tbuckley/cabot-search huggingface dataset:
An ethics safe harbor for international genomics research?
Authors: Edward S Dove, Bartha M Knoppers, Ma’n H Zawati
Journal: Genome Medicine (2013)

Abstract Background Genomics research is becoming increasingly globally connected and collaborative, contesting traditional ethical and legal boundaries between global and local research practice. As well, global data-driven genomics research holds great promise for health discoveries. Yet, paradoxically, current research ethics review systems around the world challenge potential improvements in human health from such research and thus undermine respect for research participants. Case reports illustrate that the current system is costly, fragmented, inefficient, inadequate, and inconsistent. There is an urgent need to improve the governance system of ethics review to enable secure and seamless genomic and clinical data sharing across jurisdictions. Discussion Building on the international privacy 'safe harbor’ model that was developed following the adoption of the European Privacy Directive, we propose an international infrastructure. The goal is to create a streamlined and harmonized ethics governance system for international, data-driven genomics research projects. The proposed 'Safe Harbor Framework for International Ethics Equivalency’ would consist in part of an agency supporting an International Federation for Ethics Review (IFER), formed by a voluntary agreement among countries, granting agencies, philanthropies, institutions, and healthcare, patient advocacy, and research organizations. IFER would be both a central ethics review body and also a forum for review and follow-up of policies concerning ethics norms for international genomics research projects. It would be built on five principle elements: (1) registration; (2) compliance review; (3) recognition; (4) monitoring and enforcement; and (5) public participation. Summary A Safe Harbor Framework for International Ethics Equivalency would create many benefits for researchers, countries, and the general public, and may eventually have application beyond genomics to other areas of biomedical research that increasingly engage in secondary use of data and present only negligible risks. Among the benefits, research participants and patients would have uniform adequate protection, while researchers would be ensured expert ethics review with a reduction in cost, time, administrative hassle, and redundant regulatory hurdles. Most importantly, society would enjoy the maximization of the potential benefits of genomics research.
Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA.
Authors: G S Gilkeson, P Ruiz, A M Pippen, A L Alexander, J B Lefkowith, D S Pisetsky
Journal: The Journal of Experimental Medicine (1996)

Preautoimmune New Zealand Black/White (NZB/NZW) mice immunized with Escherichia coli (EC) double standard (ds) DNA produce antibodies that bind mammalian dsDNA and display specificities similar to spontaneous lupus anti-DNA. Since calf thymus (CT) dsDNA fails to induce these antibodies, these results suggest a special potency of foreign DNA in inducing serological manifestations of lupus in a susceptible host. To assess the effects of DNA immunization on clinical manifestations in NZB/NZW mice, we measured renal disease and survival of mice immunized with either (a) EC dsDNA as complexes with methylated bovine serum albumin (mBSA) in adjuvant; (b) CT dsDNA with mBSA in adjuvant; (c)mBSA alone in adjuvant; or (d) unimmunized. After immunization with EC dsDNA, NZB/NZW mice developed significant levels of anti-dsDNA antibodies. Nevertheless, these mice had less proteinuria, nitrate/nitrite excretion, and glomerular pathology than mice immunized with either mBSA alone, CT dsDNA/mBSA complexes, or unimmunized mice. Survival of the EC dsDNA immunized mice was significantly increased compared with the other mice. Furthermore, immunization of mice after the onset of anti-DNA production and proteinuria stabilized nephritis and prolonged survival. The improvement in renal disease occurred despite the expression of autoantibodies that bound mammalian dsDNA as well as glomerular antigens. These results suggest that bacterial DNA has immunological properties that attenuate murine lupus despite the induction of pathogenic antibodies.
Mechanism of Impaired Myocardial Function During Progressive Coronary Stenosis in Conscious Pigs
Authors: You-Tang Shen, Stephen F. Vatner
Journal: Circulation Research (1995)

The major goal of this study was to determine whether impaired myocardial contractile function during the development of progressive coronary artery stenosis induced by ameroid constriction in conscious pigs reflected myocardial "hibernation" or "stunning." Minipigs were instrumented with a coronary ameroid constrictor and hydraulic occluder, regional wall thickness crystals, a left ventricular (LV) pressure gauge, and aortic and left atrial catheters. In the seven pigs in which it was measured, systolic wall thickening (WT) distal to the ameroid fell by a maximum of 56 +/- 6% at 20 +/- 3 days after ameroid implantation and then began to recover. At 1 day after ameroid implantation, brief complete coronary artery occlusion (CAO) resulted in wall thinning distal to the ameroid (-113 +/- 4%) and transmural decreases in myocardial blood flow in endocardial (from 0.82 +/- 0.08 to 0.02 +/- 0.01 mL/min per gram) and epicardial (from 0.73 +/- 0.13 to 0.03 +/- 0.02 mL/min per gram) layers. At 20 +/- 3 days, baseline myocardial blood flow was not altered either in endocardial (0.92 +/- 0.10 mL/min per gram) or epicardial (0.85 +/- 0.12 mL/min per gram) layers, whereas brief complete coronary artery occlusion still reduced WT (-83 +/- 12%) and myocardial blood flow in endocardial (to 0.21 +/- 0.03 mL/min per gram) and epicardial (to 0.43 +/- 0.12 mL/min per gram) layers, indicating that the coronary artery was not totally occluded. Pathology in four pigs demonstrated no gross necrotic myocardium shortly after this time point. Transient reductions in WT distal to the ameroid were observed during progressive coronary artery stenosis in response to spontaneous increases in activity. Beat-by-beat analysis of these episodes revealed that acute reductions in WT followed increases in LV dP/dt and heart rate and exhibited delayed recovery. These data suggest that the reduced function during ameroid-induced coronary stenosis reflected cumulative myocardial stunning rather than a primary deficit in coronary blood flow or "hibernating myocardium."
Novel and Conventional Biomarkers for Prediction of Incident Cardiovascular Events in the Community
Authors: Olle Melander, Christopher Newton-Cheh, Peter Almgren, Bo Hedblad, Göran Berglund, Gunnar Engström, Margaretha Persson, J. Gustav Smith, Martin Magnusson, Anders Christensson, Joachim Struck, Nils G. Morgenthaler, Andreas Bergmann, Michael J. Pencina, Thomas J. Wang
Journal: JAMA (2009)

Prior studies have demonstrated conflicting results regarding how much information novel biomarkers add to cardiovascular risk assessment.To evaluate the utility of contemporary biomarkers for predicting cardiovascular risk when added to conventional risk factors.Cohort study of 5067 participants (mean age, 58 years; 60% women) without cardiovascular disease from Malmö, Sweden, who attended a baseline examination between 1991 and 1994. Participants underwent measurement of C-reactive protein (CRP), cystatin C, lipoprotein-associated phospholipase 2, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (N-BNP) and underwent follow-up until 2006 using the Swedish national hospital discharge and cause-of-death registers and the Stroke in Malmö register for first cardiovascular events (myocardial infarction, stroke, coronary death).Incident cardiovascular and coronary events.During median follow-up of 12.8 years, there were 418 cardiovascular and 230 coronary events. Models with conventional risk factors had C statistics of 0.758 (95% confidence interval [CI], 0.734 to 0.781) and 0.760 (0.730 to 0.789) for cardiovascular and coronary events, respectively. Biomarkers retained in backward-elimination models were CRP and N-BNP for cardiovascular events and MR-proADM and N-BNP for coronary events, which increased the C statistic by 0.007 (P = .04) and 0.009 (P = .08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). Net reclassification improvement was nonsignificant for cardiovascular events (0.0%; 95% CI, -4.3% to 4.3%) and coronary events (4.7%; 95% CI, -0.76% to 10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%; 95% CI, 0.7% to 14.1%; P = .03; coronary events: 14.6%; 95% CI, 5.0% to 24.2%; P = .003). However, correct reclassification was almost entirely confined to down-classification of individuals without events rather than up-classification of those with events.Selected biomarkers may be used to predict future cardiovascular events, but the gains over conventional risk factors are minimal. Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.
S21 Objective and patient reported outcomes of long term management of patients with chronic thromboembolic pulmonary hypertension (CTEPH): a single centre experience
Authors: N. J. Doughty, J. Pepke-Zaba
Journal: Thorax (2011)

<h3>Objective</h3> To determine long-term objective and Patient Reported Outcomes at a single centre in patients with CTEPH (distal or residual post Pulmonary endarterectomy). <h3>Method</h3> A retrospective study of all incident patients with CTEPH (2000–2011). Data obtained from the service database—6-minute walk test (6MWT), CAMbridge Pulmonary Hypertension Outcome Review (CAMPHOR) symptom, activity and Quality of Life (QoL) scores, and NTproBNP. Results obtained at baseline (at the time of diagnosis, pre-commencement of first targeted therapy), 3 months, 1, 2, 3, and 4 years follow-up. Over this period were managed according to clinical need and NCG guidelines. N=124. Targeted therapy defined as Prostacyclin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. <h3>Results</h3> Changes at 1st and 2nd time points (median 3 months and 1 year) show statistically significant improvements in patient reported outcomes and objective measures. The NTproBNP improvement peaks at 3 years and begins to tail off at 4 years. The 6MWD improvement plateaus out between 2 and 3 years. The CAMPHOR symptom score shows significant improvement including year 3. The 4-year 6MWD does not achieve statistical significance compared to baseline. Further investigation revealed that between the third and fourth year 22 subject9s follow-up was not performed; 3 died, 1 transferred to another centre, 18 are awaiting their 4-year follow-up. <h3>Conclusion</h3> Objective and patient reported measures of change over time show improvements for CTEPH patients up to 3 years. After 3 years it becomes more difficult to determine a categorical change. More 6MW and CAMPHOR data for the 4 year time point is needed to determine if initial improvements are sustained after 3 years in this patient group, or if the improvement seen really has begun to tail off as the results here may suggest. The 4-year follow-up data for the remaining 18 patients will be available later this year.
Down-Regulated Expression of Cytokeratin 18 Promotes Progression of Human Breast Cancer
Authors: Ute Woelfle, Guido Sauter, Sonja Santjer, Ruud Brakenhoff, Klaus Pantel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Cytokeratins (CKs) have been recognized for &amp;gt;20 years as structural marker proteins specific for epithelial cells. Recent expression profiling analyses indicate, however, that CK down-regulation may occur in breast cancer. Experimental Design: Here we evaluated the expression pattern of CK18 by immunohistochemical analysis of primary breast carcinomas (n = 1458) spotted on a high-density tissue microarray. The findings were correlated to histopathological risk factors and clinical outcome. Results: Down-regulation of CK18 (as compared to normal breast tissue) was observed in 25.4% of the tumors with a lower rate in lobular carcinomas (17.0%) than in ductal carcinomas (25.4%) or other histological entities (32.5%). CK down-regulation was significantly correlated to advanced tumor stage and high grade but not to axillary lymph node status. Kaplan-Meier survival analysis revealed CK18 as a prognostic indicator of overall survival (P = 0.015) and cancer-specific survival (P = 0.005). Conclusions: Down-regulation of the luminal CK18 is not rare and a clinically relevant event in breast cancer. This finding has important implications for the use of CK18 as epithelial tumor marker. The correlations with clinical follow-up suggest that CK18 might suppress tumor pro-gression.
Case report. Electromyographic evaluation of a water skiing injury.
Authors: M. O'Brien, F. J. Bonner, J. F. Bonner
Journal: British Journal of Sports Medicine (1978)

An Electromyographic diagnosis of an injury to the distal portion of the right posterior and medial cords of the Brachial plexus in a 40 year old male due to a water skiing accident is described.
STUDIES OF IDIOTYPIC ANTIBODIES
Authors: L. Scott Rodkey
Journal: The Journal of Experimental Medicine (1974)

Rabbits were immunized with a hapten-protein conjugate and sera were collected for 189 days. The antihapten antibodies were purified by affinity chromatography, then the same animal that synthesized the antibody was reinjected with polymerized F(ab')(2) fragments of antihapten antibodies. Sera were collected after autoimmunization and tested by an indirect radioimmunoassay technique for reaction with [(125)I]F(ab')(2) fragments of the original antihapten antibody. Results showed that each individual responded to its own F(ab')(2) and the antisera were specific for antihapten antibodies of that individual. Quantitative allotype assays established the immunoglobulin nature of the labeled test antigen. Inhibition assays showed that the reaction was specifically inhibitable with hapten. The relationship of this system with other idiotypic systems and the possible autoimmune implications of autoantiidiotypic antibodies are discussed.
AN ANONYMOUS ONLINE SURVEY OF THE VIEWS AND ATTITUDES OF MEDICAL STUDENTS AND JUNIOR DOCTORS TOWARDS PHYSICAL ACTIVITY (PA) TEACHING AND PROMOTION
Authors: Sophie Bates, Courtney Kipps
Journal: British Journal of Sports Medicine (2013)

Background Physical inactivity is the fourth leading cause of mortality globally according to the WHO. Several recent studies have highlighted that physical activity (PA) is inadequately covered during UK medical school training. This study aims to investigate the frequency of PA questions and advice during routine consultations by medical students and junior doctors. Methods A link to an anonymous online survey was sent to 195 medical students and 68 junior doctors based at a hospital near London. Thirty-four of the fifty responders were medical students. Results Less than a quarter of respondents routinely asked about PA levels in the medical history. In contrast, more than 90 percent always asked about tobacco and alcohol. Fear of offending or alienating patients, lack of knowledge and lack of time were the three most common themes identified by responders when asked about the perceived barriers to giving PA advice. Almost half reported having no teaching on PA guidelines. None of the medical students or junior doctors were able to correctly identify the WHO top 4 global mortality risk factors. Discussion/Conclusions This study found that clinical medical students and recent graduates rarely include questions or advice about PA in routine medical consultations. Responders tended to under prioritise physical inactivity as a mortality risk factor, and this may reflect a lack of adequate teaching and emphasis on physical inactivity within medical schools. Fear of offending of alienating patients was the most frequently cited barrier to giving PA advice. This may be due to the inexperience of juniors, or view that labelling someone as physically inactive is stigmatising. This study reaffirms previous findings of low levels of teaching about PA in medical schools and identifies lack of knowledge as one of the prime reasons why PA is neglected in routine medical history taking. This calls for urgent action to include PA teaching as a priority in UK medical school teaching.
Dietary antioxidants and magnesium in type 1 brittle asthma: a case control study
Authors: J C Baker, W S Tunnicliffe, R C Duncanson, J G Ayres
Journal: Thorax (1999)

Type 1 brittle asthma is a rare form of asthma. Atopy, psychosocial factors and diet may contribute to this condition. As increased dietary magnesium has a beneficial effect on lung function and selenium, vitamins A, C and E have antioxidant properties, a study was undertaken to test the hypothesis that patients with brittle asthma have diets deficient in these nutrients compared with subjects with non-brittle asthma and healthy adults.A case control study of the dietary intakes of 20 subjects with brittle asthma, 20 with non-brittle asthma, and 20 healthy adults was performed using five day weighed dietary records. Intake of magnesium was the primary outcome measure with selenium and vitamins A, C and E as secondary outcomes. Serum levels were measured at the same time as the dietary assessment.Sixty subjects (27 men) of mean age 49.5 years were recruited and completed the study. Subjects with brittle asthma had statistically lower median dietary intakes of vitamins A and E than the other groups (vitamin A: brittle asthma 522.5 micrograms/day, non-brittle asthma 869.5 micrograms/day, healthy adults 806.5 micrograms/day; vitamin E: brittle asthma 4.3 mg/day, non-brittle asthma 4.6 mg/day, healthy adults 4.5 mg/day). Median dietary intakes for the other nutrients were not significantly different between groups. Serum levels were within normal ranges for each nutrient in all subjects. Intakes less than the reference nutrient intake (RNI) for magnesium and vitamins A and C, and less than the safe intake (SI) for vitamin E were more likely in patients with brittle asthma than in those with non-brittle asthma.Nutrient deficiency and reduced antioxidant activity may contribute to disease activity in type 1 brittle asthma, although a prospective study of replacement therapy will be needed to confirm this hypothesis.
Use of a Pressure-Cycled Respirator (Bird) in Respiratory Failure Due to Severe Obstructive Pulmonary Disease
Authors: MARGARET BILLINGHAM
Journal: Annals of Internal Medicine (1969)

A pressure-cycled intermittent positive pressure respirator (IPPB) (Bird, Mark 7) was used to treat 42 episodes of severe acute respiratory failure in 32 patients with chronic obstructive pulmonary disease. This apparatus was able to reduce carbon dioxide levels in all but one patient, the mean pressure of carbon dioxide (PCO2) values decreasing by 32.5 mm Hg from the pre-IPPB level of 80.8 mm Hg within 24 to 48 hr after institution of IPPB. The effectiveness of the therapy is shown by the fact that no patients died in the first 3 days, only 6 patients (14%) died within the first 2 weeks, 33 episodes ended with removal from the respirator, and 21 patients (50%) were ultimately discharged from the hospital. We conclude that pressure-cycled respirators can be as effective as any other type of respirator, including those that are volume-cycled, if they are properly used and the results monitored by frequent arterial blood gas and pH measurements. The importance of controlled oxygen flow, inspiratory flow regulation, and controlled expiratory flow is discussed.
Predictors of work disability during the first 3 years after diagnosis in a national rheumatoid arthritis inception cohort
Authors: Tor Olofsson, Ingemar F Petersson, Jonas K Eriksson, Martin Englund, Julia F Simard, Jan-Åke Nilsson, Pierre Geborek, Lennart T H Jacobsson, Johan Askling, Martin Neovius
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To identify predictors of sick leave and disability pension in patients with early rheumatoid arthritis (RA). <h3>Methods</h3> Individuals aged 19–59 years diagnosed with early RA (≤12 months symptom duration) were identified in the Swedish Rheumatology Quality Register (1999–2007; n=3029). We retrieved days of sick leave and disability pension from the Swedish Social Insurance Agency and baseline predictors of total work days lost during 3 years after RA diagnosis were investigated using linear regression. Due to effect modification by baseline work ability (defined as work days lost the month before diagnosis), analyses were stratified into three categories: full=0 work days lost the month before diagnosis; partial=1–29 work days lost; and none=30 work days lost. <h3>Results</h3> 71% of patients with full baseline work ability still had full work ability after 3 years compared with 36% (p&lt;0.001) and 18% (p&lt;0.001) of those with partial and no work ability at baseline, respectively. Elevated baseline levels of HAQ and DAS28, higher age, lower education level and unemployment were associated with more work days lost during 3 years in all strata of baseline work ability (all p&lt;0.05). In a separate analysis, more objective variables (ESR, CRP and swollen joints) were not. Generally, the largest regression coefficients were seen for patients with partial baseline work ability. <h3>Conclusions</h3> Work ability at RA diagnosis was the most important predictor of 3-year sick leave and disability pension. Taking this into account, HAQ, DAS28, age and education level were also significant predictors, whereas ESR and CRP were not.
The Rabbit Placenta as an Organ of Diffusional Exchange
Authors: J. JOB FABER, FREDERICK M. HART
Journal: Circulation Research (1966)

The umbilical arteries of intact, in-situ placentas of one series of anesthetized rabbits were perfused with deoxygenated blood equilibrated with 10% or 20% acetylene and in another series with oxygenated blood without acetylene. The transfer of acetylene, and probably also of oxygen, were shown not to be limited by diffusion. Above the normal physiological rates of fetal placental flow, oxygen uptake in the fetal placental circulation did not increase appreciably with an increase in the rates of perfusion; below it, it decreased almost proportionally with a decrease in the rate of perfusion. To explore the applicability of these results to the human placenta, the experimental data were reduced to dimensionless form. It was shown that three dimensionless variables suffice to describe the characteristics of diffusional exchange in the placenta. The dimensionless diagrams were very similar for the ideal countercurrent exchanger and for the rabbit placenta but these differed from diagrams made from data published on human, sheep, cow, and monkey placentas. The authors propose the dimensionless diagram as a concise description of the passive transfer characteristics of a placenta, at least until measurements of vascular geometry, regional permeabilities and flow patterns allow the calculation of mean diffusion gradients.