tbuckley/cabot-search huggingface dataset:
Moving Toward the Next Paradigm for Cardiovascular Prevention
Authors: Jennifer G. Robinson, Kausik Ray
Journal: Circulation (2016)

G uidelines change based on new evidence and methods.The Adult Treatment Panel guidelines evolved over their 3 iterations and focused on a treat-to-goal approach.Following a rigorous systematic review of randomized trials of cholesterol-lowering drug therapy with cardiovascular outcomes, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guideline moved away from the approach recommended in earlier Adult Treatment Panel guidelines, to a new paradigm (Figure 1) for cholesterol treatment based on the use of statin therapy in 4 statin benefit groups, in which there was a clear net atherosclerotic cardiovascular disease (ASCVD) reduction benefit. 1 For primary prevention, strong evidence from 3 exclusively primary prevention trials supported the initiation of statin therapy in those with ≥7.5% 10-year ASCVD risk, and moderate evidence supported statin therapy for those with 5 to <7.5% 10-year ASCVD risk.However, the guidelines stated that the decision to start statin therapy in these patients and in lowerrisk patients should be deliberated within the context of shared decision making in a Clinician-Patient Discussion, because of the potentially narrower margin of benefit and need to elicit patient preferences.Consideration could also be given to other characteristics that may increase ASCVD risk, including family history of premature ASCVD, elevated coronary artery calcium score, high-sensitivity C-reactive protein ≥2 mg/L, ankle brachial index <0.9, or increased lifetime ASCVD risk, or a low-density lipoprotein (LDL-C) level of ≥160 mg/dL.
18P Epithelial-to-mesenchymal transition (EMT) is required for resistance to anti-folate chemotherapy in lung cancer
Authors: S. Liang, T.M. Marti, P. Dorn, L. Froment, S. Hall, S. Berezowska, G. Kocher, R.A. Schmid, R. Peng
Journal: Journal of Thoracic Oncology (2016)
Soundings: Cocktails with the headmaster
Authors: Kevin Barraclough
Journal: BMJ (2001)

We circled each other warily, clutching our canapes to ward off evil. My wife and I had been summoned to a party at our daughter's new school. We were there to swell the numbers and generally enhance the sense of collective smugness that would tempt other parents into stumping up the fees. We drifted, largely ignored, in a sea of the moneyed middle class. We were, I suppose, semi-interesting flotsam buffeted in the heavy swell of self interest. The parental talk was of scholarships, music exams, and hard nosed attrition in the business of education. The heads of departments eddied uncomfortably, dropping the bland conversational gambits of the hairdresser, while parents and prospective parents eyed them carefully, wondering which of them would be of use.
A Report Card on the Physician Work Force in the United States
Authors: Marc L. Rivo, David A. Kindig
Journal: New England Journal of Medicine (1996)

In a 1992 report,1 the Council on Graduate Medical Education concluded that deficiencies in the physician work force, the medical-education system, and public policy would hinder efforts to provide high-quality and affordable health care for all people in the United States. A surplus of specialists, shortages of minority physicians and generalists, poor geographic distribution of physicians, and inadequate training of physicians in key practice skills were identified as problems. A series of national goals were recommended that, if attained by the year 2000, would result in a physician work force better suited in composition and skills to respond to health . . .
Autophagy Differentially Regulates Distinct Breast Cancer Stem-like Cells in Murine Models via EGFR/Stat3 and Tgfβ/Smad Signaling
Authors: Syn Kok Yeo, Jian Wen, Song Chen, Jun-Lin Guan
Journal: Cancer Research (2016)

Cancer stem-like cells contribute to tumor heterogeneity and have been implicated in disease relapse and drug resistance. Here we show the coexistence of distinct breast cancer stem-like cells (BCSC) as identified by ALDH(+) and CD29(hi)CD61(+) markers, respectively, in murine models of breast cancer. While both BCSC exhibit enhanced tumor-initiating potential, CD29(hi)CD61(+) BCSC displayed increased invasive abilities and higher expression of epithelial-to-mesenchymal transition and mammary stem cell-associated genes, whereas ALDH(+) BCSC were more closely associated with luminal progenitors. Attenuating the autophagy regulator FIP200 diminished the tumor-initiating properties of both ALDH(+) and CD29(hi)CD61(+) BCSC, as achieved by impairing either the Stat3 or TGFβ/Smad pathways, respectively. Furthermore, combining the Stat3 inhibitor Stattic and the Tgfβ-R1 inhibitor LY-2157299 inhibited the formation of both epithelial and mesenchymal BCSC colonies. In vivo, this combination treatment was sufficient to limit tumor growth and reduce BCSC number. Overall, our findings reveal a differential dependence of heterogeneous BCSC populations on divergent signaling pathways, with implications on how to tailor drug combinations to improve therapeutic efficacy. Cancer Res; 76(11); 3397-410. ©2016 AACR.
Evidence for the Secretion of an Osteoclast Stimulating Factor in Myeloma
Authors: Gregory R. Mundy, Lawrence G. Raisz, Robert A. Cooper, Geraldine P. Schechter, Sydney E. Salmon
Journal: New England Journal of Medicine (1974)

In an effort to describe the mechanism of bone erosion in patients with multiple myeloma, supernatant fluids from the short-term cultures of bone marrow aspirated from seven patients with myeloma were examined. Six contained a factor that stimulated osteoclastic bone resorption (calcium release greater than controls) in organ culture. This factor was biologically and chemically similar to osteoclast-activating factor, a mediator produced by phytohemagglutinin-activated normal peripheral blood leukocytes. Cultures of bone-marrow cells obtained from seven other patients with a variety of hematologic disorders did not produce a stimulator of bone resorption. Morphologic examination of autopsy and biopsy samples of bone from 37 patients with myeloma showed osteoclasts on bone-resorbing surfaces adjacent to areas of heavy myeloma-cell infiltration. It is suggested that osteolytic bone lesions and hypercalcemia in myeloma are due to the secretion of a soluble factor by myeloma cells that in turn stimulates osteoclastic activity in adjacent bone. N Engl J Med 291: 1041–1046, 1974)
Are welders more at risk of respiratory infections?
Authors: David Coggon, Keith T Palmer
Journal: Thorax (2016)

Welding of metals generates a complex mix of noxious gases and fumes,1 and has been linked with various respiratory diseases including metal fume fever,2 asthma,3 COPD4 and possibly bronchial carcinoma.1 ,2 In addition, there is now strong and consistent epidemiological evidence that welders are at increased risk of infectious, lobar pneumonia. Originally detected in national analyses of occupational mortality,5 the hazard was confirmed by a large case–control study of men admitted to hospitals in the English West Midlands with community-acquired pneumonia,6 and is supported by findings from more recent epidemiological investigations in the UK7 ,8 and other countries.9–11

The elevation of risk is associated specifically with recent exposure,6 and is not apparent in former welders after normal retirement age,5 ,7 suggesting that it reflects a reversible increase in susceptibility to infection. Moreover, it extends to other occupations such as furnacemen and moulders in foundries, who are exposed to metal fume but not to welding gases.5 ,12 It is demonstrable in men who work with ferrous metals,6 ,12 but the involvement of other metals cannot be ruled out. Resolution of this uncertainty with adequate statistical power is a challenge because lobar pneumonia is uncommon, and relatively few workers are exposed to fume exclusively from …
Pharmacokinetic (PK) analysis of a phase I study of continuous oral treatment with the angiokinase inhibitor BIBF 1120, in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer (NSCLC)
Authors: D. R. Camidge, P. Conkling, J. J. Stephenson, P. M. Glassman, Y. Zhao, R. Kaiser, P. Stopfer
Journal: Journal of Clinical Oncology (2008)

3567 Background: BIBF 1120 is a potent, orally available tyrosine kinase inhibitor (VEGFR 1/2/3, PDGFR α/β and FGFR 1/3) that suppresses tumor growth by angiogenesis inhibition. Recently, the combination of a VEGF inhibitor with standard chemotherapy improved the therapeutic outcome of first line NSCLC patients. Methods: The primary objectives of this Phase I trial were to determine the safety, tolerability, the maximum tolerated dose (MTD) and the PK of BIBF 1120 in combination with paclitaxel and carboplatin in previously untreated NSCLC patients. The BIBF 1120 dose was increased by 50 mg per cohort until the MTD was determined. BIBF 1120 was taken on Days 2–21 with carboplatin (AUC= 6 min·mg/mL) and paclitaxel (200 mg/m2) administered on Day 1 of each 21-day cycle. PK samples were taken on Days 1 and 2 of treatment cycle (TC) 1 and 2. PK parameters were analysed by non-compartmental techniques. Results: Twenty-five patients with stage IIIB/IV NSCLC, performance score 0–1, were enrolled and treated at doses of 50 mg/day (n=3), 100 mg/day (n=3), 150 mg/day (n=3), 200 mg/day (n=13) and 250 mg/day (n=3). The MTD of BIBF 1120 was 200 mg bid. BIBF 1120 steady state was reached after 7 days of bid dosing. No systematic change in trough plasma concentrations or deviation from dose linearity of BIBF 1120 was observed in combination with carboplatin and paclitaxel. PK parameters of carboplatin and paclitaxel are displayed in the table. Conclusions: 200 mg of BIBF 1120 bid in combination with standard doses of carboplatin and paclitaxel is considered the recommended dose for continuous daily treatment for patients with advanced or metastatic NSCLC. There were no clinically relevant changes to the PK parameters of paclitaxel or carboplatin after 20 days administration of 200 mg BIBF 1120 bid, showing that this may be a viable combination in future studies. TC1 (before BIBF 1120 dosing) TC2 (after 20 days of BIBF 1120 dosing) N gMean gCV[%] N gMean gCV[%] Paclitaxel AUC0-∞ ng·h/mL 8 18,800 21.6 7 21,900 27.9 Cmax ng/mL 8 6,020 29.2 8 7,260 25.9 Carboplatin AUC0- ∞ ng·h/mL 6 66,300 21.8 5 78,300 32.9 Cmax ng/mL 6 16,900 19.5 6 18,300 37.1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals Inc. US Oncology Boehringer Ingelheim
Noninstitutional treatment for sex offenders in Florida
Authors: H A Moore, J Zusman, G C Root
Journal: American Journal of Psychiatry (1985)

The authors describe the availability and characteristics of noninstitutional treatment for sex offenders found in a survey of 63 community mental health providers in Florida. The results cover offense categories, referral sources, numbers in treatment, annual case load, and program characteristics. More sex offenders were being treated in the community than in state-operated residential programs, and 21% of the patients currently receiving community treatment were self-referred. The authors recommend that researchers and policy makers direct more attention to community treatment of sex offenders, its efficacy, and training for those delivering the treatment.
Tired surgical trainees
Authors: P. A Millner
Journal: BMJ (2002)

Road traffic injuries are a global public health problemEditor-Road traffic crashes and their sequelae are a scourge in all societies, both developed and developing.Each year over a million people are killed in road traffic collisions worldwide and some 10 million people are injured or disabled by these events, 1 predominantly in low and middle income countries. 2 Despite what is known about road traffic crashes and their health consequences, policymakers worldwide show little awareness of their contribution to the burden of disease; consequently they are neglected in service and policy.At the same time there has been limited funding, particularly in low and middle income countries, for traffic related research 3 even though these injuries drain developing economies of 1-2% of gross domestic product (about $100 bn) each year, or twice the total development aid received worldwide by developing countries. 4 The critical issue is that road traffic injuries can be prevented.Many effective strategies have been identified in developed countries, but since the type of traffic injuries in developing countries differ greatly from those in developed countries, the prevention strategies, technologies, and policies cannot simply be exported.They require specific testing and appropriate modification to ensure their effectiveness in developing societies.The World Health Organization, as the lead coordinating agency for international public health, is guiding a science based programme of activities in the prevention of road traffic injury.In 2001 its department of injuries and violence prevention, together with partners, developed a multidisciplinary five year global strategy for this (www.who.int/violence_injury_prevention/index.html).This strategy takes into consideration competing needs and expectations, and limited resources in many countries, and addresses long term sustainable goals.The Global Forum for Health Research and the WHO are supporting an initiative to promote appropriate research in Africa, Asia, and Latin America (see www. globalforumhealth.org/pages/index.asp).This North-South collaborative effort is embarking on an ambitious research agenda for the prevention of road traffic injuries.Complementarily, another initiative, led by the Harvard Center for Population and Development Studies and cosponsored by the WHO, addresses the problem of health equity and road traffic injuries.An alliance of partners will help 10 developing countries to develop appropriate policies and interventions over five years.Dedicating an issue of the BMJ to road traffic injuries is a welcome step in the acknowledgement of this global public health problem.It is also a call for partners around the world to confront the growing epidemic and save lives.
Intravascular Hemolysis, Thrombocytopenia and Other Hematologic Abnormalities Associated with Severe Toxemia of Pregnancy
Authors: J. A. Pritchard, R. Weisman, O. D. Ratnoff, G. J. Vosburgh
Journal: New England Journal of Medicine (1954)

THE pathogenesis of toxemia of pregnancy is not understood. Recently 3 women in whom eclampsia was associated with intravascular hemolysis, thrombocytopenia and clotting defects were studied. These observations, as well as those reported by others, suggest that such an association may not be rare.1 2 3 4 The significance of these observations in relation to the pathogenesis of the symptoms of at least some patients with toxemia of pregnancy is discussed.Case ReportCase 1. J. K. (U.H. 642–676), a 38-year-old woman (blood Group AB, Rh negative) was admitted to the maternity service on March 18, 1953, when she was 35 weeks pregnant. . . .
Effect of Highly Active Antiretroviral Therapy on Thrombocytopenia in Patients with HIV Infection
Authors: José Alberto Arranz Caso, Cristina Sanchez Mingo, Jaime Garcia Tena
Journal: New England Journal of Medicine (1999)

To the Editor: Thrombocytopenia is a common hematologic disorder in persons infected with the human immunodeficiency virus (HIV).1 Although often asymptomatic, the thrombocytopenia in these patient...
The Use of Heparin-Gelatin-Dextrose in Venous Thrombosis and Pulmonary Embolism
Authors: Chilton Crane
Journal: New England Journal of Medicine (1951)

THE chief obstacles to the wide-scale use of heparin in the treatment of venous thromboembolic disease, are two: the expense of the available commercial heparin preparations and the transiency of action of this drug however injected in the usual aqueous solutions. The short-lived action of heparin has necessitated constant venoclysis or numerous separate injections for its administration and numerous clotting-time determinations for its close regulation. The many workers in this field have appreciated that these obstacles of expense and short-lived action could be circumvented simultaneously if the effect of a single injection of heparin could be made to last over . . .
4P Co-amplifications of PD-L1/PD-L2 genes (9p24.1) and PD-L1 protein expression in NSCLC patients
Authors: S. Clavé, D. Casadevall, L. Pijuan, M. Rodríguez-Rivera, P. García-Moreno, Á. Taus, J. Albanell, B. Espinet, E. Arriola, M. Salido
Journal: Journal of Thoracic Oncology (2016)
Predicting which psychiatric patients are at risk of suicide
Authors: S. Hatcher
Journal: BMJ (1996)

Year of surveyFig 1-Decrease in blood lead concentrations in groups at risk of increased lead uptake from traffic emissions and in control subjects living in areas with- out heavy traffic and in general population, United Kingdom, 1984-96 sure of the general population to lead from traffic emissions would have been intermediate between that of the exposed and control groups.Figure 1 shows that, since 1984-7, blood lead concentra- tions have fallen by a factor of 2.6-3.0 in adults and by a factor of 3.6-5.0 in children.A wide range of measures to reduce lead were implemented in Britain throughout the 1980s- for example, lead solder was removed from tins containing food, lead in paint was controlled, and lead in petrol was reduced.All of these, together with the reduced emissions of lead by vehicles owing to the increased sales of lead free petrol since 1987,' will have contributed to the substantial decline in blood lead concentrations that we observed.
Bone Marrow Microenvironment Affects The Pathogenesis Of Multiple Myeloma Through Downregulation Of Alternative Splicing Factor Fox2 In Myeloma Cells
Authors: Weihua Song, Chaolin Zhang, Yiguo Hu, Maria Gkotzamanidou, Parantu Shah, Weisong Shan, Guang Yang, Samir B. Amin, Yu-Tzu Tai, Yi Li, Adam Sperling, Naim Rashid, Florence Magrangeas, Stephane Minvielle, Hervé Avet-Loiseau, Kenneth C. Anderson, Cheng Li, Nikhil C. Munshi
Journal: Blood (2013)
The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis
Authors: Bernd Hartz, Rebecca Marsh, Kanchan Rao, Jan-Inge Henter, Michael Jordan, Lisa Filipovich, Peter Bader, Rita Beier, Birgit Burkhardt, Roland Meisel, Ansgar Schulz, Beate Winkler, Michael H. Albert, Johann Greil, Gülsün Karasu, Wilhelm Woessmann, Selim Corbacioglu, Bernd Gruhn, Wolfgang Holter, Jörn-Sven Kühl, Peter Lang, Markus G. Seidel, Paul Veys, Alexandra Löfstedt, Sandra Ammann, Stephan Ehl, Gritta Janka, Ingo Müller, Kai Lehmberg
Journal: Blood (2016)
Mode of Inheritance of Decreased C3b Receptors on Erythrocytes of Patients with Systemic Lupus Erythematosus
Authors: James G. Wilson, Winnie W. Wong, Peter H. Schur, Douglas T. Fearon
Journal: New England Journal of Medicine (1982)

The erythrocytes of patients with systemic lupus erythematosus have been shown to have a decreased number of receptors for the major cleavage fragment of the third component of complement (C3b). We studied the basis for this decreased number of C3b receptors by measuring the uptake of anti-C3b-receptor antibody on cells from 113 normal subjects, 38 patients with systemic lupus erythematosus, 14 of their spouses, and 47 of their relatives. The normal subjects had 5014 +/- (mean +/- S.E.M.) receptor sites per cell, but the patients and their relatives had significantly fewer sites--2809 +/- 241 and 3167 +/- 196, respectively (P less than 0.0005). The number of sites in the patients' spouses did not differ from normal (P greater than 0.3). Three phenotypes, indicated by the numbers of receptors, occurred in the normal population; a high phenotype (HH, with 5500 to 8500 sites per cell), an intermediate phenotype (HL, with 3000 to 5499), and a low phenotype (LL, less than 3000). These three phenotypes were present in 34, 54, and 12 percent, respectively, of the normal subjects; in contrast, 5, 42, and 53 per cent of patients had these respective phenotypes. Pedigree analyses indicated that these phenotypes were inherited in an autosomal codominant manner. We conclude that the decreased number of C3b receptors in lupus is inherited, not acquired.
Knowledge of cancer clinical trials in screened populations
Authors: J. H. Walsh, D. Sahasrabudhe
Journal: Journal of Clinical Oncology (2007)

17076 Background/Methods: Previously, we reported results regarding knowledge of cancer clinical trials in men undergoing prostate cancer screening. We administered the same questionnaire to 103 women undergoing screening mammography at a single center. We report results from both studies here. Results: The mammography screening group was racially homogeneous as compared to the prostate cancer screening group. Fewer than 3% of women were nonwhite compared to over 20% of men. Fewer women reported college education, 49% vs. 79%. Half the women were employed compared to a third of the men. On 81% of test questions, participants in the breast cancer screening group chose the correct answer 80% or more of the time. This compared to 71% in the prostate cancer screening group. The mean percent correct answers in the breast group was 91% as compared to 82.4% in the prostate group. Women were significantly more knowledgeable about trial oversight, rationale behind clinical trials, and blinding. Randomization and use of placebo were poorly understood by both groups, with 45% of men and women incorrectly answering a question regarding placebo. Univariate t-tests and multi-way ANOVA analyses suggest that college educated women are significantly more knowledgeable about clinical trials. Race, income, employment status, and marital status did not have a significant effect on women's knowledge. When the breast and prostate data were combined in univariate analysis (see table ), gender, college education and race were found to significantly affect knowledge of clinical trials. These findings maintained significance in multi-way ANOVA analysis. Conclusion: In this hypothesis-generating study, white, female, college educated subjects were more knowledgeable about clinical trials. Importantly, similar knowledge gaps were observed in both studied groups. Targeted interventions to educate patients about the rationale behind clinical trials, randomization, and use of placebo may help increase accrual in clinical trials. [Table: see text] No significant financial relationships to disclose.