tbuckley/cabot-search huggingface dataset:
Midlife Cardiorespiratory Fitness, Incident Cancer, and Survival After Cancer in Men
Authors: Susan G. Lakoski, Benjamin L. Willis, Carolyn E. Barlow, David Leonard, Ang Gao, Nina B. Radford, Stephen W. Farrell, Pamela S. Douglas, Jarett D. Berry, Laura F. DeFina, Lee W. Jones
Journal: JAMA Oncology (2015)

<h3>Importance</h3> Cardiorespiratory fitness (CRF) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases, but its association with incident cancer or survival following a diagnosis of cancer has received little attention. <h3>Objective</h3> To assess the association between midlife CRF and incident cancer and survival following a cancer diagnosis. <h3>Design, Setting, and Participants</h3> This was a prospective, observational cohort study conducted at a preventive medicine clinic. The study included 13 949 community-dwelling men who had a baseline fitness examination. All men completed a comprehensive medical examination, a cardiovascular risk factor assessment, and incremental treadmill exercise test to evaluate CRF. We used age- and sex-specific distribution of treadmill duration from the overall Cooper Center Longitudinal Study population to define fitness groups as those with low (lowest 20%), moderate (middle 40%), and high (upper 40%) CRF groups. The adjusted multivariable model included age, examination year, body mass index, smoking, total cholesterol level, systolic blood pressure, diabetes mellitus, and fasting glucose level. Cardiorespiratory fitness levels were assessed between 1971 and 2009, and incident lung, prostate, and colorectal cancer using Medicare Parts A and B claims data from 1999 to 2009; the analysis was conducted in 2014. <h3>Main Outcomes and Measures</h3> The main outcomes were (1) incident prostate, lung, and colorectal cancer and (2) all-cause mortality and cause-specific mortality among men who developed cancer at Medicare age (≥65 years). <h3>Results</h3> Compared with men with low CRF, the adjusted hazard ratios (HRs) for incident lung, colorectal, and prostate cancers among men with high CRF were 0.45 (95% CI, 0.29-0.68), 0.56 (95% CI, 0.36-0.87), and 1.22 (95% CI, 1.02-1.46), respectively. Among those diagnosed as having cancer at Medicare age, high CRF in midlife was associated with an adjusted 32% (HR, 0.68; 95% CI, 0.47-0.98) risk reduction in all cancer-related deaths and a 68% reduction in cardiovascular disease mortality following a cancer diagnosis (HR, 0.32; 95% CI, 0.16-0.64) compared with men with low CRF in midlife. <h3>Conclusions and Relevance</h3> There is an inverse association between midlife CRF and incident lung and colorectal cancer but not prostate cancer. High midlife CRF is associated with lower risk of cause-specific mortality in those diagnosed as having cancer at Medicare age.
The Relation Between Body Size and Normalized Small Solute Clearances in Continuous Ambulatory Peritoneal Dialysis
Authors: ANTONIOS H. TZAMALOUKAS, GLEN H. MURATA, BETH PIRAINO, DEEPAK MALHOTRA, JUDITH BERNARDINI, PANDURANGA RAO, DIMITRIOS G. OREOPOULOS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The normalized peritoneal clearances of small solutes depend on the ratio of their concentration in dialysate and plasma ( D/P ) and the drain volume ( Dv ) corrected for some measure of body size such as body water ( V ) or body surface area ( BSA ). The clearance formulas ( D/P ) × ( Dv/V ) and ( D/P ) × ( Dv/BSA ) can be used to examine why large individuals tend to be underdialyzed. Large people have low normalized drain volumes ( Dv/V, Dv/BSA ). It is not known whether size affects the D/P ratios. The purpose of this study was to examine the relationship between normalized peritoneal clearances ( Kt/V urea , C Cr per 1.73 m 2 BSA) and four size indicators (weight, height, V , BSA) in 301 patients on continuous ambulatory peritoneal dialysis (four daily exchanges with 2-L exchange volume) who underwent 613 clearance studies. Highly significant ( P &lt; 0.001) nonlinear relationships were found between Kt/V urea and weight ( r 2 = 0.371), height ( r 2 = 0.289), BSA ( r 2 = 0.436), and V ( r 2 = 0.527); and between C Cr and weight ( r 2 = 0.178), height ( r 2 = 0.115), BSA ( r 2 = 0.199), and V ( r 2 = 0.151). There were also significant negative correlations between the normalized drain volumes ( Dv/V and Dv/BSA ) and all four indicators of body size. Raw (not normalized) peritoneal clearances and drain volumes correlated positively with size. However, D/P urea or D/P creatinine did not vary with any size indicator except for a weak association between D/P creatinine and V ( r = 0.089, P = 0.028). This association was not confirmed when V was used to stratify subjects into quartiles, and group differences for D/P creatinine were tested by one-way ANOVA. This study shows that the exclusive cause of the low normalized peritoneal clearances in large subjects on continuous ambulatory peritoneal dialysis is a low normalized drain volume. No evidence was found to indicate that body size influences the D/P ratio of small solutes. The portion of the variance in normalized clearance explained by size varies by size indicator and solute (urea versus creatinine).
Improving MMR vaccination rates: herd immunity is a realistic goal
Authors: P. Cockman, L. Dawson, R. Mathur, S. Hull
Journal: BMJ (2011)

<b>Problem</b> As measles is a highly infectious disease, the United Kingdom recommendation is for at least 95% of children to receive a first vaccination with the measles, mumps, and rubella (MMR) vaccine before age 2 years and a booster before age 5 years to achieve herd immunity and prevent outbreaks. Reported vaccination rates for England have improved since a low level in 2003-4. Coverage for London is consistently lower than for England, however, and concerns have been expressed that there could be an epidemic of measles in the capital. <b>Design</b> Observational time series study. <b>Setting</b> London Borough of Tower Hamlets. <b>Key measurements for improvement </b>Uptake rates for childhood vaccinations. The key target was to reach 95% coverage for the first MMR vaccine before age 2 years. <b>Strategies for change</b> Financial support for the development of geographically based networks of general practices. Commissioning of care packages, incentivising delivery of high quality integrated care with network level vaccination targets of 95%. Innovative use of information technology to enable robust call and recall processes, active follow-up of defaulters, and increased knowledge about the demography of the children most difficult to reach. <b>Effects of change</b> The development of networks of practices facilitated collaborative working among primary care clinicians and other stakeholders; peer review of achievements; and an element of healthy competition. Uptake improved for all childhood vaccinations, and to herd immunity levels for most. Uptake of the first MMR vaccine before age 2 years rose from 80% in September 2009 to 94% in March 2011. <b>Lessons learnt</b> Achieving herd immunity for childhood vaccinations is an achievable target in an ethnically mixed, socially deprived inner city borough. The ability to identify characteristics of the difficult to reach groups, including significant differences in uptake across different ethnicities, will allow targeted interventions that may further improve overall coverage.
Health of the Public
Authors: Jonathan Showstack
Journal: JAMA (1992)

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both. (JAMA. 1992;267:2497-2502)
HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP)
Authors: Andreas Krueger, Stefanie C. Fas, Marco Giaisi, Marc Bleumink, Anette Merling, Christine Stumpf, Sven Baumann, Denise Holtkotte, Valerie Bosch, Peter H. Krammer, Min Li-Weber
Journal: Blood (2006)
Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study
Authors: Hans-Christoph Diener, Ralph L Sacco, Salim Yusuf, Daniel Cotton, Stephanie Ôunpuu, William A Lawton, Yuko Palesch, Reneé H Martin, Gregory W Albers, Philip Bath, Natan Bornstein, Bernard PL Chan, Sien-Tsong Chen, Luis Cunha, Björn Dahlöf, Jacques De Keyser, Geoffrey A Donnan, Conrado Estol, Philip Gorelick, Vivian Gu, Karin Hermansson, Lutz Hilbrich, Markku Kaste, Chuanzhen Lu, Thomas Machnig, Prem Pais, Robin Roberts, Veronika Skvortsova, Philip Teal, Danilo Toni, Cam VanderMaelen, Thor Voigt, Michael Weber, Byung-Woo Yoon
Journal: The Lancet Neurology (2008)
Engineered H5N1: A Rare Time for Restraint in Science
Authors: Thomas V. Inglesby
Journal: Annals of Internal Medicine (2012)

Two scientific teams have recently engineered the H5N1 virus to make it readily transmissible between ferrets. Given that ferrets are considered the most reliable animal surrogate for human influenza infection, the newly engineered H5N1 strain is probably transmissible between humans as well. The potential consequences of an engineered human-transmissible H5N1 strain are stunning. Although seasonal flu infects as much as 20% of the world's population—more than 1 billion persons—each year, only a small fraction of those with seasonal flu dies, most often the oldest, youngest, and sickest. If the newly engineered strain were to escape the laboratory (either by design or by accident) and spread as widely as seasonal flu with anywhere near the current confirmed H5N1 human case-fatality rate, it could endanger the lives of hundreds of millions of persons. The possible benefits of this work do not justify taking such risks. As clinicians, we have a stake in this issue with our responsibilities for the diagnosis and treatment of influenza. We embrace the principle of free and open exchange of scientific information, but we also believe in the principle of “first, do no harm.” These 2 principles have come into a moment of rare conflict. It seems most reasonable and prudent to request that the involved scientific community and its institutions exercise restraint by restricting dissemination of the experimental results and discontinuing work on the engineered H5N1 strains. If a highly compelling case is made for continued work on this strain despite the risks, the work should be controlled and should merit the greatest scrutiny.
When Are "Positive" Clinical Trials in Oncology Truly Positive?
Authors: Alberto Ocana, Ian F Tannock
Journal: JNCI Journal of the National Cancer Institute (2010)

The approval of a new drug for cancer treatment by the regulatory authorities, such as the United States Food and Drug Administration or European Medicines Agency, is usually based on the positive results of one or more randomized phase III clinical trials comparing the investigational treatment with the standard treatment. A clinical trial is presented as positive if the new drug tested on an experimental group shows a statistically significant difference with the control group (P < .05) in the primary endpoint, which is usually a time-to-event endpoint (overall survival or progression-free survival). Such apparently positive clinical trials disregard whether the final value of the difference in the primary endpoints between the experimental and control groups (δ) meets the criterion that was predefined in the protocol. Currently, the trend is to design large trials that may detect statistically significant, but often trivial, differences in survival endpoints. However, recent appeals have been made in the oncology literature for the design of smaller clinical trials to detect or exclude only larger, clinically important, values of δ. Here, we have evaluated 18 randomized phase III clinical trials that were used for the approval of molecular-targeted anticancer drugs by the United States Food and Drug Administration. Results showed that in some of the articles the magnitude of the reported values of δ were lower than the values predefined in the protocol. We suggest that trials should not be declared positive based only on a statistically significant P value, but should also require detection of a difference in survival outcome that equals or exceeds a clinically important value that is specified in the protocol.
Reduced lung function due to biomass smoke exposure in young adults in rural Nepal
Authors: Om P. Kurmi, Graham S. Devereux, W. Cairns S. Smith, Sean Semple, Markus F.C. Steiner, Padam Simkhada, Kin-Bong Hubert Lam, Jon G. Ayres
Journal: European Respiratory Journal (2012)

This study aimed to assess the effects of biomass smoke exposure on lung function in a Nepalese population, addressing some of the methodological issues seen in previous studies. We carried out a cross-sectional study of adults in a population exposed to biomass smoke and a non-exposed population in Nepal. Questionnaire and lung function data were acquired along with direct measures of indoor and outdoor air quality. Ventilatory function (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC) was significantly reduced in the population using biomass across all age groups compared to the non-biomass-using population, even in the youngest (16–25 yrs) age group (mean FEV 1 (95% CI) 2.65 (2.57–2.73) versus 2.83 (2.74–2.91) L; p=0.004). Airflow obstruction was twice as common among biomass users compared with liquefied petroleum gas users (8.1% versus 3.6%; p&lt;0.001), with similar patterns for males (7.4% versus 3.3%; p=0.022) and females (10.8% versus 3.8%; p&lt;0.001), based on the lower limit of normal. Smoking was a major risk factor for airflow obstruction, but biomass exposure added to the risk. Exposure to biomass smoke is associated with deficits in lung function, an effect that can be detected as early as the late teenage years. Biomass smoke and cigarette smoke have additive adverse effects on airflow obstruction in this setting.
Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection
Authors: Nadine M. Lerret, Ting Li, Jiao-Jing Wang, Hee-Kap Kang, Sheng Wang, Xueqiong Wang, Chunfa Jie, Yashpal S. Kanwar, Michael M. Abecassis, Xunrong Luo, Zheng Zhang
Journal: Journal of the American Society of Nephrology (2015)

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.
Chondrosarcoma of the calcaneum and massive soft tissue calcification in a patient with hereditary and acquired connective tissue diseases.
Authors: I P Wicks, A Fleming
Journal: Annals of the Rheumatic Diseases (1987)

We describe the first case of the coexistence of the hereditary connective tissue disorder multiple exostoses (HME) and an acquired connective tissue disorder manifest by the overlap of dermatomyositis (DM), scleroderma (PSS), high titre speckled pattern antinuclear antibodies, and increased antibodies to double stranded deoxyribonucleic acid (DNA). Furthermore this patient developed chondrosarcoma of the calcaneum (an unusual site for this malignancy) and massive soft tissue calcification (an unusual feature of PSS, adult DM, and systemic lupus erythematosus (SLE)).
Abstract 1321: A novel prevention method against re-obstruction of titanium alloy stent for biliary malignancy using generation of hydroxyl radical under ultrasonic irradiation
Authors: Tomonori Fujimura, Osamu Itano, Sachiko Matsuda, Onishi Tatsuya, Minoru Kitago, Masahiro Shinoda, Shigeyuki kawachi, Minoru Tanabe, Chiaki Ogino, Nobuaki Shimizu, Yuko Kitagawa
Journal: Cancer Research (2012)

Abstract [introduction] Palliative biliary drainage using a metallic stent is performed for biliary obstruction by unresectable biliary carcinoma.The most important problem of biliary stenting therapy is re-obstruction due to tumor ingrowth. The generation of hydroxyl radical was investigated during ultrasonic irradiation and in the presence of TiO2(Shimizu, etal.Ultrason.Sonochem.2008).The metal stent which is used for biliary drainage is made of titanium alloy, and it is thought that it could generate hydroxyl radicals under ultrasonic irradiation in the same way. The object of this study was to establish a novel prevention method of re-obstruction of the stent using generation of hydroxyl radical under ultrasonic irradiation. [method] {in vitro}Nickel titanium alloy was ultrasonically irradiated at frequency of 1MHz for 30 seconds and the amount of generated hydroxyl radical was measured when intensity was changed to 0.1-0.5 W/cm2 by APF method. To evaluate the cytotoxic effect of the generated radicals, trypan blue exclusion assay was used.The number of living cells were counted. {in vivo}A stent re-obstruction model was established.Nude mice(BALB c nu/nu) were given an injection of 1.0×107 of human squamous carcinoma A431 cells on the back.After Seven days, a stent was put in the neighborhood of tumor.The irradiation group(n=3) was given 10 minutes-ultrasonic irradiation of 0.3W /cm2 once a day.The non-irradiation group(n=3) was not irradiated. Tumors with stents were resected on the 14th day. Tumor ingrowth area was measured and histlogical examination of the tumors was performed. [result] {in vitro}The maximum amount of hydroxyl radical generation was measured under ultrasonic irradiation of 0.3W /cm2. The number of living cells with titanium alloy under ultrasonic irradiation(0.3W /cm2 30seconds) was 79% of that without ultrasonic irradiation. {in vivo}On the 14th day, tumor ingrowth to the stent was seen in the non-irradiation group of the stent re-obstruction model.Tumor ingrowth to the stent was clearly inhibited in the irradiation group. [conclusion] Hydroxyl radical was generated from a titanium alloy stent by ultrasonic irradiation and seemed to have therapeutic efficacy. Tumor ingrowth was inhibited, and preventive effect against re-obstruction was suggested. 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 1321. doi:1538-7445.AM2012-1321
SPECIFIC FRACTIONATION OF HUMAN ANTIDEXTRAN ANTIBODIES
Authors: Justus Gelzer, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1964)

Human antidextran of one individual, absorbed specifically on sephadex, was fractionated into two populations of antibody molecules by successive elution with oligosaccharides of the isomaltose series of increasing size. The purified antibody fractions and some whole antidextran sera were found to fix complement with dextrans of molecular weight of 195,000 and above. It could be demonstrated by quantitative microcomplement fixation inhibition assays that the antibody eluted with isomaltotriose had a higher affinity for smaller oligosaccharides relative to isomaltohexaose, indicating a high content of antibody molecules with smaller combining sites, while with the second fraction, eluted with isomaltohexaose, the small haptens were very poor inhibitors and the larger oligosaccharides inhibited readily, presumably due to a higher proportion of molecules with larger combining site size. Assays of similarly prepared fractions, obtained from earlier bleedings of the same individual (1), with inhibition of complement fixation were in good agreement with those obtained by inhibition of precipitation. The two purified antidextran fractions were shown to differ with respect to their complement-fixing capacity. The fraction with molecules with smaller size-combining sites fixed only about half as much complement per unit antibody N as did the fraction containing largely molecules with larger combining sites suggesting that the strength of complement fixation is affected by the strength of the antigen-antibody interaction.
ECK FISTULA LIVER SUBNORMAL IN PRODUCING HEMOGLOBIN AND PLASMA PROTEINS ON DIETS RICH IN LIVER AND IRON
Authors: G. H. Whipple, F. S. Robscheit-Robbins, W. B. Hawkins
Journal: The Journal of Experimental Medicine (1945)

The Eck fistula shunts the portal blood around the liver which receives its blood only by way of the hepatic artery. There are slight gross and histological changes in the Eck fistula liver of the dog. There is evidence at times of some functional abnormalities of the liver due to the Eck fistula but the dog can tolerate this fistula for 1 to 8 years and appear normal. Chloroform is tolerated by the Eck fistula dog, which may take twice a lethal dose for the control dog without evidence of significant liver injury. Acacia given by vein is deposited in the Eck fistula liver and impairs further its functional capacity to contribute to hemoglobin production. The stress of anemia brings out the fact that the anemic Eck fistula animal cannot utilize standard diet factors and iron as efficiently as the anemic non-Eck control dog. The output of new hemoglobin in some instances may drop to one-fourth of normal. When hypoproteinemia alone or combined with anemia is produced in the Eck fistula dog, we observe at times very low production of plasma protein-seven a drop to one-tenth of normal. This interrelation of liver abnormality, liver dysfunction, and lessened plasma protein and hemoglobin production is significant. It is generally accepted that the liver is concerned with the production of several plasma proteins-fibrinogen, prothrombin, and albumin. The experiments above indicate that the liver is concerned directly or indirectly with the production of new hemoglobin. Our belief is that the liver contributes to the fabrication of hemoglobin by means of the mobile plasma proteins which to a large extent derive from the liver.