tbuckley/cabot-search huggingface dataset:
Working of a Hearing-aid Clinic
Authors: R. S. Stevenson
Journal: BMJ (1948)

The earliest hearing-aid was probably the hand held behind the ear, and ear trumpets and tubes go back at least 250 years.Non-electric aids, such as ear trumpets and auricles, magnify only to a slight extent-about 15 decibels-but this can be surprisingly helpful, especially to an elderly deaf person afraid of the mechanics of an electric aid.The first electric hearing-aid, which was in essentials a portable telephone, was made in 1898 in America by the Dictagraph Company; this was a micro-telephone type of aid which worked from a single low-tension battery and generally had a carbon granule microphone with a hard or soft carbon dia- phragm.The micro-telephone apparatus was quite convenient to carry about, but amplification was confined to the lower notes, and so it was useful only to cases of conductive(" middle-ear ") deafness and not to cases of perceptive (" nerve") deafness.In
Injury incidence in qualification runs versus final runs in FIS World Cup snowboard cross and ski cross
Authors: Sophie E Steenstrup, Tone Bere, Tonje W Flørenes, Roald Bahr, Lars Nordsletten
Journal: British Journal of Sports Medicine (2011)

Background In the International Ski Federation (FIS), World Cup (WC) snowboard cross (SBX) and ski cross (SX), the injury incidence in individual qualification runs versus final runs in heats of four athletes is unknown. Objective To investigate the injury incidence in individual qualification runs versus final runs of SBX and SX. Methods Injuries were recorded by the FIS injury surveillance system (FIS ISS) through retrospective athlete interviews at the end of each season during four WC seasons (2006–2010). A total of 713 athletes (345 SBX and 368 SX) were interviewed. Time-loss injuries occurring during SBX and SX competitions were included. Injury incidence was expressed as the relative injury rate (per 1000 runs). Results For SBX, the injury incidence per 1000 runs in finals was 12.1 vs 6.1 in qualifications (RR 1.9, 95% CI 1.1–3.5). The injury incidence was 12.9 in finals and 4.4 in qualifications (RR 2.9, 95% CI 1.4–6.2) for SBX males and 10.5 vs 9.3 (RR 1.1, 95% CI 0.5–2.8) for females. For SX, the injury incidence in finals was 12.4 and 9.2 in qualifications (RR 1.4, 95% CI 0.8–2.3). The injury incidence for SX males was 13.6 in finals vs 8.8 in qualifications (RR 1.5, 95% CI 0.8–3.1) and10.8 vs 9.8 (RR 1.1, 95% CI 0.5–2.6) for females. Conclusion The injury incidence was significantly higher in final runs compared with qualification runs in SBX for males. For SBX females and in SX, no significant differences were found.
S81 Refractory asthma in the UK: a follow-up analysis
Authors: J. Sweeney, C. E. Brightling, A. Menzies-Gow, R. M. Niven, L. G. Heaney
Journal: Thorax (2011)

<h3>Introduction</h3> Refractory asthma poses a major healthcare problem with limited therapies currently available and new therapies needed. The British Thoracic Society (BTS) Difficult Asthma Network has previously published demographic data on a cohort of patients with well-characterised refractory asthma1 using a National Registry and detailed follow-up data is now available. <h3>Methods</h3> Data on 349 of the original 382 patients was available from 4 specialist centres across the UK–Royal Brompton Hospital, London, Glenfield Hospital, Leicester, University Hospital of South Manchester and Belfast City Hospital. Data have been used to examine healthcare utilisation, therapeutic strategies and lung function compared to baseline. <h3>Results</h3> The median follow-up period was 3.1 years (IQR 1.9–5.5 years). Improvements from baseline were noted in Pre bronchodilator FEV<sub>1</sub>% predicted (66%±23.6% vs 72.7%±26.8%; p&lt;0.001) and Pre bronchodilator FVC% predicted (82.7%±20.3% vs 86.5%±21.5%; p&lt;0.01). Reduced rescue steroids (Median 2{IQR 4–6} vs 0 {IQR 2–4}; p&lt;0.001), a reduction in hospital admissions (Median 0 {IQR 0–2} vs 0 {IQR 0–1}; p&lt;0.01) and reduced unscheduled visits to GP9s or A&amp;E (Median 4 {IQR 2–6} vs 2 {IQR 0–6}; p&lt;0.05) was seen. The most frequent therapeutic intervention was the introduction of maintenance oral steroids (OCS): 42% of the original cohort was on maintenance OCS at baseline, with 58% on maintenance OCS at follow-up. Most on OCS at baseline remained on OCS but 30 (9%) discontinued and 78 (22%) had OCS initiated. Steroid sparing agents (methotrexate, cyclosporine, azathioprine etc) were tried but showed minimal steroid sparing benefit with a success rate of between 0.6 and 3.2%. Omalizumab was only suitable for trial in 59 (17%) subjects with a response rate of 66%. In those who had a successful Omalizamub trial, 23 (92%; p&lt;0.001) were successful in achieving either a reduction in OCS or complete withdrawal. <h3>Conclusion</h3> In specialist centres, healthcare outcomes and lung function are improved in patients with refractory asthma. The most frequent intervention is the progression to maintenance OCS and treatment options remain limited. Steroid sparing agents show little benefit with the exception of Omalizamub.
The impact of low-dose busulfan on clonal dynamics in nonhuman primates
Authors: Ken Kuramoto, Dean Follman, Peiman Hematti, Stephanie Sellers, Mikko O. Laukkanen, Ruth Seggewiss, Mark E. Metzger, Allen Krouse, Robert E. Donahue, Christof von Kalle, Cynthia E. Dunbar
Journal: Blood (2004)
Role of p90 Ribosomal S6 Kinase–Mediated Prorenin-Converting Enzyme in Ischemic and Diabetic Myocardium
Authors: Seigo Itoh, Bo Ding, Tetsuro Shishido, Nicole Lerner-Marmarosh, Nadan Wang, Naoya Maekawa, Bradford C. Berk, Yasuchika Takeishi, Chen Yan, Burns C. Blaxall, Jun-ichi Abe
Journal: Circulation (2006)

Background— Epidemiological data strongly indicate that diabetes increases the incidence of heart failure. Although the benefit of angiotensin-converting enzyme inhibitor (ACE-I) treatment during and after myocardial infarction has been found to be greater in diabetics than nondiabetics and activation of the renin-angiotensin system (RAS) has been implicated, the molecular basis of these actions remains unclear. Methods and Results— We generated transgenic mice with cardiac-specific overexpression of wild-type p90 ribosomal S6 kinase (WT-p90RSK-Tg) and a dominant-negative form of p90RSK (DN-p90RSK-Tg). Recovery of cardiac function after ischemia/reperfusion in WT-p90RSK-Tg isolated mouse hearts was significantly impaired. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed specific induction of prorenin-converting enzyme (PRECE) in WT-p90RSK-Tg mice. mRNA induction of PRECE was confirmed with serial angiotensinogen protein reduction after perfusion in WT-p90RSK-Tg mice, suggesting an increase of angiotensinogen cleavage and subsequent RAS activation in WT-p90RSK-Tg mice. We investigated the role of the RAS in WT-p90RSK-Tg animals after ischemia/reperfusion with the use of an ACE-I (captopril) and an angiotensin II type 1 receptor blocker (olmesartan). We did not observe any effect of these inhibitors in non-Tg littermate controls, thus corroborating other reports in rodents. In contrast, both captopril and olmesartan significantly improved cardiac function and reduced infarct size in WT-p90RSK-Tg mice. At 8 months of age, WT-p90RSK-Tg mice developed cardiac dysfunction. p90RSK activity and PRECE mRNA were both increased by streptozotocin-induced hyperglycemia in non-Tg littermate controls, whereas DN-p90RSK-Tg animals exposed to streptozotocin did not have PRECE induction. Conclusions— This study demonstrates the critical role of p90RSK in hyperglycemia-mediated myocardial PRECE induction, which may explain the augmentation of the RAS in diabetic hearts and provide an alternative therapeutic approach to treat diabetic cardiomyopathy.
Chemo-Immunotherapy of Metastatic Colorectal Carcinoma With Gemcitabine Plus FOLFOX 4 Followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Induces Strong Immunologic and Antitumor Activity in Metastatic Colon Cancer Patients
Authors: Pierpaolo Correale, Maria Grazia Cusi, Kwong Yok Tsang, Maria Teresa Del Vecchio, Stefania Marsili, Marco La Placa, Chiara Intrivici, Angelo Aquino, Lucia Micheli, Cristina Nencini, Francesco Ferrari, Giorgio Giorgi, Enzo Bonmassar, Guido Francini
Journal: Journal of Clinical Oncology (2005)

Tumor cell killing by anticancer drugs may be supported by their immuno- and pharmacologic effects. Chemotherapy is in fact able to (A) upregulate tumor-associated antigen expression, including carcinoembryonic antigen (CEA) or other target molecules such as thymidylate synthase (TS); and (B) downregulate tumor cell resistance to the death signals induced by tumor antigen-specific cytotoxic T lymphocytes. This provides the rationale for combining chemo- and immunotherapy.We describe the results of a translational phase II trial designed to evaluate the toxicity, antitumor activity and immunologic effects of gemcitabine + FOLFOX-4 (oxaliplatin, fluorouracil, and folinic acid) polychemotherapy followed by the subcutaneous administration of granulocyte macrophage colony-stimulating factor and low-dose interleukin-2 in colorectal carcinoma patients. The study involved 29 patients (16 males and 13 females with a mean age of 69 years), 21 of whom had received a previous line of treatment, and 19 had liver involvement.The treatment was well tolerated and induced very high objective response (68.9%) and disease control rates (96.5%), with an average time to progression of 12.5 months. An immunologic study of peripheral blood mononuclear cells (PBMCs) taken from 20 patients showed an enhanced proliferative response to colon carcinoma antigen and a significant reduction in suppressive regulatory T lymphocytes (CD4+CD25T-reg+). A cytofluorimetric study of the PBMCs of five HLA-A(*)02.01+ patients who achieved an objective response showed an increased frequency of cytolytic T lymphocyte precursors specific for known CEA- and TS-derived epitopes.The results show that our regimen has strong immunologic and antitumor activity in colorectal cancer patients and deserves to be investigated in phase III trials.
Predicting an accelerated lung function decline in smokers: is there a proper threshold?
Authors: Reinier P. Akkermans, Marion Biermans, Bas Robberts, Gerben ter Riet, Annelies Jacobs, Chris van Weel, Michel Wensing, Tjard Schermer
Journal: European Respiratory Journal (2013)

From the authors: 

We thank F.A.A. Mohamed Hoesein and P. Zanen for their interest in our work [1]. In our study, we performed secondary analyses on data from the Lung Health Study (LHS) [2]. We subdivided the LHS study population into four categories based on the presence or absence of airflow obstruction as defined the fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70 cut-off point and by the lower fifth percentile using the LMS (lambda, mu, sigma) method definitions. The LMS method accounts for sex- and age-specific predicted values (mu), and adjusts for nonuniform dispersion (sigma) and skewness of the lung function values distribution (lambda). The original LHS study population consisted of 5887 smokers aged 35–60 years. We excluded 1842 subjects because 1276 subjects were in different categories based on the fixed and LMS definitions for airflow obstruction during their baseline and first annual visits, and 566 subjects …
Host Gene Regulation During Coxsackievirus B3 Infection in Mice
Authors: Lydia A. Taylor, Christopher M. Carthy, Decheng Yang, Kareem Saad, Donald Wong, George Schreiner, Lawrence W. Stanton, Bruce M. McManus
Journal: Circulation Research (2000)

Abstract —Host genetic responses that characterize enteroviral myocarditis have not yet been determined. The injurious and inflammatory process in heart muscle may reflect host responses of benefit to the virus and ultimately result in congestive heart failure and dilated cardiomyopathy. On the other hand, host responses within the myocardium may secure the host against acute or protracted damage. To investigate the nature of modified gene expression in comparison with normal tissue, mRNA species were assessed in myocardium using cDNA microarray technology at days 3, 9, and 30 after infection. Of 7000 clones initially screened, 169 known genes had a level of expression significantly different at 1 or more postinfection time points as compared with baseline. The known regulated genes were sorted according to their functional groups and normalized expression patterns and, subsequently, interpreted in the context of viremic, inflammatory, and healing phases of the myocarditic process.
Clinical Correlates and Consequences of Anemia in a Broad Spectrum of Patients With Heart Failure
Authors: Eileen O’Meara, Tim Clayton, Margaret B. McEntegart, John J.V. McMurray, Chim C. Lang, Simon D. Roger, James B. Young, Scott D. Solomon, Christopher B. Granger, Jan Östergren, Bertil Olofsson, Eric L. Michelson, Stuart Pocock, Salim Yusuf, Karl Swedberg, Marc A. Pfeffer
Journal: Circulation (2006)

Background— We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). Methods and Results— In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate &lt;60 mL · min −1 · 1.73 m −2 compared with &lt;30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P &lt;0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. Conclusions— Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.
X-Linked Lymphoproliferative Syndrome Registry
Authors: Janet K. Hamilton
Journal: JAMA (1979)

To the Editor.—  The X-Linked Lymphoproliferative Syndrome Registry was recently established and is funded by the National Cancer Institute. We invite referrals of possible cases of the X-linked lymphoproliferative syndrome as well as unusual complications associated with infectious mononucleosis. The following criteria may be used to ascertain whether a case is a candidate for the registry: (1) phenotypes ( N Engl J Med 297:1077-1081, 1977) of the proliferative types including fatal infectious mononucleosis, immunoblastic sarcoma of B cells, immunodeficiency with hyper-IgM following infectious mononucleosis, or American-Burkitt's lymphoma, aproliferative phenotypes such as agranulocytosis, aplastic anemia, or acquired agammaglobulinemia, (2) the phenotypes of X-linked lymphoproliferative syndrome in two or more maternally related males, and (3) in affected males, after infection by Epstein-Barr virus, infected B cells grow spontaneously, saliva transforms cord lymphocytes, and Epstein-Barr virus antibody is usually absent in serums.  By studying affected patients and their families, we seek to increase knowledge
Damp housing and asthma: a case-control study
Authors: I. J. Williamson, C. J. Martin, G. McGill, R. D. Monie, A. G. Fennerty
Journal: Thorax (1997)

BACKGROUND: Several epidemiological studies have reported a higher prevalence of respiratory symptoms in subjects living in damp housing, but links with specific respiratory diseases such as asthma have not been satisfactorily established. METHODS: One hundred and two subjects with physician diagnosed asthma and 196 age and sex matched controls were interviewed; 222 (75%) then agreed to have their dwelling surveyed for dampness. The prevalence of both self-reported and observed dampness in the homes of the asthmatic subjects and controls were compared. Both asthma and the severity of the dampness were quantified so that the possibility of a dose-response relationship could be investigated. RESULTS: Asthmatic subjects reported dampness in their current (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.18 to 3.12) and previous (OR 2.11, 95% CI 1.29 to 3.47) dwellings more frequently than control subjects. The surveyor confirmed dampness in 58 of 90 (64%) dwellings of asthmatic subjects compared with 54 of 132 (41%) dwellings of control subjects (OR 2.62, 95% CI 1.50 to 4.55). This association persisted after controlling for socioeconomic and other confounding variables (adjusted OR 3.03, 95% CI 1.65 to 5.57). The severity of asthma was found to correlate statistically with measures of total dampness (r = 0.30, p = 0.006) and mould growth (r = 0.23, p = 0.035) in the dwelling. Patients living in homes with confirmed areas of dampness had greater evidence of airflow obstruction than those living in dry homes (mean difference in forced expiratory volume in one second (FEV1) 10.6%, 95% CI 1.0 to 20.3). CONCLUSIONS: Asthma is associated with living in damp housing and there appears to be a dose-response relationship. Action to improve damp housing conditions may therefore favourably influence asthma morbidity.
A road map for efficient and reliable human genome epidemiology
Authors: John P A Ioannidis, Marta Gwinn, Julian Little, Julian P T Higgins, Jonine L Bernstein, Paolo Boffetta, Melissa Bondy, Molly S Bray, Paul E Brenchley, Patricia A Buffler, Juan Pablo Casas, Anand Chokkalingam, John Danesh, George Davey Smith, Siobhan Dolan, Ross Duncan, Nelleke A Gruis, Patricia Hartge, Mia Hashibe, David J Hunter, Marjo-Riitta Jarvelin, Beatrice Malmer, Demetrius M Maraganore, Julia A Newton-Bishop, Thomas R O'Brien, Gloria Petersen, Elio Riboli, Georgia Salanti, Daniela Seminara, Liam Smeeth, Emanuela Taioli, Nic Timpson, Andre G Uitterlinden, Paolo Vineis, Nick Wareham, Deborah M Winn, Ron Zimmern, Muin J Khoury
Journal: Nature Genetics (2006)
Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer
Authors: John R. Eckardt, Joachim von Pawel, Jean-Louis Pujol, Zsolt Papai, Elisabeth Quoix, Andrea Ardizzoni, Ruth Poulin, Alaknanda J. Preston, Graham Dane, Graham Ross
Journal: Journal of Clinical Oncology (2007)

Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status < or = 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of > or = 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral -IV) of -3.6% (95% CI, -12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
Parameters recorded by software of non-invasive ventilators predict COPD exacerbation: a proof-of-concept study
Authors: J.-C. Borel, J. Pelletier, N. Taleux, A. Briault, N. Arnol, C. Pison, R. Tamisier, J.-F. Timsit, J.-L. Pepin
Journal: Thorax (2015)

To assess whether daily variations in three parameters recorded by non-invasive ventilation (NIV) software (respiratory rate (RR), percentage of respiratory cycles triggered by the patient (%Trigg) and NIV daily use) predict the risk of exacerbation in patients with chronic obstructive pulmonary disease (COPD) treated by home NIV.Patients completed the EXACT-Pro questionnaire daily to detect exacerbations. The 25th and 75th percentiles of each 24 h NIV parameter were calculated and updated daily. For a given day, when the value of any parameter was >75th or <25th percentile, the day was marked as 'abnormal value' ('high value' >75th, 'low value' <25th). Stratified conditional logistic regressions estimated the risk of exacerbation when ≥2 days (for RR and %Trigg) or ≥3 days (for NIV use) out of five had an 'abnormal value'.Sixty-four patients were included. Twenty-one exacerbations were detected and medically confirmed. The risk of exacerbation was increased when RR (OR 5.6, 95% CI 1.4 to 22.4) and %Trigg (OR 4.0, 95% CI 1.1 to 14.5) were considered as 'high value' on ≥2 days out of five.This proof-of-concept study shows that daily variations in RR and %Trigg are predictors of an exacerbation.
STRESS, FATIGUE, HEALTH, AND RISK OF ROAD TRAFFIC ACCIDENTS AMONG PROFESSIONAL DRIVERS: The Contribution of Physical Inactivity
Authors: Adrian H. Taylor, Lisa Dorn
Journal: Annual Review of Public Health (2005)

▪ Abstract Strategies to achieve ambitious targets for reducing road accidents ( 34 ) have largely focused on engineering and technological advancements, the modification of occupational demands, and, to a lesser extent, human factors. These factors include stress and psychological states; sleep, fatigue, and alertness; and health status. Physical activity appears to influence all these human factors but has not previously been systematically considered as a direct or indirect risk factor for driver accidents. This chapter provides an overview, within an evidence-based framework, of the impact each of these human factors has on driver performance and risk of at-work road traffic accidents and then examines how physical (in)activity may moderate and mediate these relationships. Finally, we consider practical implications for work site interventions. The review aims to offer an evidence base for the deployment of resources to promote physical activity, manage stress, facilitate sleep, reduce fatigue, and enhance alertness to improve physical and psychological health among professional drivers.