tbuckley/cabot-search huggingface dataset:
Time to face up to research misconduct
Authors: R. Smith
Journal: BMJ (1996)

Britain and many other countries are failing to respond to evidence of misconduct.

Every country that conducts scientific research experiences research misconduct. I can't support that statement with irrefutable evidence, but other countries that have looked for misconduct have found it.1 2 It would be strange if they did not find misconduct. Why should scientific research be the only human activity immune from crookery. Of the countries that conduct scientific research, only a minority—the United States, Denmark, Norway, Finland, Austria, and Australia—have a coherent system for tackling the problem. Other countries need a system for promoting scientific integrity, providing research into misconduct, and detecting, investigating and punishing misconduct when it does occur. We also need to study research misconduct, horrible as it might be, so that we can better understand its epidemiology.

Research misconduct is back on the British agenda after yet another case last week where the General Medical Council struck off a general practitioner for forging the consent forms of patients entered into a research study sponsored by a drug company (p 798).3 Dr Geoffrey Fairhurst was far from being a marginal member of the profession: he was vice chairman of his local medical ethics committee. Dr Fairhurst was the 16th doctor to be found guilty of serious professional misconduct after referral by the Association of the British Pharmaceutical Industry since the association began actively referring such cases in 1988.4 5 Other than those referred by the Association of the British Pharmaceutical Association, the General Medical Council has found only one other doctor guilty of serious misconduct for research misconduct—Malcolm Pearce, the obstetrician and gynaecologist …
Determinants of ventricular arrhythmias in mildly symptomatic patients with coronary artery disease and influence of inducible left ventricular dysfunction on arrhythmia frequency
Authors: Cynthia M. Tracy, Judith Winkler, Erica Brittain, Martin B. Leon, Stephen E. Epstein, Robert O. Bonow
Journal: Journal of the American College of Cardiology (1987)
MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma
Authors: Tsung-Chieh Shih, Yin-Jing Tien, Chih-Jen Wen, Ta-Sen Yeh, Ming-Chin Yu, Chia-Hao Huang, Yun-Shien Lee, Tzu-Chen Yen, Sen-Yung Hsieh
Journal: Journal of Hepatology (2012)
The Angel of Bethesda
Authors: Lester S. King
Journal: JAMA (1973)

Cotton Mather (1663-1728), who introduced inoculation into the British colony of Boston (1721), was a Puritan minister. Intellectually precocious, he had a strong interest in medicine and read extensively in medical texts, but chose the ministry as his profession. Yet he maintained a lifelong interest in medicine.  Mather never served an apprenticeship but he had read medicine voraciously and widely, and his own medical book, The Angel of Bethesda , shows an extraordinary acquaintance with the medical teachings of his time. He was deeply religious and all his medical concepts had a religious orientation. A personal god and a personal devil, sin and redemption, colored his medical teachings.  His book was written over a long period, finished in 1724, but never published. Only a few subsequent writers had studied the manuscript. Parts of it—about one fifth—were published by Beall and Shryock in their excellent little book, Cotton Mather . Now for the
Hemolytic Syndrome Following the Insertion of a Lucite Ball Valve Prosthesis into the Cardiovascular System
Authors: FREDERICK STOHLMAN, STANLEY J. SARNOFF, ROBERT B. CASE, ARTHUR T. NESS
Journal: Circulation (1956)

Permanent bypass of the aortic valve was accomplished in the dog by placing a lucite conduit containing a Hufnagel valve between the left ventricular apex and thoracic aorta. Red cell destruction was produced by the valve in this position and was accompanied by hemoglobinemia, hemoglobinuria, anemia, reticulocytosis and renal hemosiderosis. Red cell survival, as determined with Cr 51 , was markedly shortened.
Potential Economic Benefits of Lower-Extremity Amputation Prevention Strategies in Diabetes
Authors: Daniel A Ollendorf, James G Kotsanos, William J Wishner, Mark Friedman, Tamara Cooper, Marisa Bittoni, Gerry Oster
Journal: Diabetes Care (1998)

OBJECTIVE To estimate the potential economic benefits of selected strategies from published literature—educational interventions, multidisciplinary clinics, and insurance coverage for therapeutic shoes—to reduce the incidence of lower-extremity amputation among individuals with diabetes. RESEARCH DESIGN AND METHODS We developed a model to estimate the expected incidence and associated costs of lower-extremity amputation in a hypothetical cohort of 10,000 people with diabetes. Prevention strategies were assumed to be targeted at individuals with a history of foot ulcer, and benefits were estimated over a period of 3 years. RESULTS The total potential economic benefits (discounted at 5%) of strategies to reduce amputation risk ranged from $2.0 to $3.0 million ($2,900 to $4,442 per person with a history of foot ulcer) over 3 years. Benefits were highest for educational interventions. Most benefits were found to accrue among individuals aged ≥ 70 years. CONCLUSIONS Strategies to reduce the risk of lower-extremity amputation may generate substantial economic benefits and should be a standard component of routine diabetes care. Benefits may best be achieved through a partnership of government, private payers, health care service providers and producers, and individuals with diabetes.
Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles
Authors: Rong Liu, Denis M. Gilmore, Kimberly Ann V. Zubris, Xiaoyin Xu, Paul J. Catalano, Robert F. Padera, Mark W. Grinstaff, Yolonda L. Colson
Journal: Biomaterials (2012)
Liver Dysfunction After Intestinal Bypass
Authors: Richard Catlin
Journal: JAMA (1976)

To the Editor.—  The article by Dr Ames et al on liver dysfunction (235:1249, 1976) points up a problem in the long-term postoperative follow-up of intestinal bypass patients, which is, at best, poorly understood and often ignored, sometimes with serious consequences. Thus, hepatic failure is considered a serious risk to intestinal bypass for morbid obesity.  There is reason to believe that hepatic steatosis is a consequence of carbohydrate-protein imbalance, not a simple protein deficiency, probably exactly like the changes seen in the early stages of kwashiorkor disease. Simple starvation does not produce these changes. The morbidly obese already have some degree of hepatic steatosis at the time of their bypass, and this, in my experience, is not directly related to the degree of obesity but, I suspect, is related to the ratio of carbohydrate to protein these people have eaten to become so obese and to maintain their obesity. Carbohydrates
A CASE OF BILATERAL TUBERCULOSIS OF THE MIDDLE EAR IN AN INFANT.
Authors: DUNBAR ROY
Journal: JAMA (1904)

Whether the case here reported is one of primary or secondary tuberculosis of the middle ear must be left as an open question, just as it has been done in the few cases of this nature previously reported. In studying the history of this case, however, I feel just as warranted in calling it one of primary as I would one of secondary tuberculosis, chiefly on account of the age of the patient and the early manifestation of the middle ear trouble before any other physical signs of involvement. The statement of Friedrich contains a great deal of truth when he says: "It is difficult, if not impossible, from the clinical point of view, to decide whether one has to deal with primary tuberculosis of the bone with secondary involvement of the tympanic cavity, or with the opposite condition." <h3>Patient.</h3> —Baby C., 6 months old, was brought
Exposure to Diesel Exhaust Particles and Indoor Endotoxin During Early Childhood Increases the Risk for Persistent Wheeze at Age Three
Authors: P RYAN, D BERNSTEIN, L LEVIN, J BURKLE, M VILLAREAL, H KALRA, J LOCKEY, G KHURANAHERSHEY, G LEMASTERS
Journal: Journal of Allergy and Clinical Immunology (2008)
Light boxes can help older people with dementia
Authors: S. Pincock
Journal: BMJ (2003)

Older people with dementia whose syndrome includes agitation or sleep disturbance can benefit from bright light therapy during the dark winter months, British researchers have reported.

Harry Allen and E Jane Byrne led a team from Manchester Royal Infirmary and elsewhere, who conducted a randomised, placebo controlled trial of 47 residents of local nursing homes who had severedementia.

They administered light therapy at 10 000 lux two hours daily for two weeks in the treatment arm and 100 lux in an identical light box as the …
A Male Sterilization Clinic
Authors: P. Jackson, B. Phillips, E. Prosser, H. O. Jones, V. R. Tindall, D. L. Crosby, I. D. Cooke, J. M. McGarry, R. W. Rees
Journal: BMJ (1970)

In the Cardiff Family Planning Association Clinic 330 men have been sterilized during the past 20 months. Selection for operation was made after a detailed discussion between husband, wife, and a Family Planning Association doctor, and with the general practitioner's agreement. The outpatient operation was performed under local anaesthetic by a surgeon. It was regarded as being successful or complete when two semen analyses showed azoospermia at an interval of one month.
Portal-systemic shunts for Budd-Chiari syndrome
Authors: Marshall J. Orloff
Journal: Hepatology (1987)

Nine patients with Budd-Chiari syndrome (BCS) were treated by a portal systemic shunt. One had thrombosis of the superior mesenteric vein (SMV) and another had complete obstruction of the retrohepatic inferior vena cava (IVC). All other patients had a marked stenosis of the retrohepatic IVC with caval pressure ranging from 12 to 24 mmHg (mean: 17 mmHg). Seven patients had an interprosition mesocaval shunt using an autologous jugular vein. The patient with a thrombosed SMV had a portoartial shunt. The patient with an obstructed IVC had a cavoatrial shunt after an erroneous portacaval shunt had failed to relieve ascites. There were no operative deaths and no major postoperative complications. One patient died 19 months after operation of acute leukemia complicating polycythemia rubra vera. All other patients were alive and well 8 months to 6 years after operation. None of them had encephalopathy. These results suggest several comments: (1) Portal systemic shunts are a good treatment for BCS and have a low operative risk. (2) the mesocaval shung is an efficient procedure, even when there is stenosis of the IVC with high caval pressure: shunts to the right atrium should be performed only in the case of complete obstruction or inaccessibility of the IVC. (3) The long-term prognosis is excellent, except in patients with potential malignancies. Therfore, portal systemic shunts should be indicated early in patients with symptomatic BCS.
Dual-Loop Intra-Atrial Reentry in Humans
Authors: Dipen Shah, Pierre Jaïs, Atsushi Takahashi, Meleze Hocini, Jing Tian Peng, Jacques Clementy, Michel Haïssaguerre
Journal: Circulation (2000)

Dual-loop atrial reentrant tachycardias have not been clinically described.Five patients (3 men, 2 women; mean age, 48+/-16 years) were studied 24+/-15 years after surgical closure of an ostium secundum atrial septal defect for drug-resistant atrial tachycardia. Complete tachycardia mapping was performed in the right atrium with multipolar catheters and a 3-dimensional electroanatomic mapping system (Biosense), followed by linear radiofrequency ablation of the narrowest part of each complete loop. Six tachycardias with a typical flutter morphology, a cycle length of 262+/-40 ms, and a superior f-wave axis (-77+/-11 degrees ) were mapped, 4 with a Biosense map including 106+/-32 points. Five figure-8 tachycardias had a counterclockwise loop around the tricuspid valve sharing a common anterior channel with a clockwise loop around the lateral atriotomy scar. One tachycardia was thought to have 2 counterclockwise loops around the same obstacles. Radiofrequency delivery in the cavotricuspid isthmus in each case transformed the tachycardia without any pause in a different morphology tachycardia with an inferior P-wave axis (50+/-42 degrees ) and nearly the same cycle length (272+/-39 ms) but with the periatriotomy loop alone. This arrhythmia required ablation of a second isthmus: between the lower end of the atriotomy and the inferior vena cava in 4 and the superior tricuspid annulus in 1. After a follow-up of 19+/-6 months, there were no recurrences.Figure-8 double-loop tachycardias mimicking the ECG pattern of a common atrial flutter occur in some patients after a surgical atriotomy. Ablation of 1 loop produces a sudden transformation to a new reentrant tachycardia formed of the remaining loop that requires ablation at a second isthmus.
Coping with the aftermath of trauma
Authors: Berthold P R Gersons, Miranda Olff
Journal: BMJ (2005)

NICE recommends psychological therapy for post-traumatic stress disorder 

A dequate survival behaviour is a crucial “gift of nature.” Humans have been fairly successful in reducing the threat to life. Nevertheless, crossing a street or driving a car requires increased alertness in order to survive. Natural disasters such as the recent tsunami and man-made disasters such as war, terrorist attacks, killing, robbing, sexual and physical abuse, and plane crashes show how vulnerable we are. After surviving such an event, people need basics—food, shelter, medical care, and consolation. Nowadays psychological care has been added to this list of basic needs for some people.

Doctors ought to know whether and when psychological help is necessary. The new guideline on managing post-traumatic stress disorder in primary and secondary care from the National Institute for Clinical Excellence (NICE) excellently summarises the experiences of sufferers and carers and provides evidence and advice on interventions for adults and children.1 The guideline gives special attention to “disaster planning”; the needs of ex-military personnel, victims of domestic violence, and refugees and asylum seekers; …
Noninvasive Quantification of Solid Tumor Microstructure Using VERDICT MRI
Authors: Eletheria Panagiotaki, Simon Walker-Samuel, Bernard Siow, S. Peter Johnson, Vineeth Rajkumar, R. Barbara Pedley, Mark F. Lythgoe, Daniel C. Alexander
Journal: Cancer Research (2014)

Abstract There is a need for biomarkers that are useful for noninvasive imaging of tumor pathophysiology and drug efficacy. Through its use of endogenous water, diffusion-weighted MRI (DW-MRI) can be used to probe local tissue architecture and structure. However, most DW-MRI studies of cancer tissues have relied on simplistic mathematical models, such as apparent diffusion coefficient (ADC) or intravoxel incoherent motion (IVIM) models, which produce equivocal results on the relation of the model parameter estimate with the underlying tissue microstructure. Here, we present a novel technique called VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) to quantify and map histologic features of tumors in vivo. VERDICT couples DW-MRI to a mathematical model of tumor tissue to access features such as cell size, vascular volume fraction, intra- and extracellular volume fractions, and pseudo-diffusivity associated with blood flow. To illustrate VERDICT, we used two tumor xenograft models of colorectal cancer with different cellular and vascular phenotypes. Our experiments visualized known differences in the tissue microstructure of each model and the significant decrease in cell volume resulting from administration of the cytotoxic drug gemcitabine, reflecting the apoptotic volume decrease. In contrast, the standard ADC and IVIM models failed to detect either of these differences. Our results illustrate the superior features of VERDICT for cancer imaging, establishing it as a noninvasive method to monitor and stratify treatment responses. Cancer Res; 74(7); 1902–12. ©2014 AACR.
Severe Microcirculatory Abnormalities Elicited by<i>E. coli</i> Hemolysin in the Rabbit Ileum Mucosa
Authors: KONSTANTIN MAYER, BETTINA TEMMESFELD-WOLLBRÜCK, ALEXANDER FRIEDLAND, HORST OLSCHEWSKI, MICHAEL REICH, WERNER SEEGER, AND FRIEDRICH GRIMMINGER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Decreased capillary flow and heterogeneity of microvascular perfusion are hallmarks of septic circulatory disturbances, and the gastrointestinal mucosa is considered to be particularly prone to such abnormalities. We investigated the impact of Escherichia coli hemolysin (HlyA), a medically relevant pore-forming bacterial toxin, on the mucosal microvasculature in a constant-flow blood-perfused rabbit ileum model. Microsensor techniques were employed to assess spatial distribution of mucosal hemoglobin oxygenation and relative mucosal hemoglobin content, as well as mucosal-arterial PCO(2) gap. Administration of low doses of HlyA (0.005 to 0.1 hemolytic units [HU]/ml) into the mesenteric artery provoked a transient vasoconstrictor response. Whereas physiological mucosal oxygenation is homogeneous, severe heterogeneity in capillary blood flow distribution appeared, paralleled by a marked increase in the mucosal-arterial PCO(2) gap. In addition, HlyA provoked a dose-dependent increase in relative hemoglobin concentration (rel Hb(conc)) values and edema formation, suggesting postcapillary vasoconstriction and capillary leakage. The observed changes occurred while fully maintaining mesenteric oxygen delivery. We conclude that low doses of HlyA may elicit severe mucosal microcirculatory disturbances in the rabbit ileum under maintenance of global hemodynamics, reminiscent of septic perfusion abnormalities. Pore-forming bacterial toxins may thus be considered as contributors to splanchnic mucosal damage under conditions of severe infection and sepsis.
Results of 250 consecutive cadaver kidney transplants.
Authors: C L Hall, J R Sansom, M Obeid, J D Blainey, B H Robinson, P Mackintosh, P Dawson-Edwards, A D Barnes
Journal: BMJ (1976)

The results of 250 cadaver kidney transplants performed at this hospital between May 1968 and December 1974 were analysed. A functioning transplant was defined strictly as one that maintained the recipient in good health with a serum creatinine below 442 mumol/1 (5 mg/100 ml) without any need for dialysis. The proportions of kidneys functioning after one, two, and three years were 40-4%, 33-9%, and 31-1% respectively, the corresponding survival rates of patients being 62-6%, 57-4%, and 43-8%. The primary failure rate overall was 21-6%, while the failure rates for first, second, and third transplants were 18-1%, 39-9%, and 66-7% respectively. Half of the primary failures were attributed to the use of cadaver kidneys with abnormal vasculature or long ischaemic times or originating from non-ventilated donors. Of the initially successful transplants 49% were subsequently lost due to rejection (53%) or death of the patient with a functioning transplant (46%), and of the secondary losses 58% occurred within three months of transplantation. HLA matching of donor and recipient for two or more antigens was associated with a significant increase in transplant survival--46% at three years as opposed to 9-5% at three years for kidneys with poorer matches.
Abstract LB-77: Crm1-mediated nucleocytoplasmic transport inhibition perturbs multiple cellular pathways to trigger melanoma cell apoptosis
Authors: Gaurav Pathria, Christine Wagner, Stephan Wagner
Journal: Cancer Research (2012)

Abstract Development of multiple resistance mechanisms in melanomas has necessitated the identification of novel drug targets, which when inhibited could impact multiple cellular pathways thus circumventing potential resistance mechanisms. By performing cDNA-microarray analysis, we identified four key components of the nucleocytoplasmic transport machinery, Chromosome Region Maintenance 1 (Crm1), Ran-GTPase, Ran-GTPase Activating Protein 1 (RanGAP1) and Ran Binding Protein 1 (RanBP1) to be overexpressed in human melanoma metastases. Crm1 inhibition, employing the highly specific Crm1 inhibitor Leptomycin B (LMB) induced a dramatic depletion of pro-survival/cytoplasmic Erk1/2 and p90RSK1 and mediated persistent Erk signaling hyperactivation. Consistently, Crm1 inhibition inflicted extensive apoptosis in melanoma cells while sparing immortalized melanocytes and primary lung fibroblasts. Apoptosis required both the intrinsic and extrinsic apoptotic pathways and was associated with a nuclear entrapment and down-regulation of anti-apoptotic Survivin. Apoptosis was preceded by a G1 cell-cycle arrest and even though Crm1 inhibition mediated dramatic p53 and p21 induction exclusively in wild-type p53 melanoma cells, latter's silencing or inactivation failed to alleviate ensuing apoptosis. Notably, Crm1 inhibition elicited cell line specific, G1 to S progression-retarding changes in the expression of multiple cell-cycle regulatory proteins (Cdk2, Cdk4, p27, p16 and p18) thus potentially explaining p53 dispensability. Based on our results, we propose Crm1 as a potential therapeutic target in human melanoma, whose inhibition initiates a multitude of cell context-dependent molecular events to trigger G1-arrest followed by massive apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-77. doi:1538-7445.AM2012-LB-77
Integrin β3 Blockade With Abciximab and Protection From Myocardial Ischemic Events—Reply
Authors: David L. Fischman
Journal: JAMA (1998)

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Conjoining information from different modules: A comparative perspective
Authors: Giorgio Vallortigara, Valeria Anna Sovrano
Journal: Behavioral and Brain Sciences (2002)

The hypothesis that nonhuman species, lacking verbal language, do not really integrate information from different modules, but use instead information sequentially, appears difficult to put under empirical scrutiny. Evidence is discussed showing that in nonhuman species storing of geometric information occurs spontaneously even when landmark information suffices for spatial reorientation, suggesting simultaneous encoding, if not use, of information from different modules.