tbuckley/cabot-search huggingface dataset:
Outcome-Adaptive Randomization: Is It Useful?
Authors: Edward L. Korn, Boris Freidlin
Journal: Journal of Clinical Oncology (2010)

Outcome-adaptive randomization is one of the possible elements of an adaptive trial design in which the ratio of patients randomly assigned to the experimental treatment arm versus the control treatment arm changes from 1:1 over time to randomly assigning a higher proportion of patients to the arm that is doing better. Outcome-adaptive randomization has intuitive appeal in that, on average, a higher proportion of patients will be treated on the better treatment arm (if there is one). In both the randomized phase II and phase III settings with a short-term binary outcome, we compare outcome-adaptive randomization with designs that use 1:1 and 2:1 fixed-ratio randomizations (in the latter, twice as many patients are randomly assigned to the experimental treatment arm). The comparisons are done in terms of required sample sizes, the numbers and proportions of patients having an inferior outcome, and we restrict attention to the situation in which one treatment arm is a control treatment (rather than the less common situation of two experimental treatments without a control treatment). With no differential patient accrual rates because of the trial design, we find no benefits to outcome-adaptive randomization over 1:1 randomization, and we recommend the latter. If it is thought that the patient accrual rates will be substantially higher because of the possibility of a higher proportion of patients being randomly assigned to the experimental treatment (because the trial will be more attractive to patients and clinicians), we recommend using a fixed 2:1 randomization instead of an outcome-adaptive randomization.
Delitto Perfetto: foreign DNA disappears without a trace.
Authors: Jennifer Medlin
Journal: Environmental Health Perspectives (2002)

A group of NIEHS scientists has recently perfected a new in vivo gene modification technique that enables scientists to quickly generate site-directed mutations onto specific regions of the yeast genome. The researchers were able to create genetic mutations by inserting foreign DNA into host DNA without leaving a trace of the foreign DNA. Dubbed "Delitto Perfetto," Italian for "perfect murder," the new technique leaves behind no clue that foreign DNA was introduced to engineer the desired genetic changes. It could transform the way genetic researchers analyze how genes function and respond to human disease and environmental influences.
Brain Death—An Opposing Viewpoint
Authors: Paul A. Byrne
Journal: JAMA (1979)

Recent and proposed legislation to establish "brain-related" criteria of death has uniformly confounded irreversible cessation of total brain function with the death of the human person. Much of the confusion comes from widespread misunderstanding of how the word "death" is used and what it means. Cessation of total brain function, whether irreversible or not, is not necessarily linked to total destruction of the brain or to the death of the person. Further, to take vital organs or to otherwise treat people as though they were dead already on the basis of these recent criteria is morally unacceptable to most Orthodox Jews and Christians.
Choosing a career
Authors: J. Bache
Journal: BMJ (1999)

Few qualifications can result in such a wide range of career choices as a medical degree, but how do you decide on your final career? Is it right to enter medical school wanting to be a neurosurgeon and refusing to consider any other possibility? Should you dedicate your life to paediatrics because of one tremendously enthusiastic consultant? Equally, should you eliminate radiology because of a particularly uninspiring consultant? Do you enjoy all specialties but drift fairly aimlessly from one post to another? Do you feel like a square peg in a round hole? What factors should you consider when making your choice?

Each individual must find a unique answer to these questions, but some general comments may be useful. Remember that one man's meat is another man's poison. We are all individuals, with our own strengths and weaknesses and our own likes and dislikes. The world would be a boring place if it were otherwise.

### Medicine is a broad church …
A CROSS-CULTURAL APPROACH TO MENTAL HEALTH PROBLEMS
Authors: E. D. WITTKOWER, J. FRIED
Journal: American Journal of Psychiatry (1959)

There are many ways of viewing the etiology of mental disease. It can be understood as being due to heredity, due to fixation at infantile levels of instinctual development and faulty early object relationships, due to biological dysfunctions and due to influences arising from interpersonal relationships within the society or culture in which an individual lives. None of these viewpoints is "wrong" but each represents a segmental view of a multilateral process. In the foregoing an attempt has been made to survey our present knowledge regarding the relevance of social and cultural factors to the etiology and treatment of mental illness. In this survey which inevitably had to be incomplete many questions have been raised and few have been answered. It has been shown that the major categories of mental disorders occur ubiquitously, that there is some evidence that they are distributed unevenly, that nosological differences exist between different cultural areas and that differences both in frequency and in nature of clinical manifestations can be related to cultural differences. Methodological difficulties especially of comparative quantitative studies but also of qualitative studies have been pointed out.
348 Human umbilical cord (HUC) and HUC blood CD105-positive cells can differentiate in vitro into hepatocyte-like cells
Authors: P. Burra, A. Masier, M. Turetta, C. Calore, R. Di Liddo, P. Boa, S. Tomat, E.P. Russo, M.T. Conconi, P.P. Parnigotto
Journal: Journal of Hepatology (2006)
On the Clinical Confusion between Distension of the Gall Bladder and Movable Kidney
Authors: H. Morris
Journal: BMJ (1895)

small quantity, 2 or 3 ounces a day.She at once lost the irritation of skin, had good nights, to which she had long been a stranger, enjoyed her food, and gained flesh.The subsequent course of this case is most peculiar and difficult to explain.Two points became clear.She at once lost almost completely
Oxidized Low-Density Lipoprotein Induces Apoptosis of Human Endothelial Cells by Activation of CPP32-Like Proteases
Authors: Stefanie Dimmeler, Judith Haendeler, Jan Galle, Andreas M. Zeiher
Journal: Circulation (1997)

Background Oxidized LDL (oxLDL) is believed to play a key role as a triggering molecule that causes injury to the endothelium as an early event in atherogenesis. However, the mechanisms by which oxLDL injures endothelial cells are entirely unknown. We speculate that oxLDL may activate a cellular suicide pathway that leads to apoptosis. Methods and Results Human umbilical venous endothelial cells (HUVEC) were incubated with increasing doses of native or oxLDL for 18 hours. Apoptosis of HUVEC was measured with an ELISA specific for histone-associated DNA fragments and confirmed with DNA laddering. Native LDL had no effect, but incubation with oxLDL dose-dependently induced apoptosis of HUVEC. Induction of apoptosis by oxLDL was associated with increased CPP32-like protease activity, which is the major enzyme that initiates the proteolytical cascade leading to cell death. Specific inhibition of CPP32 activity completely abrogated oxLDL-induced apoptosis. The antioxidants N -acetylcysteine and the combination of vitamins C and E prevented oxLDL-induced apoptosis, abrogated the enhancement of CPP32-like protease activity, and inhibited the proteolytic cleavage of CPP32 into its active subunit p17. Conclusions oxLDL activates the suicide pathway leading to apoptosis of endothelial cells by enhancing CPP32-like protease activity. The oxLDL-mediated activation of CPP32 appears to involve the elaboration of reactive oxygen species. Activation of the cell death effector CPP32 by oxLDL may provide a mechanistic clue to the “response-to-injury” hypothesis of atherogenesis.
WHAT CAN BE ACCOMPLISHED BY TREATMENT OF EUSTACHIAN TUBE, WITH SPECIAL CONSIDERATION OF THE TREATMENT OF CHRONIC STENOSIS.
Authors: GEORGE MORLEY MARSHALL
Journal: JAMA (1898)

Let us briefly recall the anatomy and function of the Eustachian tube, in so far as it concerns the measures advocated in this paper. The Eustachian tube is the passage between the naso-pharynx and tympanic cavity—in length thirty-three to forty millimeters. From its relatively large pharyngeal mouth it extends twenty-five millimeters with walls formed by an incomplete furrow of fibro-cartilage, consisting of a posterior and anterior plate, the anterior being movable. This portion of the tube where not cartilaginous is membranous, which with its lining mucous membrane has considerable thickness. This cartilaginous portion of the tube unites with the remaining ten to fifteen millimeters of the osseous portion of the tube, forming with it an obtuse somewhat circular angle of 135 degrees. At this angle the lumen of the tube is smallest; that is two to three millimeters. The walls of the Eustachian tube are lined by glandular mucous membrane,
Menopausal Status and Sleep-disordered Breathing in the Wisconsin Sleep Cohort Study
Authors: Terry Young, Laurel Finn, Diane Austin, Andrea Peterson
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Menopause is considered to be a risk factor for sleep-disordered breathing, but this hypothesis has not been adequately tested. The association of premenopause, perimenopause, and postmenopause with sleep-disordered breathing was investigated with a population-based sample of 589 women enrolled in the Wisconsin Sleep Cohort Study. Menopausal status was determined from menstrual history, gynecologic surgery, hormone replacement therapy, follicle-stimulating hormone, and vasomotor symptoms. Sleep-disordered breathing was indicated by the frequency of apnea and hypopnea events per hour of sleep, measured by in-laboratory polysomnography. Multivariable logistic regression was used to estimate odds ratios for having 5 or more and 15 or more apnea and hypopnea events per hour. Odds ratios (95% confidence interval), adjusted for age, body habitus, smoking, and other potential confounding factors, for 5 or more apnea and hypopnea events per hour were 1.2 (0.7, 2.2) with perimenopause and 2.6 (1.4, 4.8) with postmenopause; odds ratios for 15 or more apnea and hypopnea events per hour were 1.1 (0.5, 2.2) with perimenopause and 3.5 (1.4, 8.8) with postmenopause. The menopausal transition is significantly associated with an increased likelihood of having sleep-disordered breathing, independent of known confounding factors. Evaluation for sleep-disordered breathing should be a priority for menopausal women with complaints of snoring, daytime sleepiness, or unsatisfactory sleep.
Multiple crashes on motor ways.
Authors: J A Frais
Journal: BMJ (1972)

troduction of modern, malleable fibre-optic endoscopes has been accompanied by a fall in the incidence of oesophageal injuries.However, even the most skilled endoscopist using the latest apparatus must still be ever awake to the risk of oesophageal damage."Smith and Tanner's' figure of one per- foration in every 300 gastroscopies and one perforation in every 100 oesophagoscopies refers to the use of rigid instruments; Arigae collected information on 123,900 gastro- scopies.The perforation rate with rigid in- struments was 0-065 % and with early fibre- scopes 0 03%.Its apparent safety is con- tributing to the rapid increase in the num- ber of fibre-endoscopies being performed in patients of all ages by endoscopists of varied experience.Instruments are becoming more complex and investigators more ambitious.It is therefore important to obtain accurate and up-to-date knowledge of the incidence of all the complications of modem fibre- endoscopy.We hope that this information will shortly be available from a survey being undertaken among members of the British Society for Digestive Endoscopy.-Weare, etc.,
Toll-Like Receptors 4 and 5 Induce Distinct Types of Vasculitis
Authors: Jiusheng Deng, Wei Ma-Krupa, Andrew T. Gewirtz, Brian R. Younge, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Circulation Research (2009)

Large vessel vasculitides, such as Takayasu arteritis and giant cell arteritis, affect vital arteries and cause clinical complications by either luminal occlusion or vessel wall destruction. Inflammatory infiltrates, often with granulomatous arrangements, are distributed as a panarteritis throughout all of the artery's wall layers or cluster in the adventitia as a perivasculitis. Factors determining the architecture and compartmentalization of vasculitis are unknown. Human macrovessels are populated by indigenous dendritic cells (DCs) positioned in the adventitia. Herein, we report that these vascular DCs sense bacterial pathogens and regulate the patterning of the emerging arteritis. In human temporal artery-SCID chimeras, lipopolysaccharides stimulating Toll-like receptor (TLR)4 and flagellin stimulating TLR5 trigger vascular DCs and induce T-cell recruitment and activation. However, the architecture of the evolving inflammation is ligand-specific; TLR4 ligands cause transmural panarteritis and TLR5 ligands promote adventitial perivasculitis. Underlying mechanisms involve selective recruitment of functional T cell subsets. Specifically, TLR4-mediated DC stimulation markedly enhances production of the chemokine CCL20, biasing recruitment toward CCL20-responsive CCR6(+) T cells. In adoptive transfer experiments, CCR6(+) T cells produce an arteritis pattern with media-invasive T cells damaging vascular smooth muscle cells. Also, CCR6(+) T cells dominate the vasculitic infiltrates in patients with panarteritic giant cell arteritis. Thus, depending on the original danger signal, vascular DCs edit the emerging immune response by differentially recruiting specialized T effector cells and direct the disease process toward distinct types of vasculitis.
Association of maternal anti‐<scp>HLA</scp> class <scp>II</scp> antibodies with protection from allergy in offspring
Authors: M. Jones, H. Jeal, J. M. Harris, J. D. Smith, M. L. Rose, A. N. Taylor, P. Cullinan
Journal: Allergy (2013)

Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years.Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age.Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order.This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy.
Relationship of acute obstructive airway change to chronic (fixed) obstruction.
Authors: M R Becklake
Journal: Thorax (1995)

In this report of a 5-yr longitudinal study of workers at six cotton textile mills, exposure and across- shift FEV, changes were evaluated as possible predictors of the annual change in FEV, for yarn manufacturing workers.A total of 611 workers had three repeatable spirometric tests, over at least 3yr, and at least one (average of three) across-shift test, while always working the same shift.The "same shift" criterion controlled for the effect of diurnal variation.Average exposure was determined from measures of lint-free elutriated cotton dust in combination with job histories.This study found a significant association between the acute and chronic effects of cotton dust exposure.Both exposure and across-shift change proved to be significant predictors of annual change, and excess annual declines in FEV, were predicted even for exposures of 200pg/m3 and across-shift drops in FEV, of 200 ml.These results suggest that, to prevent dust-related chronic decline in lung function, current smokers should be excluded from yarn manufacturing work and exposure should be reduced below 200 pgi/m3, to
Protecting Confidentiality in Epidemiologic Investigations by the Centers for Disease Control
Authors: William J. Curran
Journal: New England Journal of Medicine (1986)

THE Centers for Disease Control (CDC) in Atlanta, Georgia, a part of the United States Public Health Service, is one of the nation's primary resources for epidemiologic investigations. Much of the work of the CDC is conducted in cooperation with state health departments; together, these agencies collect a large amount of information from a variety of sources. Within the limits of the freedom of information laws, the CDC makes a substantial effort to maintain the confidentiality of personal records and personal identities in its investigational work.The protection of personal confidentiality and privacy in CDC records has rarely been challenged . . .
Reply from author of review
Authors: J. R Absher
Journal: BMJ (1996)

EDITOR,—Jammi N Rao and J D Middleton mention “deficiencies” of my review in Evidence-Based Medicine of the trial of interferon beta-1b. They raise two basic points that deserve a response. Firstly, they caution that my review was not “sufficiently critical of the evidence” and support this claim by noting the “almost diametrically opposite conclusions” reached by me and an anonymous reviewer. Secondly, they criticise “the approach taken by Evidence-Based Medicine” and “warn” readers who rely …
Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials
Authors: Kerry Dwan, Douglas G. Altman, Mike Clarke, Carrol Gamble, Julian P. T. Higgins, Jonathan A. C. Sterne, Paula R. Williamson, Jamie J. Kirkham
Journal: PLoS Medicine (2014)

In a systematic review of cohort studies, Kerry Dwan and colleagues examine the evidence for selective reporting and discrepancies in analyses between journal publications and other documents for clinical trials. Please see later in the article for the Editors' Summary
Newer Oral Anticoagulants Should Be Used as First-Line Agents to Prevent Thromboembolism in Patients With Atrial Fibrillation and Risk Factors for Stroke or Thromboembolism
Authors: Christopher B. Granger, Luciana V. Armaganijan
Journal: Circulation (2012)

T he incidence of atrial fibrillation (AF) appears to be increasing, even after adjustment for aging of the population. 1 One in 4 people is projected to develop AF in his or her lifetime. 2Patients with AF have a 5-fold increased risk of stroke, and it is estimated that 15% to 20% of all strokes are attributable to AF.Moreover, death and disability from stroke complicating AF are particularly high. 3Thus, stroke related to AF is a substantial and growing public health burden.
Rate and rhythm dependency of propagation from normal myocardium to a Ba++, K+-induced slow response zone in rabbit left atrium.
Authors: M O Masuda, A P de Carvalho
Journal: Circulation Research (1982)

Strips of rabbit atrium 2-3 mm wide and 10-12 mm long were used to study how normal propagating action potentials excite a region where slow responses are the only form of electrical activity. One end of the preparation was bathed in normal Tyrode's solution. The rest was exposed to Tyrode's solution with high K+ (12.7 mM) and Ba++ (1 mM) (TKBa solution). The normal end was electrically stimulated and activity was monitored extra- and intracellularly (3 M KCl microelectrodes) as it propagated into the TKBa-treated region. We observed that the slow response could be elicited optimally by the normal action potential only within a limited range of stimulation frequencies (from around 0.3 to 1 Hz). At higher frequencies, progressive "fatigue" of slow response was observed. At frequencies lower than this range, normal action potentials were unable to stimulate slow response. To clarify the mechanism under this behavior, slow responses were directly elicited by electrical stimulation of strips wholly bathed in TKBa. Rate dependency of slow response excitability was again observed. Conclusions are: slow response excitability is enhanced transiently at each stimulation; the enhanced excitability state subsides very slowly and may take as long as 10 seconds to disappear; the enhanced state is cumulative from cycle to cycle so that excitability increases with increasing frequencies of stimulation above 0.1 Hz; and high frequency block due to fatigue and block due to excitability depression at low frequency delimit an optimal frequency window for slow response excitation and conduction.
New Federal Stances on TB Control May Be Confusing to Health Care Facilities
Authors: Rebecca Voelker
Journal: JAMA (1993)

THE NEXT generation of federal guidelines and regulations for controlling the spread of tuberculosis (TB) is on its way. But instead of offering much-needed guidance based on consensus among national experts, the new documents may continue to confuse the issue with potentially conflicting advice based on gaps in scientific data on the transmission of<i>Mycobacterium tuberculosis</i>. Earlier this month, the Centers for Disease Control and Prevention (CDC), Atlanta, Ga, published a draft of long-awaited revisions to its 1990 guidelines on the prevention of TB transmission in health care settings. At the same time, the Occupational Safety and Health Administration (OSHA) has drafted a memorandum clarifying how inspections of health care facilities for occupational TB exposure should be carried out. <h3>Potential for Confusion</h3> Several groups, including the American Medical Association (AMA), were invited to review drafts offered by both federal agencies. In a letter to David Zeigler, the acting assistant secretary
RE-APPRAISAL OF ELECTROCARDIOGRAM INTERPRETATION IN YOUNG ATHLETES: SHOULD AXIS DEVIATION AND VOLTAGE CRITERION FOR ATRIAL ENLARGEMENT BE CATERGORISED AS ABNORMAL IN ATHLETES
Authors: Sabiha Gati, Saqib Ghani, Abbas Zaidi, Nabeel Sheikh, Michael Papadakis, Nicolene Van Nierkerk, Lucia Chen, Matthew Reed, Sanjay Sharma
Journal: Journal of the American College of Cardiology (2012)
Drug Testing Upheld, Decried; Physicians Asked to Help Decide
Authors: Marsha F. Goldsmith
Journal: JAMA (1988)

"EXTRAORDINARY INTRUSION" is the way mass urine screening of employees for drugs of abuse is regarded by John P. Morgan, MD, director of pharmacology, Mount Sinai School of Medicine, City University of New York. "Inappropriate, tarted-up numbers are being cited as if they were scientific data to support policy," he charged. Morgan spoke at the first scientific consensus conference on "Clinical Pharmacologic Implications of Urine Screening for Illicit Substances of Abuse," held recently in San Diego in conjunction with the annual meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT). He represents one side of a controversy that is no closer to being resolved today than it was before the experts assembled to conduct a scientific review of the evidence. The other side is represented with statements such as, "Drug testing prevents drug abuse when it is part of a company's whole drug-control program." That is the opinion