tbuckley/cabot-search huggingface dataset:
To give and to give not: The behavioral ecology of human food transfers
Authors: Michael Gurven
Journal: Behavioral and Brain Sciences (2004)

The transfer of food among group members is a ubiquitous feature of small-scale forager and forager-agricultural populations. The uniqueness of pervasive sharing among humans, especially among unrelated individuals, has led researchers to evaluate numerous hypotheses about the adaptive functions and patterns of sharing in different ecologies. This article attempts to organize available cross-cultural evidence pertaining to several contentious evolutionary models: kin selection, reciprocal altruism, tolerated scrounging, and costly signaling. Debates about the relevance of these models focus primarily on the extent to which individuals exert control over the distribution of foods they acquire, and the extent to which donors receive food or other fitness-enhancing benefits in return for shares given away. Each model can explain some of the variance in sharing patterns within groups, and so generalizations that ignore or deny the importance of any one model may be misleading. Careful multivariate analyses and cross-cultural comparisons of food transfer patterns are therefore necessary tools for assessing aspects of the sexual division of labor, human life history evolution, and the evolution of the family. This article also introduces a framework for better understanding variation in sharing behavior across small-scale traditional societies. I discuss the importance of resource ecology and the degree of coordination in acquisition activities as a key feature that influences sharing behavior.
Tegaserod and IBS: a perfect match?
Authors: W Grant Thompson
Journal: Gut (2003)

IBS patients require diagnosis, advice, and a reassuring doctor. For constipated patients who need it, tegaserod is safe and effective.

Until recently, there existed little evidence that any therapy was effective for irritable bowel syndrome (IBS). The quality of clinical trials was poor,1,2 and no systematic review3,4 can redeem faulty data.5 Mindful of this, pharmaceutical companies now employ modern clinical trial principles to test IBS drugs. The latest of these efforts is an Asia-Pacific randomised controlled trial of tegaserod by Kellow et al , described in this issue of Gut 6 [see page 671] .6 To judge how well tegaserod matches the needs of IBS patients we must examine the trial methods, results, and conclusions, and divine what is missing from the reports.

The Asia-Pacific study is similar to Western IBS trials of tegaserod.7,8 These represent substantial improvements in trial methodology. The entered subjects had criteria defined IBS and most had a “non-diarrhoea” bowel habit suitable to the drug’s effects. Recruitment was sufficient to show definitive results, and subjects were double blinded and randomly allocated. A primary global outcome was selected with appropriate secondary measures, and the analysis was “intention to treat”. Primary outcome differences were consistently significant at the pre-decided end point, and over 12 weeks. Tegaserod appears safe (sine qua non for IBS), and post-marketing surveillance should detect unexpected adverse effects.

The Kellow study achieved greater therapeutic gain (absolute benefit increase) than prior tegaserod studies (21% v 11.8%7 and …
Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression.
Authors: E Brogi, G Schatteman, T Wu, E A Kim, L Varticovski, B Keyt, J M Isner
Journal: Journal of Clinical Investigation (1996)

Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), an endothelial cell (EC)-specific mitogen, stimulates angiogenesis in vivo, particularly in ischemic regions. VEGF/VPF expression by cells of hypoxic tissues coincides with expression of its two receptors, KDR and flt-1, by ECs in the same tissues. We investigated whether hypoxia or hypoxia-dependent conditions operate in coordinating this phenomenon. Human umbilical vein and microvascular ECs were exposed to direct hypoxia or to medium conditioned (CM) by myoblasts maintained in hypoxia for 4 d. Control ECs were maintained in normoxia or normoxia-CM. Binding of 125I-VEGF to ECs was then evaluated. Hypoxic treatment of ECs had no effect on 125I-VEGF binding. However, treatment of ECs with hypoxia-CM produced a threefold increase in 125I-VEGF binding, with peak at 24 h (P < 0.001, ANOVA). Scatchard analysis disclosed that increased binding was due to a 13-fold increase in KDR receptors/cell, with no change in KDR affinity (Kd = 260 +/- 51 pM, normoxia-CM versus Kd = 281 +/- 94 pM, hypoxia-CM) and no change in EC number (35.6 +/- 5.9 x 10(3) ECs/cm2, normoxia-CM versus 33.5 +/- 5.5 x 10(3) ECs/cm2, hypoxia-CM). Similar results were obtained using CM from hypoxic smooth muscle cells. KDR upregulation was not prevented by addition to the hypoxia-CM of neutralizing antibodies against VEGF, tumor necrosis factor-alpha, transforming growth factor beta 1 or basic fibroblast growth factor. Similarly, addition of VEGF or lactic acid to the normoxia-CM had no effect on VEGF binding. We conclude that mechanism(s) initiated by hypoxia can induce KDR receptor upregulation in ECs. Hypoxic cells, normal or neoplastic, not only can produce VEGF/VPF, but can also modulate its effects via paracrine induction of VEGF/VPF receptors in ECs.
The Dynamics of Diabetes Among Birth Cohorts in the U.S.
Authors: Ezra I. Fishman, Andrew Stokes, Samuel H. Preston
Journal: Diabetes Care (2014)

OBJECTIVE Using a nationally representative sample of the civilian noninstitutionalized U.S. population, we estimated trends in diabetes prevalence across cohorts born 1910-1989 and provide the first estimates of age-specific diabetes incidence using nationally representative, measured data. RESEARCH DESIGN AND METHODS Data were from 40,130 nonpregnant individuals aged 20-79 years who participated in the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994, and the continuous 1999-2010 NHANES. We defined diabetes as HbA1c ≥6.5% (48 mmol/mol) or taking diabetes medication. We estimated age-specific diabetes prevalence for the 5-year age-groups 20-24 through 75-79 for cohorts born 1910-1919 through 1980-1989 and calendar periods 1988-1994, 1999-2002, 2003-2006, and 2007-2010. We modeled diabetes prevalence as a function of age, calendar year, and birth cohort, and used our cohort model to estimate age-specific diabetes incidence. RESULTS Age-adjusted diabetes prevalence rose by a factor of 4.9 between the birth cohorts of 1910-1919 and 1980-1989. Diabetes prevalence rose with age within each birth cohort. Models based on birth cohorts show a steeper age pattern of diabetes prevalence than those based on calendar years. Diabetes incidence peaks at 55-64 years of age. CONCLUSIONS Diabetes prevalence has risen across cohorts born through the 20th century. Changes across birth cohorts explain the majority of observed increases in prevalence over time. Incidence peaks between 55 and 64 years of age and then declines at older ages.
The role of Fc gamma receptors in the activity of immunomodulatory antibodies for cancer
Authors: Ross Stewart, Scott A Hammond, Michael Oberst, Robert W Wilkinson
Journal: Journal for ImmunoTherapy of Cancer (2014)

Antibodies targeting T-cell inhibitory pathways, such as CTLA-4 and PD-1/PD-L1, are emerging as an important class of cancer therapeutics, and a next generation of immunomodulatory therapies targeting alternative inhibitory (e.g. TIM-3, LAG-3, B7-H4, B7-H3, VISTA, A2aR), as well as co-stimulatory (e.g. CD27, OX40, GITR, CD137), pathways are poised to join them. Most of these immunomodulatory antibodies are of IgG isotypes that have low, or no, binding to the Fc gamma receptors (FcγRs) that trigger cell-mediated cytotoxic effector functions such as antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). These isotypes were selected to minimise the risk of depleting the T cells upon which such antibodies depend for their mechanism of action. However, recent preclinical data highlight a potential role for FcγR engagement in the activity of such antibodies. Here we review the biology of the FcγRs and IgG isotypes in both humans and mice, detail the potential roles that FcγR interactions can play in the activity of monoclonal antibodies in general, and of immunomodulatory antibodies in particular, and discuss how preclinical studies on these interactions might be best interpreted and translated to a human setting.
Predictive Models for Breast Cancer Susceptibility from Multiple Single Nucleotide Polymorphisms
Authors: Jennifer Listgarten, Sambasivarao Damaraju, Brett Poulin, Lillian Cook, Jennifer Dufour, Adrian Driga, John Mackey, David Wishart, Russ Greiner, Brent Zanke
Journal: Clinical Cancer Research (2004)

Abstract Hereditary predisposition and causative environmental exposures have long been recognized in human malignancies. In most instances, cancer cases occur sporadically, suggesting that environmental influences are critical in determining cancer risk. To test the influence of genetic polymorphisms on breast cancer risk, we have measured 98 single nucleotide polymorphisms (SNPs) distributed over 45 genes of potential relevance to breast cancer etiology in 174 patients and have compared these with matched normal controls. Using machine learning techniques such as support vector machines (SVMs), decision trees, and naïve Bayes, we identified a subset of three SNPs as key discriminators between breast cancer and controls. The SVMs performed maximally among predictive models, achieving 69% predictive power in distinguishing between the two groups, compared with a 50% baseline predictive power obtained from the data after repeated random permutation of class labels (individuals with cancer or controls). However, the simpler naïve Bayes model as well as the decision tree model performed quite similarly to the SVM. The three SNP sites most useful in this model were (a) the +4536T/C site of the aldosterone synthase gene CYP11B2 at amino acid residue 386 Val/Ala (T/C) (rs4541); (b) the +4328C/G site of the aryl hydrocarbon hydroxylase CYP1B1 at amino acid residue 293 Leu/Val (C/G) (rs5292); and (c) the +4449C/T site of the transcription factor BCL6 at amino acid 387 Asp/Asp (rs1056932). No single SNP site on its own could achieve more than 60% in predictive accuracy. We have shown that multiple SNP sites from different genes over distant parts of the genome are better at identifying breast cancer patients than any one SNP alone. As high-throughput technology for SNPs improves and as more SNPs are identified, it is likely that much higher predictive accuracy will be achieved and a useful clinical tool developed.
Use of imaging data for predicting clinical outcome
Authors: Karim Khan, Pekka Kannus
Journal: British Journal of Sports Medicine (2000)

Use of imaging data for predicting clinical outcomeEDITOR,-We would like to air three points that arise from the paper Sonographic incidence of tendon microtears in athletes with chronic Achilles tendinosis. 1 Firstly, unfortunately the word "partial" has been omitted from the conclusion (abstract).The conclusion currently reads "There appears to be an association between microtear formation and Achilles tendon rupture".The distinction needs to be made, as the paper's Take home message concludes with the words "There may be a role for ultrasound in identifying athletes at high risk of tendon rupture", and in this case it appears that the authors mean complete tendon rupture.It is important that this ambiguity is clarified.Secondly, although it is well accepted that in many cases tendinosis precedes "spontaneous" tendon rupture, 2 it does not necessarily follow that sonographic abnormality will lead to (complete) tendon rupture.The tissue based pathologies found by Kannus and Jozsa may be more subtle than can be detected by sonography.We feel that, without longitudinal data in a large cohort with an appropriate control group, Gibbon and colleagues are not in a position to draw a conclusion on sonographic screenings of athletes.Thirdly, given the cross sectional study design, the authors should provide caveats emphasising that their theory of tendon remodelling paralleling that of bone is purely speculative.Cross sectional athlete-control comparisons (such as those provided to sustain the argument on tendon remodelling) do not provide evidence of causality-such diVerences can result merely from selection bias.If athlete-control diVerence were causally related, then one could take up basketball in order to grow tall.We emphasise the need for prospectively collected data to predict future outcome.Researchers and clinicians should desist from speculating as to the longitudinal clinical significance of imaging data collected at one point in time only.To our knowledge, there is only one published prospective ultrasonography and clinical correlation study in the tendon literature at present, 3 and it shows rather poor predictive value of ultrasonography in terms of development of symptoms and clinical findings of patellar tendinopathy in female basketball players.Until researchers and reviewers acknowledge the importance of longitudinally collected data for predicting clinical outcome, our imaging field will continue to be mired in a debate based on speculation rather than science.
Overdiagnosis of pulmonary emboli by CT pulmonary angiograms
Authors: Uruj Hoda
Journal: Thorax (2013)

CLUB Overdiagnosis of pulmonary emboli by CT pulmonary angiogramsThe authors of this article suggest that pulmonary emboli (PEs) are being overdiagnosed by high-resolution CT pulmonary angiography (CTPA), which detect small, isolated subsegmental PEs that are not clinically important.Data from the USA show an 80% rise in the incidence of PEs between 1998 and 2006 after CTPA was introduced.Despite the large increase in diagnosis, age-adjusted mortality from PE (deaths in the US population) has changed little: from 12.3 to 11.9 per 100 000.Presently the best evidence for overdiagnosis comes from a trial that randomised 1417 patients with suspected PE to receive either ventilation-perfusion (VQ) scanning or CTPA.Although CTPA detected more emboli than VQ scans (19.2% vs 14.2%), there was no difference in mortality (0.3% vs 0.3%) over three months.The main harms from overdiagnosis are unnecessary treatment with anticoagulation and exposure to contrast and radiation.There has been a substantial increase in complications arising from anticoagulation that parallels the increased incidence of PE.There are limitations to inferring overdiagnosis from epidemiological data and currently it is impossible to say which emboli are not clinically important.At present clinicians should test more selectively and consider that the harms of treating isolated subsegmental PEs may outweigh the benefits.An ongoing prospective cohort study assessing the safety of withholding treatment for stable patients with isolated subsegmental PE may shed further light on this issue.
Circulating and tissue angiotensin systems.
Authors: D J Campbell
Journal: Journal of Clinical Investigation (1987)

Angiotensin has many different actions, most of which relate, either directly or indirectly, to the regulation of blood pressure, fluid, and electrolyte homeostasis (1, 2).In addition to potent vasoconstrictor effects, actions ofangiotensin on vasculature in- clude the stimulation ofprostaglandin release (3), the modulation of angiotensin receptor number (4), and the stimulation of an- giogenesis (5).Angiotensin also has important actions on the central and peripheral nervous systems, the adrenal, kidney, in- testine, and heart (6-1 1).Given these multiple diverse actions of angiotensin, two important questions are (a) which of these actions represent normal physiological events, and (b) whether such actions may assume a pathogenic role.These questions have recently been placed in sharper focus by the clinical ap- plication of inhibitors of the renin-angiotensin system (RAS),' and in particular, the use of converting enzyme inhibitors (CEIs) for the treatment of hypertension.Any attempt to answer these questions requires an accurate concept ofthe RAS.The purpose ofthis review is to discuss new concepts concerning angiotensin production by the circulating RAS, how these relate to angio- tensin production within tissues, and the possible mechanisms by which CEIs lower blood pressure.The study of tissue angio- tensin systems is still at an early stage.In this review I have attempted to synthesize a coherent model of the interaction be- tween the circulating and tissue angiotensin systems, which might assist in the interpretation of new developments in this area. Circulating RASAt the present time, the prevailing view holds that the circulating RAS is primarily an endocrine system designed for the general mediation, through the systemic circulation, of the effects of renin on angiotensin production in plasma (12, 13).This concept can be summarized as follows: renin released by the kidney circulates in plasma, where it cleaves angiotensinogen to generate angiotensin I (Al).On passage through the pulmonary vascu- lature AI is converted to angiotensin II (All), which is conveyed by arterial blood to the peripheral tissues, where it exerts its effects by interaction with specific All receptors.
Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats
Authors: B. Sztrymf, A. Rabiller, H. Nunes, L. Savale, D. Lebrec, A. Le Pape, V. de Montpreville, M. Mazmanian, M. Humbert, P. Hervé
Journal: European Respiratory Journal (2004)

Inhibition of tumour necrosis factor‐α (TNF‐α), levels of which are increased in the blood of cirrhotic rats, prevents hyperdynamic circulatory state, mainly by decreasing the vascular overproduction of nitric oxide. Hepatopulmonary syndrome, which is characterised by intrapulmonary vascular dilatation and increased alveolar to arterial oxygen tension difference ( P A-a,O 2 ), is mainly related to pulmonary overproduction of NO by macrophages accumulated in lung vessels. Since TNF‐α is a potent activator of macrophagic inducible nitric oxide synthase (NOS), the aim of this study was to investigate whether TNF‐α inhibition prevented hepatopulmonary syndrome and hyperdynamic circulatory state in rats with cirrhosis. TNF‐α was inhibited by 5 weeks of pentoxifylline (10 mg·kg body weight −1 ·day −1 ) in rats with cirrhosis induced by common bile duct ligation. Cardiac output, pulmonary and systemic vascular resistance, P A-a,O 2 and cerebral uptake of intravenous technetium‐99m‐labelled albumin macroaggregates (which reflects intrapulmonary vascular dilatation) were similar in sham- and pentoxifylline-treated cirrhotic rats. Blood TNF‐α concentrations and pulmonary intravascular macrophage sequestration, as assessed by morphometric analysis and radioactive colloid uptake, were decreased with pentoxifylline. Pentoxifylline also prevented increases in aorta and lung NOS activities and inducible NOS expression. Thus pentoxifylline prevents development of hyperdynamic circulatory state and hepatopulmonary syndrome, probably by inhibiting the effects of tumour necrosis factor‐α on vascular nitric oxide synthase and intravascular macrophages. These results support an important role for tumour necrosis factor‐α in the genesis of hepatopulmonary syndrome.
Surveillance bronchoscopy in children during the first year after lung transplantation: is it worth it?
Authors: C Benden, O Harpur-Sinclair, A S Ranasinghe, J C Hartley, M J Elliott, P Aurora
Journal: Thorax (2006)

<b>Background:</b> Since January 2002, routine surveillance bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy has been performed in all paediatric recipients of lung and heart–lung transplants at the Great Ormond Street Hospital for Children, London, UK, using a newly revised treatment protocol. <b>Aims:</b> To report the prevalence of rejection and bacterial, viral or fungal pathogens in asymptomatic children and compare this with the prevalence in children with symptoms. <b>Participants:</b> The study population included all paediatric patients undergoing single lung transplantation (SLTx), double lung transplantation (DLTx) or heart–lung transplantation between January 2002 and December 2005. <b>Methods:</b> Surveillance bronchoscopies were performed at 1 week, and 1, 3, 6 and 12 months after transplant. Bronchoscopies were classified according to whether subjects had symptoms, defined as the presence of cough, sputum production, dyspnoea, malaise, decrease in lung function or chest radiograph changes. <b>Results:</b> Results of biopsies and BAL were collected, and procedural complications recorded. 23 lung-transplant operations were performed, 12 DLTx, 10 heart–lung transplants and 1 SLTx (15 female patients). The median (range) age of patients was 14.0 (4.9–17.3) years. 17 patients had cystic fibrosis. 95 surveillance bronchoscopies were performed. Rejection (⩾A2) was diagnosed in 4% of biopsies of asymptomatic recipients, and in 12% of biopsies of recipients with symptoms. Potential pathogens were detected in 29% of asymptomatic patients and in 69% of patients with symptoms. The overall diagnostic yield was 35% for asymptomatic children, and 85% for children with symptoms (p&lt;0.001). The complication rate for bronchoscopies was 3.2%. <b>Conclusions:</b> Many children have silent rejection or subclinical infection in the first year after lung transplantation. Routine surveillance bronchoscopy allows detection and targeted treatment of these complications.
Radiographic assessment of hip osteoarthritis progression: impact of reading procedures for longitudinal studies
Authors: G.-R. Auleley
Journal: Annals of the Rheumatic Diseases (2000)

To compare radiographic reading procedures and evaluate their impact on sample size in hip osteoarthritis (OA) longitudinal studies.Pelvic radiographs performed twice, three years apart, in 104 patients with hip OA were read by a single reader using the Kellgren and Lawrence system, joint space narrowing scale, and joint space width (JSW). Reading procedures were (a) films read as single radiographs, (b) films grouped by patient but read in random order, (c) films grouped by patient and chronologically ordered, all with landmarks for JSW measurements, (d) films read as single radiographs, without landmarks for JSW measurements. JSW was measured at the narrowest point with a 0.1 mm graduated magnifying glass.More Kellgren and Lawrence or joint space narrowing grades were modified respectively with the single (42% and 37%) than with the paired (32% and 23%) or chronologically ordered (34% and 29%) reading procedures. Variability of JSW progression was principally related to mean progression (88.3%) and landmarks (almost 10%). Standardised response means were -0.71 with the paired reading procedure with landmarks, -0.68 with the single reading procedure with landmarks, -0.65 with the single reading procedure without landmarks. With landmarks, 10% more patients would be needed using single than paired reading. Using single reading, 10% more patients would be needed without landmarks than with landmarks.Kellgren and Lawrence grading seems to be influenced by the reading procedure, as is joint space narrowing grading, for assessing hip OA. Paired reading procedure with landmarks for JSW should be recommended in longitudinal studies.
New incentives are needed to boost research data sharing, says expert group
Authors: A. O'Dowd
Journal: BMJ (2014)

Better sharing of clinical research data will happen only if there are more incentives to help boost this area of work, concludes a report from four leading research organisations.1

The report says that although there is much enthusiasm for the benefits of early sharing of large research datasets, the reality is that implementing a good data sharing system in …