to assess the safety, pharmacokinetics, maximum tolerated dose, and antitumor activity of AMG 102, a fully human hepatocyte growth factor/scatter factor (HGF/SF)-neutralizing monoclonal antibody, in patients with solid tumors.Patients (N = 40) with refractory advanced solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 mg/kg AMG 102 every 2 weeks). Safety, anti-AMG 102 antibody formation, pharmacokinetics, tumor response, and exploratory biomarkers were assessed.AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, and the maximum tolerated dose was not reached. Treatment-related adverse events were generally mild and included fatigue (13%), constipation (8%), nausea (8%), vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced grade 3 upper gastrointestinal hemorrhage. No anti-AMG 102 antibodies were detected, and AMG 102 had linear pharmacokinetics within the dose range investigated. Sixteen of 23 (70%) evaluable patients had a best response of stable disease with progression-free survival ranging from 7.9 to 40 weeks. Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a dose-dependent manner, whereas soluble c-Met concentrations were generally similar across doses.AMG 102 is safe and well tolerated, has a favorable pharmacokinetic profile, and will be further investigated as a monotherapy and in combination with other agents.
Altered Golgi apparatus in hydrostatically loaded articular cartilage chondrocytes.
Authors: J J Parkkinen, M J Lammi, A Pelttari, H J Helminen, M Tammi, I Virtanen
Journal: Annals of the Rheumatic Diseases (1993)

Articular cartilage proteoglycan content is controlled by joint loading. This study aimed to elucidate the role of hydrostatic pressure in this regulation.Primary cultures of chondrocytes from bovine articular cartilage, grown on coverslips, were subjected to 5, 15, or 30 MPa hydrostatic pressure, applied continuously or cyclically at 0.125 or 0.05 Hz. The Golgi apparatus was visualised either by a fluorochrome coupled wheat germ agglutinin or by transmission electron microscopy. Proteoglycan synthesis was studied by the incorporation of sulphur-35 labelled sulphate.After 30 MPa continuous hydrostatic pressure, the Golgi apparatus was observed in a compact form with a concomitant decrease in proteoglycan synthesis. The normal stacked appearance of the Golgi apparatus was no more visible in the electron microscopy preparation of the pressurised chondrocytes. This effect was reversible and was also noticed after 15 MPa continuous load, though to a minor extent. Cyclic pressures (5-30 MPa) caused no apparent change in the Golgi apparatus. The shape of some cells changed to a more retracted form after 30 MPa continuous pressure. Nocodazole, which causes disassembly of the microtubules, blocked the compacting influence of pressurisation on the Golgi apparatus, and reduced proteoglycan synthesis to about half of the control level.The packing of the Golgi apparatus is dependent on microtubules and may contribute to the inhibition of proteoglycan synthesis observed in articular cartilage subjected to high hydrostatic pressure.
Electrophysiological effects of a new class III antiarrhythmic agent (E-4031) on the conduction and refractoriness of the in vivo human atrium
Authors: A. Shimizu, M. Fukatani, A. Konoe, S. Isomoto, O. A Centurion, K. Yano
Journal: Cardiovascular Research (1993)

Objective: The aim was to test the efficacy of a new class III drug, E-4031, on human atrial muscle in vivo. Methods: Electrophysiological measurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 μg·kg−1·min−1) which followed an initial dose of 9 μg·kg−1·5 min−1. Extrastimuli at 500 ms were delivered from the right atrial appendage, high lateral right atrium, and low lateral right atrium. The effective refractory period, repetitive atrial firing zone, and fragmented atrial activity zone were assessed at three sites in the right atrium. The conduction delay zone from the stimulus artefact to the distal electrode pair at the coronary sinus was also measured. Results: E-4031 caused a significant increase in overall right atrial effective refractory period from 210(SD 29) to 232(26) ms (p<0.001, n=30 sites). There were significant decreases in the incidence of repetitive atrial firing (67% to 37%: p<0.005), in the repetitive atrial firing zone [23(20) to 11(22) ms: p<0.01], and in the fragmented atrial activity zone [15(22) to 3(8) ms: p<0.005], but no significant change in the conduction delay zone. However, E-4031 significantly prolonged the longest coupling interval that elicited conduction delay, from 249(31) ms to 267(28) ms (p<0.01). E-4031 had no effect on the conduction time except at coupling intervals close to the atrial effective refractory period. Conclusion: These results suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.
Feasibility and Safety of Pulmonary Vein Isolation Using a New Mapping and Navigation System in Patients With Refractory Atrial Fibrillation
Authors: Thomas Arentz, Jörg von Rosenthal, Thomas Blum, Jochem Stockinger, Gerd Bürkle, Reinhold Weber, Nikolaus Jander, Franz Josef Neumann, Dietrich Kalusche
Journal: Circulation (2003)

Ostial pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation can cure patients with atrial fibrillation (AF); however, this procedure carries the risk of PV stenosis. The aim of this study was to assess the feasibility of a new mapping and navigation technique using a multipolar basket catheter (BC) for PV isolation in patients with refractory AF and to analyze its safety with regard to PV stenosis at long-term follow-up.We studied 55 patients (mean age, 53+/-11 years; 40 male) with drug-refractory AF (paroxysmal, n=37; persistent, n=18). A 64-pole BC was placed transseptally into each of the accessible PVs. By use of a nonfluoroscopic navigation system, the ablation catheter was guided to the BC electrodes at the PV ostium, with earliest activation during sinus rhythm. RF was delivered by use of maximum settings of temperature at 50 degrees C and power at 30 W. The end point of the procedure was the complete elimination of all distal and fragmented ostial PV potentials. Of 165 targeted veins, 163 were successfully isolated with a mean RF duration of 720+/-301 seconds per vein. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs. Contrast-enhanced magnetic resonance angiography revealed 2 PV stenoses of >25% out of 165 treated vessels.The use of a multipolar BC allowed effective and safe PV isolation by combining 3D mapping and navigation. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs, and the incidence of relevant diameter reduction of the treated PVs was 1.2%.
The effect of air filtration on airborne dog allergen
Authors: R Green, A Simpson, A Custovic, B Faragher, M Chapman, A Woodcock
Journal: Allergy (1999)

Background: Effective methods of reducing dog allergen are required to help alleviate symptoms in asthmatic patients sensitized to dog who refuse to part with their pet. The aim of this study was to investigate the use of the high efficiency particulate air (HEPA) filter air cleaner to reduce airborne Can f 1 in homes with a dog. Methods: The effect of a HEPA air cleaner was investigated in nine homes with a dog. Samples were collected from two rooms of each house concurrently, one of which contained the dog, on two separate days (active day – HEPA air cleaner on – and control day). Eight consecutive 1‐h samples were collected from each room with a high‐volume air sampler (airflow rate 60 l/min). Can f 1 was determined by monoclonal‐polyclonal antibody‐based ELISA. Results: Baseline airborne Can f 1 levels were 3.8‐fold greater when sampling was performed with a dog in the room (GM 27.1 ng Can f 1/m 3 , range 2.63–329) than when the dog was elsewhere in the house (GM 7.1 ng Can f 1/m 3 , range 0.69–27.2). When the dog was elsewhere in the house, airborne Can f 1 levels fell on both active and control days, but the magnitude of the reduction was significantly greater on the active days ( P &lt;0.05), and was approximately 90% from baseline. With the dog in the room, a significant fall in airborne Can f 1 was observed only on active days (75% from baseline), but not on control days (active vs control P &lt;0.001). Conclusions: HEPA air cleaners reduce airborne Can f 1 in homes with dogs. Furthermore, preventing the access of the dog to the bedroom and possibly the living room may reduce the total allergen load inhaled.
Examination of the relationship between variation at 17q21 and childhood wheeze phenotypes
Authors: Raquel Granell, A. John Henderson, Nicholas Timpson, Beate St. Pourcain, John P. Kemp, Susan M. Ring, Karen Ho, Stephen B. Montgomery, Emmanouil T. Dermitzakis, David M. Evans, Jonathan A.C. Sterne
Journal: Journal of Allergy and Clinical Immunology (2012)
Intra-articular pressure in rheumatoid arthritis of the knee. 3. Pressure changes during joint use.
Authors: M I Jayson, A S Dixon
Journal: Annals of the Rheumatic Diseases (1970)

Passive knee flexionThe subject was encouraged to relax completely.The lower leg was firmly grasped by an observer and the knee was lifted and the heel firmly flexed up to the thigh.With progressive distension this movement produced symptoms of extreme joint tightness and tension and the maximum degree of flexion was progressively