tbuckley/cabot-search huggingface dataset:
Birmingham COPD cohort: Comparison of characteristics of employed with non-employed patients
Authors: Kiran Kalirai, Peymane Adab, Rachel Jordan, David Fitzmaurice, Jon Ayres
Journal: European Respiratory Journal (2013)

Introduction   Among those with COPD, 40% are of working age, but employment and work productivity are low. Little is known about factors affecting work performance in the UK.   Aims and objectives   To describe factors associated with work performance in a primary care cohort of COPD patients.   Methods   Patients with COPD from primary care are being recruited into a three-year cohort study. In addition to clinical data, occupational history and work performance are assessed. Interim baseline data was used to compare characteristics of those in and out of employment.   Results   Of 605 patients recruited so far, 11% were in work. Compared to those not in work, these patients are significantly younger (mean age 59.2 vs 69.6) more likely to be male (71.2% vs 66.0%) and current smokers (46.4% vs 25.0%). Adjusted for age, sex and smoking status, they have fewer co-morbidities (66.7% vs 74.3%, p for trend  Data will be updated at time of conference.   Conclusions   There are important clinical differences between COPD patients in and out of work, providing information for potential interventions.
How do we account for the absence of “change deafness”?
Authors: Frédéric Isel
Journal: Behavioral and Brain Sciences (2001)

O'Regan &amp; Noë (O&amp;N) argue that there is no need of internal, more or less picture-like, representation of the visual world in the brain. They propose a new approach in which vision is a mode of exploration of the world that is mediated by knowledge of sensorimotor contingencies. Data obtained in “change blindness” experiments support this assumption.
Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Alogliptin in Patients With Type 2 Diabetes and Inadequate Glycemic Control
Authors: Ralph A. DeFronzo, Penny R. Fleck, Craig A. Wilson, Qais Mekki
Journal: Diabetes Care (2008)

OBJECTIVE—To evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin in drug-naïve patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS—This double-blind, placebo-controlled, multicenter study included 329 patients with poorly controlled diabetes randomized to once-daily treatment with 12.5 mg alogliptin (n = 133), 25 mg alogliptin (n = 131), or placebo (n = 65) for 26 weeks. Primary efficacy end point was mean change from baseline in A1C at the final visit. RESULTS—At week 26, mean change in A1C was significantly greater (P &amp;lt; 0.001) for 12.5 mg (−0.56%) and 25 mg (−0.59%) alogliptin than placebo (−0.02%). Reductions in fasting plasma glucose were also greater (P &amp;lt; 0.001) in alogliptin-treated patients than in those receiving placebo. Overall, incidences of adverse events (67.4–70.3%) and hypoglycemia (1.5–3.0%) were similar across treatment groups. CONCLUSIONS—Alogliptin monotherapy was well tolerated and significantly improved glycemic control in patients with type 2 diabetes, without raising the incidence of hypoglycemia.
Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial
Authors: Jonathan Green, Tony Charman, Andrew Pickles, Ming W Wan, Mayada Elsabbagh, Vicky Slonims, Carol Taylor, Janet McNally, Rhonda Booth, Teodora Gliga, Emily J H Jones, Clare Harrop, Rachael Bedford, Mark H Johnson
Journal: The Lancet Psychiatry (2015)

Risk markers for later autism identified in the first year of life present plausible intervention targets during early development. We aimed to assess the effect of a parent-mediated intervention for infants at high risk of autism on these markers. We did a two-site, two-arm assessor-blinded randomised controlled trial of families with an infant at familial high risk of autism aged 7–10 months, testing the adapted Video Interaction to Promote Positive Parenting (iBASIS-VIPP) versus no intervention. Families were randomly assigned to intervention or no intervention groups using a permuted block approach stratified by centre. Assessors, but not families or therapists, were masked to group assignment. The primary outcome was infant attentiveness to parent. Regression analysis was done on an intention-to-treat basis. This trial is registered with ISCRTN Registry, number ISRCTN87373263. We randomly assigned 54 families between April 11, 2011, and Dec 4, 2012 (28 to intervention, 26 to no intervention). Although CIs sometimes include the null, point estimates suggest that the intervention increased the primary outcome of infant attentiveness to parent (effect size 0·29, 95% CI −0·26 to 0·86, thus including possibilities ranging from a small negative treatment effect to a strongly positive treatment effect). For secondary outcomes, the intervention reduced autism-risk behaviours (0·50, CI −0·15 to 1·08), increased parental non-directiveness (0·81, 0·28 to 1·52), improved attention disengagement (0·48, −0·01 to 1·02), and improved parent-rated infant adaptive function (χ2[2] 15·39, p=0·0005). There was a possibility of nil or negative effect in language and responsivity to vowel change (P1: ES–0·62, CI −2·42 to 0·31; P2: −0·29, −1·55 to 0·71). With the exception of the response to vowel change, our study showed positive estimates across a wide range of behavioural and brain function risk-markers and developmental outcomes that are consistent with a moderate intervention effect to reduce the risk for later autism. However, the estimates have wide CIs that include possible nil or small negative effects. The results are encouraging for development and prevention science, but need larger-scale replication to improve precision. Autistica, Waterloo Foundation, Autism Speaks, and the UK Medical Research Council.
Determining the Relationship Between Toxicity and Quality of Life in an Ovarian Cancer Chemotherapy Clinical Trial
Authors: Lorna Butler, Monica Bacon, Mark Carey, Benny Zee, Dongsheng Tu, Andrea Bezjak
Journal: Journal of Clinical Oncology (2004)

This analysis of data from a randomized trial of chemotherapy in epithelial ovarian cancer sought to determine whether a relationship exists between the presence and severity of the most commonly observed toxic effects and the corresponding quality of life (QOL) items.One hundred fifty-two eligible patients accrued from Canada by the National Cancer Institute of Canada Clinical Trials Group on a randomized trial of paclitaxel and cisplatin versus cyclophosphamide/cisplatin were included in the analysis. Toxicity to the chemotherapeutic treatments was subjectively evaluated using a trial-specific checklist for ovarian cancer and the European Organization for Research and Treatment of Cancer QLQ C30+3 questionnaire. Assessments were conducted at baseline, before each cycle of treatment (3 weeks), and at each 3-month follow-up during the next 2 years (or until progression).The most frequently observed symptoms experienced during or shortly following chemotherapy were neurosensory loss, lethargy, nausea, vomiting, and alopecia. Regression analyses revealed that change scores of QOL items related to motor weakness and gastrointestinal pain were common predictors for the change global QOL score during protocol treatment; and change scores of QOL items related to lethargy or fatigue and change toxicity grade of mood predicted the change global QOL score after patients were off treatment.The use of the European Organization for Research and Treatment of Cancer QLQ C30+3 and trial-specific checklist was able to assess the effect of expected toxicities on patient' s QOL during and following treatment, and so may be useful in addressing the concerns regarding methodological issues that have limited the acquisition of prospective, longitudinal treatment-related toxicity data.
The FIFA/F-MARC update on doping
Authors: J Dvorak, P McCrory, M D’Hooghe, M Saugy
Journal: British Journal of Sports Medicine (2006)

The ongoing media debate surrounding the issue of doping in sport has raised public awareness of a problem that been steadily developing over many years. This controversy reflects both the rapid development of various sports disciplines as well as the evolution of new doping methods and agents.

The Federation Internationale de Football Association (FIFA) introduced doping controls in football in 1970 to ensure that the results of national and international matches were a fair reflection of the ability of those taking part. Over the past 12 years, the FIFA Medical Assessment and Research Centre (F-MARC) has developed a worldwide network of specialists who are involved in the educational process within the regional football confederations and national associations as one facet of global anti-doping strategies. F-MARC has also been involved in the practical implementation of doping controls for FIFA competitions at all levels. FIFA has developed close collaboration …
Affective Responsiveness in Borderline Personality Disorder: A Psychophysiological Approach
Authors: S C Herpertz, H J Kunert, U B Schwenger, H Sass
Journal: American Journal of Psychiatry (1999)

The aim of the study was to investigate affective responses to emotional stimuli in subjects with borderline personality disorder.Twenty-four female patients with borderline personality disorder and 27 normal female comparison subjects were examined. The test stimuli were a set of standardized photographic slides with pleasant, neutral, or unpleasant emotional valence. In addition to self-reports, emotional reactions to the slides were measured by heart rate, skin conductance, and startle response. Psychometric tests for various aspects of impulsiveness were also completed.Neither self-report nor physiological data gave any evidence that the borderline patients showed more intense affective responses than did the normal subjects. The borderline subjects did not produce higher levels of startle amplitude, and while viewing unpleasant slides, they showed a startle potentiation effect that was largely similar to that of the comparison group. In fact, the borderline patients showed low electrodermal responses to all three stimulus categories, which points to physiological underarousal.The results do not agree with the hypothesis that there is a fundamental, biologically based affective hyperresponsiveness in borderline personality disorder, as is suggested by current theories of affect dysregulation in the disorder. Autonomic underarousal may seriously interfere with a flexible adaptation to environmental stimuli.
Membrane Receptor for Thyroid Hormone: Physiologic and Pharmacologic Implications
Authors: Paul J. Davis, Faith B. Davis, Shaker A. Mousa, Mary K. Luidens, Hung-Yun Lin
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Plasma membrane integrin αvβ3 is a cell surface receptor for thyroid hormone at which nongenomic actions are initiated. L-thyroxine (T₄) and 3,3',5-triiodo-L-thyronine (T₃) promote angiogenesis and tumor cell proliferation via the receptor. Tetraiodothyroacetic acid (tetrac), a deaminated T₄ derivative, blocks the nongenomic proliferative and proangiogenic actions of T₄ and T₃. Acting at the integrin independently of T₄ and T₃, tetrac and a novel nanoparticulate formulation of tetrac that acts exclusively at the cell surface have oncologically desirable antiproliferative actions on multiple tumor cell survival pathway genes. These agents also block the angiogenic activity of vascular growth factors. Volume and vascular support of xenografts of human pancreatic, kidney, lung, and breast cancers are downregulated by tetrac formulations. The integrin αvβ3 receptor site for thyroid hormone selectively regulates signal transduction pathways and distinguishes between unmodified tetrac and the nanoparticulate formulation. The receptor also mediates nongenomic thyroid hormone effects on plasma membrane ion transporters and on intracellular protein trafficking.
Placebo-Controlled Evaluation of Four Novel Compounds for the Treatment of Schizophrenia and Schizoaffective Disorder
Authors: Herbert Y. Meltzer, Lisa Arvanitis, Deborah Bauer, Werner Rein
Journal: American Journal of Psychiatry (2004)

Four studies using identical protocols evaluated the safety and efficacy of four novel, evidence-based targets for antipsychotic agents: a neurokinin (NK(3)) antagonist (SR142801), a serotonin 2A/2C (5-HT(2A/2C)) antagonist (SR46349B), a central cannabinoid (CB(1)) antagonist (SR141716), and a neurotensin (NTS(1)) antagonist (SR48692).Adults with schizophrenia or schizoaffective disorder (N=481) were randomly assigned in a 3:1:1 ratio to receive fixed doses of investigational drug, placebo, or haloperidol for 6 weeks. Primary efficacy variables included changes from baseline in total score on the Positive and Negative Syndrome Scale, severity of illness score on the Clinical Global Impression (CGI), and total score and psychosis cluster score on the Brief Psychiatric Rating Scale (BPRS).Significantly greater improvement in all primary efficacy variables was seen in the group receiving haloperidol than in the group receiving placebo at 6 weeks (endpoint analyses), indicating the validity of the study. The group receiving the NK(3) antagonist showed significantly greater improvement over baseline than the group receiving placebo as measured by Positive and Negative Syndrome Scale total score, CGI severity of illness score, and BPRS psychosis cluster score. Reductions in the Positive and Negative Syndrome Scale total and negative scores in the group receiving the 5-HT(2A/2C) antagonist were significantly larger than those in the group receiving placebo. The improvements in psychopathology produced by the NK(3) and 5-HT(2A/2C) antagonists were smaller than those produced by haloperidol, although the response to the NK(3) antagonist was positively correlated with plasma levels. The groups receiving the CB(1) and NTS(1) antagonists did not differ from the group receiving placebo on any outcome measure. All investigational drugs were well tolerated.The novel design used in this study permitted the use of a smaller number of patients receiving placebo to test the efficacy of the four novel compounds. The NK(3) and 5-HT(2A/2C) antagonists showed evidence of efficacy in the treatment of schizophrenia and schizoaffective disorder. Study limitations preclude a definitive conclusion on the efficacy of CB(1) and NTS(1) antagonists in the treatment of schizophrenia. Further study of these two promising nondopaminergic mechanisms to treat schizophrenia and schizoaffective disorder appears indicated.
Type I collagen formation in rat type II alveolar cells immortalised by viral gene products.
Authors: R Matsui, R H Goldstein, K Mihal, J S Brody, M P Steele, A Fine
Journal: Thorax (1994)

BACKGROUND--Alveolar type II (T2) cells synthesise matrix proteins such as type IV collagen and fibronectin. In contrast, a fetal rat T2 cell line has been shown to synthesise type I and III collagen as well as type IV collagen. To study regulation of collagen production in T2 cells, neonatal T2 cells immortalised by adenoviral 12SE1A gene transfer were used. It was previously reported that this immortalised cell line (E1A-T2) retains epithelial features such as tight junctions and cytokeratins but also expresses mesenchymal features such as vimentin. METHODS--Collagen production was examined in E1A-T2 and primary neonatal T2 cells using polyacrylamide gel electrophoresis. Electron microscopy was used to examine collagen deposition in E1A-T2 cell culture. To define the mechanism by which alpha 1(I) type I collagen gene expression was activated in E1A-T2 cells, a deletional analysis of alpha 1(I) promoter constructs linked to the bacterial chloramphenicol acetyltransferase gene was performed. RESULTS--E1A-T2 cells produced large amounts of type I collagen with a predominance of alpha 1(I) homotrimers; alpha 2(I) peptides were detected only in the cell layer. In contrast, primary neonatal rat T2 cell cultures produced a trace amount of type I collagen. Production of alpha 1(I) peptide chains (per microgram DNA) in E1A-T2 cell cultures was 30 times higher than that observed in primary neonatal T2 cell cultures. Electron microscopy showed deposition of type I collagen fibrils in the extracellular matrix of E1A-T2 cell cultures. Transfection studies suggested at least two cis-acting elements which mediate increased alpha 1(I) gene expression in E1A-T2 cells. CONCLUSIONS--These studies indicate that the E1A-T2 cell line may be useful for studying type I collagen gene regulation in alveolar T2 cells. These findings also raise the possibility that viral activation of type I collagen genes in alveolar epithelium may be involved in certain forms of pulmonary fibrosis.
Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas
Authors: Kathryn P. Pennington, Tom Walsh, Maria I. Harrell, Ming K. Lee, Christopher C. Pennil, Mara H. Rendi, Anne Thornton, Barbara M. Norquist, Silvia Casadei, Alexander S. Nord, Kathy J. Agnew, Colin C. Pritchard, Sheena Scroggins, Rochelle L. Garcia, Mary-Claire King, Elizabeth M. Swisher
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain. Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway. Results: Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation. Conclusions: Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials. Clin Cancer Res; 20(3); 764–75. ©2013 AACR.
STUDIES IN EXPERIMENTAL SYPHILIS
Authors: Alan M. Chesney, Jarold E. Kemp
Journal: The Journal of Experimental Medicine (1925)

1. The size of the dose of the infecting material exerts an appreciable effect upon the duration of the incubation period in experimental syphilis of the rabbit. Other things being equal, the larger the dose the shorter is the incubation period. 2. The size of the inoculum was not found to exercise any marked effect upon the course of the disease as a whole. 3. In individual rabbits inoculated with minimal amounts of virus the disease may run a malignant course.
Assessment of Recent HIV-1 Infection by a Line Immunoassay for HIV-1/2 Confirmation
Authors: Jörg Schüpbach, Martin D Gebhardt, Zuzana Tomasik, Christoph Niederhauser, Sabine Yerly, Philippe Bürgisser, Lukas Matter, Meri Gorgievski, Rolf Dubs, Detlev Schultze, Ingrid Steffen, Corinne Andreutti, Gladys Martinetti, Bruno Güntert, Roger Staub, Synove Daneel, Pietro Vernazza
Journal: PLoS Medicine (2007)

Background Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay. Methods and Findings The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (≤ 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%–46%). Conclusions Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.
Hypoxic ventilatory response in successful extreme altitude climbers
Authors: L. Bernardi, A. Schneider, L. Pomidori, E. Paolucci, A. Cogo
Journal: European Respiratory Journal (2005)

A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on. To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured. Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers. Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.