tbuckley/cabot-search huggingface dataset:
Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure
Authors: George D. Demetri, Christopher R. Garrett, Patrick Schöffski, Manisha H. Shah, Jaap Verweij, Serge Leyvraz, Herbert I. Hurwitz, Antonio Lopez Pousa, Axel Le Cesne, David Goldstein, Luis Paz-Ares, Jean-Yves Blay, Grant A. McArthur, Qiang (Casey) Xu, Xin Huang, Charles S. Harmon, Vanessa Tassell, Darrel P. Cohen, Paolo G. Casali
Journal: Clinical Cancer Research (2012)

To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes.Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed.In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9 weeks; HR, 0.876; P = 0.306) as expected, given the cross-over design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262-1.134; P = 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome.The cross-over design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following cross-over, there was no statistical difference in OS. RPSFT analysis modeled the absence of cross-over, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events.
The cost of an interrupted response pattern
Authors: Thomas R. Zentall
Journal: Behavioral and Brain Sciences (1995)

Abstract Rachlin proposes that the mechanism underlying self-control involves the cost incurred in changing one's response pattern, but his account explains neither how the response pattern is originally established nor why a change in response pattern entails a cost. I suggest that response patterns occur because they tend to be effective (thus alternatives are more costly) and are maintained because the decision process itself is costly.
Cardiovascular health and disease in children: current status. A Special Writing Group from the Task Force on Children and Youth, American Heart Association.
Authors: J H Moller, K A Taubert, H D Allen, E B Clark, R M Lauer
Journal: Circulation (1994)

More than 600,000 children in the United States have a congenital or acquired cardiac abnormality, and millions more are at risk of developing atherosclerotic disease in adulthood, a risk made particularly evident by the prevalence of cardiovascular risk factors in the young. There are barriers to optimum prevention and treatment of these conditions in children and youth. The AHA's Task Force on Children and Youth has described these barriers and outlined a series of recommendations and strategies to meet the challenges they impose. More research is needed, and research initiatives will be developed at scientific conferences designed to review critical areas of cardiac development and etiology of disease in children. Financial support for such research initiatives must be increased. Educational programs on cardiovascular risk factors will be extended to children and their families. When these programs are coordinated with efforts in the community and in schools, they will reduce the prevalence of cardiovascular risk factors. The task force recommends that various departments and committees of the AHA use their resources for the benefit of children: for example, by developing more research initiatives for funding by the AHA or NHLBI and increasing legislative and regulatory efforts in the areas such as mandatory school health programs and tobacco advertising. It is hoped that in the next decade, through research and educational efforts, many advances in the prevention and treatment of cardiovascular diseases in the young will be realized.
Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder
Authors: Helen Blair Simpson, Edna B. Foa, Michael R. Liebowitz, Jonathan D. Huppert, Shawn Cahill, Michael J. Maher, Carmen P. McLean, James Bender, Sue M. Marcus, Monnica T. Williams, Jamie Weaver, Donna Vermes, Page E. Van Meter, Carolyn I. Rodriguez, Mark Powers, Anthony Pinto, Patricia Imms, Chang-Gyu Hahn, Raphael Campeas
Journal: JAMA Psychiatry (2013)

Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.clinicaltrials.gov Identifier: NCT00389493.
Operational implications of using 2006 World Health Organization growth standards in nutrition programmes: secondary data analysis
Authors: Andrew Seal, Marko Kerac
Journal: BMJ (2007)

<b>Objective</b> To assess the implications of adopting the World Health Organization 2006 growth standards in combination with current diagnostic criteria in emergency and non-emergency child feeding programmes. <b>Design</b> Secondary analysis of data from three standardised nutrition surveys (n=2555) for prevalence of acute malnutrition, using weight for height z score (&lt;−2 and &lt;−3) and percentage of the median (&lt;80% and &lt;70%) cut-offs for moderate and severe acute malnutrition from the National Center for Health Statistics/WHO growth reference (NCHS reference) and the new WHO 2006 growth standards (WHO standards). <b>Setting</b> Refugee camps in Algeria, Kenya, and Bangladesh. <b>Population</b> Children aged 6-59 months. <b>Results</b> Important differences exist in the weight for height cut-offs used for defining acute malnutrition obtained from the WHO standards and NCHS reference data. These vary according to a child9s height and according to whether z score or percentage of the median cut-offs are used. If applied and used according to current practice in nutrition programmes, the WHO standards will result in a higher measured prevalence of severe acute malnutrition during surveys but, paradoxically, a decrease in the admission of children to emergency feeding programmes and earlier discharge of recovering patients. The expected impact on case fatality rates of applying the new standards in conjunction with current diagnostic criteria is unknown. <b>Conclusions</b> A full assessment of the appropriate use of the new WHO standards in the diagnosis of acute malnutrition is urgently needed. This should be completed before the standards are adopted by organisations that run nutrition programmes targeting acute malnutrition.
The mechanism whereby bile acid micelles increase the rate of fatty acid and cholesterol uptake into the intestinal mucosal cell.
Authors: H Westergaard, J M Dietschy
Journal: Journal of Clinical Investigation (1976)

Studies were undertaken to define the mechanism whereby bile acid facilitates fatty acid and cholesterol uptake into the intestinal mucosal cell. Initial studies showed that the rate of uptake (Jd) of several fatty acids and cholesterol was a linear function of the concentration of these molecules in the bulk phase if the concentration of bile acid was kept constant. In contrast, Jd decreased markedly when the concentration of bile acid was increased relative to that of the probe molecule but remained essentially constant when the concentration of both the bile acid and probe molecule was increased in parallel. In other studies Jd for lauric acid measured from solutions containing either 0 or 20 mM taurodeoxycholate and saturated with the fatty acid equaled 79.8+/-5.2 and 120.8+/-9.4 nmol.min(-1).100 mg(-1), respectively: after correction for unstirred layer resistance, however, the former value equaled 113.5+/-7.1 nmol.min(-1).100 mg(-1). Maximum values of Jd for the saturated fatty acids with 12, 16, and 18 carbons equaled 120.8+/-9.4, 24.1+/-3.2, and 13.6+/-1.1 nmol.min(-1).100 mg(-1), respectively. These values essentially equaled those derived by multiplying the maximum solubility times the passive permeability coefficients appropriate for each of these compounds. The theoretical equations were then derived that define the expected behavior of Jd for the various lipids under these different experimental circumstances where the mechanism of absorption was assumed to occur either by uptake of the whole micelle, during interaction of the micelle with an infinite number of sites on the microvillus membrane or through a monomer phase of lipid molecules in equilibrium with the micelle. The experimental results were consistent both qualitatively and quantitatively with the third model indicating that the principle role of the micelle in facilitating lipid absorption is to overcome unstirred layer resistance while the actual process of fatty acid and cholesterol absorption occurs through a monomer phase in equilibrium with the micelle.
Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From G Heusch
Authors: G. Heusch
Journal: Cardiovascular Research (1994)

Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From G Heusch Get access Gerd Heusch Gerd Heusch Department of Pathophysiology, Centre of Internal Medicine, University of Essen. Essen. Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 1108–1110, https://doi.org/10.1093/cvr/28.7.1108b Published: 01 July 1994
Stenting of the Arterial Duct and Banding of the Pulmonary Arteries
Authors: Hakan Akintuerk, Ina Michel-Behnke, Klaus Valeske, Matthias Mueller, Josef Thul, Juergen Bauer, Karl-Juergen Hagel, Joachim Kreuder, Paul Vogt, Dietmar Schranz
Journal: Circulation (2002)

Background — Outcome of patients with hypoplastic left heart (HLH) is mainly influenced by the successful first-step palliation according to the Norwood procedure. An alternative approach is heart transplantation (HTX). The feasibility of ductal stenting in newborns with duct-dependent systemic blood flow and bilateral pulmonary artery banding has been reported. But it remains to be elucidated whether this approach allows a new strategy for patients with HLH. Methods and Results — In patients with various forms of HLH (n=11) and prostaglandin E-1 administration, ductal stenting was performed with balloon expandable Jo stents or Saxx stents. Bilateral pulmonary artery banding was surgically accomplished 1 to 3 days after the transcatheter procedure. Unrestricted blood flow through the interatrial septum was secured by balloon dilatation atrial septotomy, as required. Interventional procedures were performed with no mortality. Stent and ductal patency were achieved for up to 331 days. Two patients underwent HTX, and 8 patients had a palliative 1-stage procedure with reconstruction of the aortic arch and bidirectional cavopulmonary connection at the age of 3.5 to 6 months. There were 2 deaths. One patient with preoperative right heart failure died after the reconstructive surgery, and 1 patient died 4 months after ductal stenting and bilateral banding awaiting HTX. Conclusions — The present study is the first clinical trial showing that stenting the duct followed by bilateral pulmonary artery banding in newborns with HLH allows the combination of neoaortic reconstruction, which is part of first-stage palliation of HLH, with the establishment of a bidirectional cavopulmonary connection. Additionally, it allows the chance for HTX after extended waiting periods.
Physical activity, cardiorespiratory fitness and the incidence of type 2 diabetes in a prospective study of men
Authors: John C Sieverdes, Xuemei Sui, Duck-chul Lee, Timothy S Church, Amanda McClain, Gregory A Hand, Steven N Blair
Journal: British Journal of Sports Medicine (2009)

Objective To assess the independent and joint associations between self-reported physical activity (PA) and objectively measured cardiorespiratory fitness (CRF) from a maximal treadmill exercise test and the development of type 2 diabetes mellitus in a large cohort of men. Methods Participants for the current analysis were 23 444 men aged 20–85 years free of cardiovascular disease (CVD), cancer or diabetes at baseline. Incident diabetes were identified from mail-back surveys. Cox regression analysis was used to estimate hazard ratios (HRs), 95% confidence intervals (CIs) and diabetes incidence rates (per 10 000 man-years) according to exposure categories. Results During an average of 18 years of follow-up, 589 incident cases of diabetes were identified. After adjusting for age, examination year, survey response pattern, body mass index, smoking, drinking, fasting glucose, chronic diseases and family history of CVD or diabetes, the walking/jogging/running (WJR) and sport/fitness groups had a 40% and 28% lower risk of developing diabetes compared with the sedentary men, respectively (both p &lt; 0.05). For CRF, diabetes incidence rates were 31.9, 14.5 and 6.5 for low-, moderate- and high-fitness groups, respectively. After adjustment for the above covariables, moderate and high CRF had a 38% and 63% lower risk of developing diabetes compared with the low CRF group (p trend&lt;0.0001). Conclusion Our findings showed a lower risk of developing diabetes for men who participated in a WJR programme or sport/fitness activity, compared with those who were sedentary. Higher levels of fitness were associated with an inverse gradient of incident diabetes.
Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes.
Authors: J B Weinberg, T J Matthews, B R Cullen, M H Malim
Journal: The Journal of Experimental Medicine (1991)

Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells efficiently. Monocytes that were irradiated to assure no DNA synthesis could also be readily infected with HIV-1BaL. Such infections were associated with the integration of HIV-1BaL DNA into the high molecular weight, chromosomal DNA of monocytes. Thus, normal, nonproliferating monocytes differ from T lymphocytes in that a productive HIV-1 infection can occur independently of cellular DNA synthesis. These results suggest that normal nonproliferating mononuclear phagocytes, which are relatively resistant to the destructive effects of this virus, may serve as persistent and productive reservoirs for HIV-1 in vivo.
Endobronchial ultrasound to assess airway wall thickening: validation<i>in vitro</i>and<i>in vivo</i>
Authors: T.J. Shaw, S.L. Wakely, C.R. Peebles, R.L. Mehta, J.M. Turner, S.J. Wilson, P.H. Howarth
Journal: European Respiratory Journal (2004)

Endobronchial ultrasound (EBUS) allows identification of airway wall structures and could potentially be utilised for in vivo studies of airway thickening in asthma. The present study investigated whether inflation of the fluid-filled balloon sheath over the transducer (necessary to provide sonic coupling with the airway wall) influenced in vitro measurements. In vivo comparability of EBUS with high resolution computed tomography scanning (HRCT), an established method for measuring wall thickness, was determined in control subjects. The airway diameter and wall thickness were studied using EBUS in 24 cartilaginous airways obtained from four sheep, before and after balloon sheath inflation during immersion in saline. To assess EBUS versus HRCT comparability of airway measures in vivo , 12 control subjects underwent imaging of the posterior basal bronchus of the right lower lobe by both techniques. Intra- and interobserver agreement were also assessed. Results with and without the balloon sheath gave comparable measures of airway internal diameter and wall thickness in vitro . Statistical analysis showed agreement between EBUS and HRCT, and intra- and interobserver variability in vivo . The current study concludes that endobronchial ultrasound, which does not present a radiation risk, could be utilised in the in vivo study of cartilaginous airway wall remodelling in respiratory diseases, such as asthma.
Primary Sjogren's syndrome with antibodies to HTLV-I: clinical and laboratory features.
Authors: K Eguchi, N Matsuoka, H Ida, M Nakashima, M Sakai, S Sakito, A Kawakami, K Terada, H Shimada, Y Kawabe
Journal: Annals of the Rheumatic Diseases (1992)

The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was studied in patients with primary Sjögren9s syndrome. Thirteen of 36 serum samples were positive by enzyme linked immunosorbent assay (ELISA) and particle agglutination assay for antibodies to HTLV-I and were confirmed by western blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier state. These patients had a high occurrence of extraglandular manifestations such as uveitis, myopathy, and recurrent high fever compared with patients who did not have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased spontaneous proliferation of peripheral blood mononuclear cells compared with those without the antibodies. The proportions of activated and memory T cells (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers than in non-carriers. The presence of antibodies to HTLV-I in some patients with primary Sjögren9s syndrome suggests that HTLV-I may cause primary Sjögren9s syndrome or its extraglandular manifestations, or both.
Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy
Authors: Shigekazu Fujioka, Yasushi Kitaura, Akira Ukimura, Hirofumi Deguchi, Keishiro Kawamura, Tadashi Isomura, Hisayoshi Suma, Akira Shimizu
Journal: Journal of the American College of Cardiology (2000)
Hypertension-Linked Decrease in the Expression of Brain γ-Adducin
Authors: Hong Yang, Sharon C. Francis, Kathleen Sellers, Mia DeBarros, Chengwen Sun, Colin Sumners, Carlos M. Ferrario, Michael J. Katovich, Andrés F. Muro, Mohan K. Raizada
Journal: Circulation Research (2002)

Gene profiling data coupled with adducin polymorphism studies led us to hypothesize that decreased expression of this cytosolic protein in the brain could be a key event in the central control of hypertension. Thus, our objectives in the present study were to (1) determine which adducin subunit gene demonstrates altered expression in the hypothalamus and brainstem (two cardioregulatory-relevant brain areas) in two genetic strains of hypertensive rats and (2) analyze the role of adducins in neurotransmission at the cellular level. All three adducin subunits (alpha, beta, and gamma) were present in the hypothalamus and brainstem of Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. However, only the gamma-adducin subunit expression was 40% to 60% lower in the SH rat compared with WKY rat. A similar decrease in gamma-adducin expression was observed in the hypothalamus and brainstem of the renin transgenic rat compared with its normotensive control. Losartan treatment of the SH rat failed to normalize gamma-adducin gene expression. A hypertension-linked decrease of gamma-adducin was confirmed by demonstrating a decrease in gamma-adducin expression in hypothalamic/brainstem neuronal cultures from prehypertensive SH rats. Neuronal firing rate was evaluated to analyze the role of this protein in neurotransmission. Perfusion of a gamma-adducin-specific antibody caused a 2-fold increase in the neuronal firing rate, an effect similar to that observed with angiotensin II. Finally, we observed that preincubation of neuronal cultures for 8 hours with 100 nmol/L angiotensin II caused a 60% decrease in endogenous gamma-adducin and was associated with a 2-fold increase in basal firing rate. These observations support our hypothesis that a decrease in gamma-adducin expression in cardioregulatory-relevant brain areas is linked to hypertension possibly by regulating the release of neurotransmitters.