tbuckley/cabot-search huggingface dataset:
Comparison of Error Rates in Single-Arm Versus Randomized Phase II Cancer Clinical Trials
Authors: Hui Tang, Nathan R. Foster, Axel Grothey, Stephen M. Ansell, Richard M. Goldberg, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2010)

PURPOSE To improve the understanding of the appropriate design of phase II oncology clinical trials, we compared error rates in single-arm, historically controlled and randomized, concurrently controlled designs. PATIENTS AND METHODS We simulated error rates of both designs separately from individual patient data from a large colorectal cancer phase III trials and statistical models, which take into account random and systematic variation in historical control data. RESULTS In single-arm trials, false-positive error rates (type I error) were 2 to 4 times those projected when modest drift or patient selection effects (eg, 5% absolute shift in control response rate) were included in statistical models. The power of single-arm designs simulated using actual data was highly sensitive to the fraction of patients from treatment centers with high versus low patient volumes, the presence of patient selection effects or temporal drift in response rates, and random small-sample variation in historical controls. Increasing sample size did not correct the over optimism of single-arm studies. Randomized two-arm design conformed to planned error rates. CONCLUSION Variability in historical control success rates, outcome drifts in patient populations over time, and/or patient selection effects can result in inaccurate false-positive and false-negative error rates in single-arm designs, but leave performance of the randomized two-arm design largely unaffected at the cost of 2 to 4 times the sample size compared with single-arm designs. Given a large enough patient pool, the randomized phase II designs provide a more accurate decision for screening agents before phase III testing.
German Textbook of Genetics
Authors: J. H. Renwick
Journal: BMJ (1962)

Polycystic kidney disease (PKD) is a lethal disorder characterized by progressive expansion of renal cysts. Genetic mutations associated with PKD are thought to disrupt intracellular Ca<sup>2+</sup> regulation, leading to abnormal proliferation of tubule epithelial cells. cAMP stimulates the B-Raf/MEK/extracellular signal-regulated kinase (B-Raf/MEK/ERK) pathway and accelerates the proliferation of cells that are cultured from PKD cysts. By contrast, cAMP inhibits the proliferation of cells from normal human kidneys (NHK) and M-1 mouse collecting duct cells. Previously, it was found that a sustained reduction of intracellular Ca<sup>2+</sup> levels in NHK and M-1 cells that were treated with Ca<sup>2+</sup> entry blockers allowed cAMP activation of the B-Raf/MEK/ERK pathway, switching the cells to a cAMP-growth stimulated phenotype. In this study, primary cultures of cyst epithelial cells from autosomal dominant (ADPKD) and recessive (ARPKD) PKD kidneys were used to determine whether controlled addition of Ca<sup>2+</sup> could reverse the aberrant mitogenic response to cAMP. Steady-state intracellular Ca<sup>2+</sup> levels were found to be 20 nM lower in cyst-derived ADPKD cells (57 ± 2 nM) compared with NHK cells (77 ± 2 nM). Treatment of ADPKD cells or ARPKD cells with either Bay K8644, a Ca<sup>2+</sup> channel activator, or A23187, a Ca<sup>2+</sup> ionophore, caused sustained increases in intracellular Ca<sup>2+</sup> levels and completely reversed the mitogenic response to cAMP. Elevation of intracellular Ca<sup>2+</sup> levels in ADPKD cells increased Akt activity and blocked cAMP-dependent B-Raf and ERK activation. Thus, increases in [Ca<sup>2+</sup>]<sub>i</sub> are able to restore the normal anti-mitogenic response to cAMP in cells that are derived from two genetically distinct forms of PKD.
Diagnosis-Related Groups, Severity of Illness, and Equitable Reimbursement Under Medicare
Authors: Barry S. Eisenberg
Journal: JAMA (1984)

The art and science of case-mix severity of illness measures has recently been forced into the forefront of health service policy and reimbursement discussions by enactment and implementation of Public Law 98-21, the Prospective Payment System for Hospitals. This law and its accompanying proposed regulations, released by the Health Care Financing Administration (HCFA) on Sept 1, 1983, instituted the diagnosis-related group (DRG) classification and reimbursement system for payment of inpatient hospital care for Medicare beneficiaries.<sup>1,2</sup>The DRG system is, essentially, a case-mix reimbursement system that, theoretically, reimburses hospitals for treating patients based on the average amount of hospital resources used in treating a patient within a particular diagnostic category. While the DRG regulations recognize that there will be variations in severity within each of the 467 diagnostic categories, it is reasoned that as long as hospitals are reimbursed on a "meaningful" average and enough cases within each DRG category
Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats
Authors: P. Janiak, B. Poirier, J.-P. Bidouard, C. Cadrouvele, F. Pierre, L. Gouraud, I. Barbosa, J. Dedio, J.-P. Maffrand, G. Le Fur, S. O'Connor, J.-M. Herbert
Journal: Kidney International (2007)
Israeli surgeons implant first permanent artificial ventricle
Authors: J. Siegel-Itzkovich
Journal: BMJ (2000)

Surgeons who implanted the first permanent artificial left ventricle in a patient are confident that the tiny device will eventually be used in most heart transplantations around the world. The 64 year old patient was terminally ill when he received the implant, having experienced severe heart problems for several months, and he died five days later on 1 August of multiple organ failure. His own heart had been working at only 10% capacity at the time of the implant.

Dr Jacob Lavee, head of the department of cardiothoracic surgery at the Sheba Hospital, near Tel Aviv, performed …
Chernobyl fallout and outcome of pregnancy in Finland.
Authors: A Auvinen, M Vahteristo, H Arvela, M Suomela, T Rahola, M Hakama, T Rytömaa
Journal: Environmental Health Perspectives (2001)

Possible effects of Chernobyl fallout on outcome of pregnancy in Finland were evaluated in a nationwide follow-up study. The outcomes were the rate of live births and stillbirths, pregnancy loss, and induced abortions by municipality. Exposure was assessed based on nationwide surveys of radiation dose rate from the Chernobyl fallout, from both external and internal exposures. Using these measurements, we estimated the monthly dose rate for each of the 455 Finnish municipalities. On average, the dose rate from Chernobyl fallout reached 50 microSv per month in May 1986--a doubling of the natural background radiation. In the most heavily affected area, 4 times the normal background dose rates were recorded. Given the underlying regional differences in live birth, stillbirth, and abortion rates, we used longitudinal analysis comparing changes over time within municipalities. A temporary decline in the live birth rate had already begun before 1986, with no clear relationship to the level of fallout. A statistically significant increase in spontaneous abortions with dose of radiation was observed. No marked changes in induced abortions or stillbirths were observed. The decrease in the live birth rate is probably not a biological effect of radiation, but more likely related to public concerns of the fallout. The effect on spontaneous abortions should be interpreted with caution, because of potential bias or confounding. Further, there is little support in the epidemiologic literature on effects of very low doses of radiation on pregnancy outcome.
AAV transcytosis through barrier epithelia and endothelium
Authors: Giovanni Di Pasquale, John A. Chiorini
Journal: Molecular Therapy (2005)

To transduce efficiently barrier epithelia such as the lung is the goal of several gene therapy applications. However, experiments with AAV-2 suggest that transduction is limited in this type of barrier epithelia. In contrast, other serotypes of AAV transduce barrier epithelia and exhibit broad dissemination throughout the tissue. Transcytosis is a process by which proteins and pathogens overcome barrier layers to reach the opposite cell surface. To understand better the entry pathway of AAV particles and their ability to penetrate barrier epithelia, we tested the hypothesis that the limited transduction of some barrier epithelia in vitro or the spread of some AAV serotypes through tissue in vivo is due to transcytosis. Our experiments demonstrate that dependoviruses can penetrate barrier cells by transcytosis. The process is rapid as well as serotype and cell-type specific and can be blocked by neutralizing antibodies, temperature, or chemical inhibitors of transcytosis. The particles isolated following apical-to-basolateral transport are still encapsulated and they can transduce permissive cell lines in vitro. Furthermore, the entry pathway used by AAV-5 for transcytosis appears to be independent of the one used for transduction. Importantly, inhibition of virus transcytosis results in a dramatic increase in intracellular vector and transduction.
Head-to-Head Comparison of Serial Soluble ST2, Growth Differentiation Factor-15, and Highly-Sensitive Troponin T Measurements in Patients With Chronic Heart Failure
Authors: Hanna K. Gaggin, Jackie Szymonifka, Anju Bhardwaj, Arianna Belcher, Benedetta De Berardinis, Shweta Motiwala, Thomas J. Wang, James L. Januzzi
Journal: JACC Heart Failure (2014)
Statins as adjunct therapy in COPD: how do we cope after STATCOPE?
Authors: Robert P Young, Raewyn J Hopkins, Alvar Agusti
Journal: Thorax (2014)

Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are widely used to reduce cardiovascular (CVS) disease risk yet have pleiotropic effects in other organs, including the lungs.1 ,2 The results of the Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) study, that investigated their potential effects on exacerbations of COPD, have been recently published in the New England Journal of Medicine .3 In this Hot off the breath editorial, we review the rationale for the study, discuss its design, main results, strengths and limitations, and speculate on the future of statins in COPD.

Statins reduce the recruitment of neutrophils and macrophages into the lung, alter bronchial remodelling, prevent emphysema and reduce systemic inflammation.1 ,2 ,4 These biological effects appear to have clinical relevance as observational studies in COPD patients report reduced all-cause mortality,5–8 reduced mortality from acute exacerbations,8–10 reduced frequency of COPD exacerbations,8 ,11–13 and reduced decline of lung function,14 for those taking statins, as compared to not taking them.

In one small randomised controlled trial (RCT), statin use in COPD patients was associated with a clinically significant increase in exercise tolerance, although this benefit was limited to those in whom baseline C-reactive protein (CRP) was elevated (ie, those with evidence of systemic inflammation).15 To date, STATCOPE is the only RCT that has assessed the effect of adjunct statin treatment prospectively on acute exacerbations in COPD in a large cohort of patients.3

STATCOPE was a large, randomised, multicentre, double-blind, placebo-controlled trial of simvastatin (40 mg/day) in the prevention of COPD exacerbations in patients with moderate-to-severe COPD (N=885).3 Importantly, patients with diabetes or CVS disease (figure 1), those already on statins, or those that required statins based on accepted CVS risk criteria, were excluded. The …
A COMPARISON OF THE TEST PERFORMANCES OF THE BRAIN-INJURED AND THE BRAIN-DISEASED
Authors: ROBERT M. ALLEN
Journal: American Journal of Psychiatry (1949)

This paper is the fourth in a series dealing with encephalopathy due to brain injury and brain disease. The test results indicate that the functioning and efficiency of the patients in both groups follow a similar pattern: full scale IQ's within the normal limits, verbal scores significantly higher than performance ratings, and low intergroup differences for full scale, verbal, and performance scales. The brain-injured patients, on the average, showed more marked discrepancies between the verbal and performance subtests. The functions that are impaired or inefficient are discussed. The author holds that the statistical findings do not fully justify the quantitative interpretation that such rigid constructs as mathematical limits would imply. The effects of an encephalopathic process are serious but an unmeasurable consideration must be given to the impact upon the personality structure of the patient. It is questionable whether any statistical technique exists at present which could factor out this pervasive element satisfactorily. A comparison of the performances of both groups on the Bellevue Intelligence Scale shows similar function losses in addition to a consistent mean subtest weighted score pattern. For those interested in designing scatter-patterns the procedure suggested previously (1, p. 230) still holds: use information weighted score as the basal point for deviation computation of the other 10 subtest weighted scores. The order of deviation of these 10 subtests from information —from most to least deviated—is: digit symbol, digit span, block design, object assembly, and picture arrangement.
Gallium-Avid Painless Thyroiditis in a Patient With AIDS
Authors: DWIGHT M. ACHONG, KENNETH J. SNOW
Journal: Clinical Nuclear Medicine (1994)

Intense thyroidal Ga-67 accumulation was seen in a man with AIDS imaged for suspected Pneumocystis carinii pneumonia. Concurrent Tc-99m pertechnetate thyroid scanning demonstrated absent trapping, helping establish the diagnosis of painless thyroiditis. Occult hyperthyroidism, and not pulmonary infection, may have been responsible for the patient's original presenting symptoms.
Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy
Authors: Philippe Moreau, Thierry Facon, Xavier Leleu, Nadine Morineau, Pauline Huyghe, Jean-Luc Harousseau, Régis Bataille, Hervé Avet-Loiseau
Journal: Blood (2002)
Paraspinal Abscess Complicating Facet Joint Injection
Authors: MICHAEL MAGEE, SIRI KANNANGARA, BRUCE DENNIEN, ROBERT LONERGAN, LOUISE EMMETT, HANS VAN DER WALL
Journal: Clinical Nuclear Medicine (2000)

A 58-year-old man had severe lower back pain after minor trauma. This was initially treated with simple analgesics but with little effect. He was referred for injection of betamethasone and lignocaine into the left iliolumbar angle, which was followed by immediate relief of pain. One week later, he was hospitalized for worsening back pain, fever, and night sweats. Results of plain radiographs of the lumbar spine were reported as normal. Scintigraphy was consistent with a paraspinal abscess, which was confirmed on CT, MRI, and blood cultures. Blood cultures obtained at the time of admission grew Staphylococcus aureus, which was sensitive to methicillin. The patient responded to intravenous antibiotics.
Flow cytometric DNA-ploidy and proliferative activity of diethylnitrosamine-induced hepatocellular carcinoma and pulmonary metastases in monkeys
Authors: Károly Lapis, József Bocsi, Péter Lapis, Unnur P. Thorgeirsson
Journal: Hepatology (1995)

Flow cytometric DNA analysis was carried out on diethylnitrosamine (DEN) induced primary hepatocellular carcinomas (HCC) and lung metastases in monkeys. In analyzing one sample from each of 113 HCC cases, 76 (67.2%) were diploid and 37 (32.7%) aneuploid. When more samples were analyzed from the same tumorous liver, all of the 76 diploid cases maintained their pattern, whereas 5 (13.5%) of the aneuploid cases displayed both diploid and aneuploid DNA. Studies of lung metastases from 44 (28 diploid, 16 aneuploid) HCC cases showed that the DNA-ploidy pattern characterizing the primary HCC was preserved in the metastases in 78.6% of the diploid and 93.7% of the aneuploid cases. The average synthetic phase fraction (SPF) value for the diploid tumors was 7.7% and the aneuploid tumors 14.9%. The difference is highly significant (P < .01). Highly significant correlation was found between the DNA ploidy and the SPF values, both in the primary HCC (P = .0001) and the metastases (P = .0266). Of different tumor and host features examined, statistically significant correlation was only found between DNA-ploidy/SPF and the cytological tumor grade. This study represents the first DNA-ploidy analysis of HCC in monkeys. The data showed that diploid and aneuploid tumors displayed comparable metastatic potential. The DNA-ploidy pattern was preserved in the metastases in the majority of the cases. (Hepatology 1995; 22:952–961.)
MHC class I/II deficient NOG mice are useful for analysis of human T/B cell responses for human tumor immunology research
Authors: Tomonori Yaguchi, Asuka Kobayashi, Ikumi Katano, Yuyo Ka, Mamoru Ito, Yutaka Kawakami
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Immunologically humanized mice are promising tools to analyze in vivo human anit-tumor immune responses. When human PBMCs are transferred into NOG (NOD/Shi-scid IL2rγnull) mice, severe GVHD developed in a couple of weeks hinders long term detailed analysis of human immune
Bullous eosinophilic cellulitis associated with ulcerative colitis: effective treatment with sulfasalazine and glucocorticoids
Authors: J. Utikal, W.K. Peitsch, N. Kemmler, N. Booken, R. Hildenbrand, R. Gladisch, S. Goerdt, M. Goebeler
Journal: British Journal of Dermatology (2007)

Journal Article Bullous eosinophilic cellulitis associated with ulcerative colitis: effective treatment with sulfasalazine and glucocorticoids Get access J. Utikal, J. Utikal Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar W.K. Peitsch, W.K. Peitsch Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar N. Kemmler, N. Kemmler Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar N. Booken, N. Booken Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar R. Hildenbrand, R. Hildenbrand Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar R. Gladisch, R. Gladisch 4th Medical Department, University Medical Center Mannheim, Ruprecht‐Karl University of Heidelberg, Theodor‐Kutzer‐Ufer 1–3, D‐68135 Mannheim, Germany E‐mail: jochen.utikal@haut.ma.uni‐heidelberg.de Search for other works by this author on: Oxford Academic Google Scholar S. Goerdt, S. Goerdt Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar M. Goebeler M. Goebeler Department of Dermatology, Venereology and Allergology, Department of Pathology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 4, 1 April 2007, Pages 764–766, https://doi.org/10.1111/j.1365-2133.2006.07729.x Published: 01 April 2007
Gastric Mucosal Damage Caused by Monochloramine in the Rat and Protective Effect of Taurine: Endoscopic Observation Through Gastric Fistula
Authors: M. Kodama, H. Tsukada, M. Ooya, M. Onomura, T. Saito, K. Fukuda, H. Nakamura, T. Taniguchi, M. Tominaga, M. Hosokawa, J. Fujita, Y. Seino
Journal: Endoscopy (2000)

Background and Study Aims: The mechanism of Helicobacter pylori-induced gastric mucosal injury is unknown, but H. pylori infection is conducive to accumulation in the stomach of monochloramine, a cytotoxic substance. The present study involved morphological investigation of the damaging effects of monochloramine on rat gastric mucosa, using endoscopic observations through a gastric fistula. The study also examined the protective effect of taurine against monochloramine-induced gastric mucosal lesions in rats.
Double Tachycardia—Clinical Features.
Authors: Stanley H. Wishner
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Double Tachycardia—Clinical Features.Stanley H. Wishner, M.D., John A. Kastor, M.D., Peter M. Yurchak, M.D.Stanley H. Wishner, M.D.Search for more papers by this author, John A. Kastor, M.D.Search for more papers by this author, Peter M. Yurchak, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-823_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEleven cases of double tachycardia were encountered, 10 in the last year. The high incidence prompted a review of records and electrocardiograms. Criteria were atrioventricular dissociation and ectopic accelerated pacemakers controlling atria and ventricles. The atrial mechanism in 10 of 11 cases was atrial tachycardia and 1 of 11, atrial flutter. The ventricular mechanism in five was junctional tachycardia only, and six had junctional or ventricular mechanisms, or both, alternatively. Diagnosis was often delayed because of lack of appreciation of AV dissociation and failure to recognize atrial mechanism. The clinical features were striking. All but three patients were over 60... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Stanley H. Wishner, M.D.; John A. Kastor, M.D.; Peter M. Yurchak, M.D.Affiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 823-823KeywordsElectrocardiographyPacemakersTachycardia ePublished: 1 December 2008 Issue Published: 1 May 1971 PDF downloadLoading ...
Relief of induced itch with a novel local anaesthetic mixture
Authors: R. Marks, D. Shuttleworth, S. Hill, D.M. Conelly
Journal: British Journal of Dermatology (1988)

Journal Article Relief of induced itch with a novel local anaesthetic mixture Get access R. Marks, R. Marks Department of Medicine (Dermatology), University of Wales College of Medicine, Cardiff Search for other works by this author on: Oxford Academic Google Scholar D. Shuttleworth, D. Shuttleworth Department of Medicine (Dermatology), University of Wales College of Medicine, Cardiff Search for other works by this author on: Oxford Academic Google Scholar S. Hill, S. Hill Department of Medicine (Dermatology), University of Wales College of Medicine, Cardiff Search for other works by this author on: Oxford Academic Google Scholar D.M. Conelly D.M. Conelly Astra Pharmacauticals Ltd., King's Langley Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue s33, 1 July 1988, Pages 19–20, https://doi.org/10.1111/j.1365-2133.1988.tb05343.x Published: 01 July 1988