tbuckley/cabot-search huggingface dataset:
Prevalence of Obesity and Trends in Body Mass Index Among US Children and Adolescents, 1999-2010
Authors: Cynthia L Ogden, Margaret D Carroll, Brian K Kit, Katherine M Flegal
Journal: JAMA (2012)

The prevalence of childhood obesity increased in the 1980s and 1990s but there were no significant changes in prevalence between 1999-2000 and 2007-2008 in the United States.To present the most recent estimates of obesity prevalence in US children and adolescents for 2009-2010 and to investigate trends in obesity prevalence and body mass index (BMI) among children and adolescents between 1999-2000 and 2009-2010.Cross-sectional analyses of a representative sample (N = 4111) of the US child and adolescent population (birth through 19 years of age) with measured heights and weights from the National Health and Nutrition Examination Survey 2009-2010.Prevalence of high weight-for-recumbent length (≥95th percentile on the growth charts) among infants and toddlers from birth to 2 years of age and obesity (BMI ≥95th percentile of the BMI-for-age growth charts) among children and adolescents aged 2 through 19 years. Analyses of trends in obesity by sex and race/ethnicity, and analyses of trends in BMI within sex-specific age groups for 6 survey periods (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, and 2009-2010) over 12 years.In 2009-2010, 9.7% (95% CI, 7.6%-12.3%) of infants and toddlers had a high weight-for-recumbent length and 16.9% (95% CI, 15.4%-18.4%) of children and adolescents from 2 through 19 years of age were obese. There was no difference in obesity prevalence among males (P = .62) or females (P = .65) between 2007-2008 and 2009-2010. However, trend analyses over a 12-year period indicated a significant increase in obesity prevalence between 1999-2000 and 2009-2010 in males aged 2 through 19 years (odds ratio, 1.05; 95% CI, 1.01-1.10) but not in females (odds ratio, 1.02; 95% CI, 0.98-1.07) per 2-year survey cycle. There was a significant increase in BMI among adolescent males aged 12 through 19 years (P = .04) but not among any other age group or among females.In 2009-2010, the prevalence of obesity in children and adolescents was 16.9%; this was not changed compared with 2007-2008.
<i>BRCA</i> Germline Mutations in Jewish Patients With Pancreatic Adenocarcinoma
Authors: Cristina R. Ferrone, Douglas A. Levine, Laura H. Tang, Peter J. Allen, William Jarnagin, Murray F. Brennan, Kenneth Offit, Mark E. Robson
Journal: Journal of Clinical Oncology (2008)

Purpose The prognostic significance of germline BRCA1 and BRCA2 mutations in Jewish patients with pancreatic adenocarcinoma (PAC) is unknown. Our objective was to define the prevalence of BRCA1 and BRCA2 in an unselected group of Jewish patients and to compare the clinical characteristics and overall survival (OS) of patients with resected BRCA mutation-associated PAC to PAC patients without mutations. Patients and Methods Jewish patients with PAC resected between January 1986 and January 2004 were identified. DNA was extracted from the archived material, anonymized, and genotyped for founder mutations in BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT). Standard two-sided statistical tests were utilized. Results Of the 187 Jewish patients who underwent resection for PAC, tissue was available for 145 patients. Eight subjects (5.5%) had a BRCA founder mutation (two with BRCA1 [1.3%], six with BRCA2 [4.1%]). The BRCA2 founder mutation was identified in 4.1% of patients with pancreatic adenocarcinoma compared with only 1.1% of cancer-free Washington, DC,–area controls (4.1% v 1.1%; P = .007; odds ratio, 3.85; 95% CI, 2.1 to 10.8). Patients with and without BRCA1 or BRCA2 mutations did not differ in age (mean, 66 v 73 years; P = .6) or other clinicopathologic features. OS was not significantly different (median, 6 v 16 months; P = .35). A previous cancer was reported by 24% (35 of 145) of patients with the most common sites being breast cancer (9 of 35; 74%) and prostate cancer (8 of 35; 23%). Conclusion Founder mutations for BRCA1 and BRCA2 were identified in 5.5% of Ashkenazi patients operated on for PAC. BRCA2 mutations were more prevalent than documented by population studies. Consistent with previous reports, BRCA2 mutations are associated with an increased risk of PAC.
Derailed Estrogen Signaling and Breast Cancer: An Authentic Couple
Authors: Bramanandam Manavathi, Oindrilla Dey, Vijay Narsihma Reddy Gajulapalli, Raghavendra Singh Bhatia, Suresh Bugide, Rakesh Kumar
Journal: Endocrine Reviews (2012)

Estrogen or 17β-estradiol, a steroid hormone, plays a critical role in the development of mammary gland via acting through specific receptors. In particular, estrogen receptor-α (ERα) acts as a transcription factor and/or a signal transducer while participating in the development of mammary gland and breast cancer. Accumulating evidence suggests that the transcriptional activity of ERα is altered by the action of nuclear receptor coregulators and might be responsible, at least in part, for the development of breast cancer. In addition, this process is driven by various posttranslational modifications of ERα, implicating active participation of the upstream receptor modifying enzymes in breast cancer progression. Emerging studies suggest that the biological outcome of breast cancer cells is also influenced by the cross talk between microRNA and ERα signaling, as well as by breast cancer stem cells. Thus, multiple regulatory controls of ERα render mammary epithelium at risk for transformation upon deregulation of normal homeostasis. Given the importance that ERα signaling has in breast cancer development, here we will highlight how the activity of ERα is controlled by various regulators in a spatial and temporal manner, impacting the progression of the disease. We will also discuss the possible therapeutic value of ERα modulators as alternative drug targets to retard the progression of breast cancer.
Documenting the Global Burden of Cardiovascular Disease
Authors: Salim Yusuf, Martin McKee
Journal: Circulation (2014)

Burden of Disease (GBD) was a seminal moment for international health. 1 In a world characterized by what has been termed a "scandal of ignorance," 2 where most peoples' existence was never recorded, the authors undertook the heroic task of estimating not only how many people were dying and from what conditions but also how many were living with disability.By combining these measures to create the disability-adjusted life year, they changed the global health discourse forever.The task was enormous.They had to include all countries, including many that had attracted virtually no attention from health researchers and that lacked vital registration systems.They scoured the world for data, extracting information from dusty archives, and analyzed surveys that had been forgotten. Article see p 1483 and p 1493However, existing data only went so far; alternatives were needed.The authors created complex (although, for some, virtually incomprehensible) models that established relationships in countries with data for variables such as national income and patterns of disease and then extrapolated to countries and regions or for conditions where data were unavailable to fill the many gaps. 3They also developed ambitious methodologic and empiric approaches to understand associations between mortality and the much less well researched disability and to measure the contribution of different disease states to both. 4 These efforts, in turn, have stimulated a massive increase in data collection, with expansions in vital registration systems, sentinel surveillance sites, 5 and methodologic refinements of instruments such as verbal autopsy. 6As a result, the 2010 GBD took our understanding of the health of the world's population to a new level, 7 although, as the accompanying articles in this issue of Circulation demonstrate, there are still many issues to be resolved. 8,9However, the analyses presented raise important issues for policy and action in several areas.First, these articles confirm the success in reducing mortality from cardiovascular disease (CVD) in most rich countries.These are remarkable public health achievements.However, progress in other parts of the world has been slow or nonexistent.
Vertical gradients of lung density in supine subjects with fibrosing alveolitis or pulmonary emphysema.
Authors: A B Millar, D M Denison
Journal: Thorax (1990)

Computed tomography was used to determine the vertical gradient of density in the peripheral lung tissue of 12 patients with histologically proved fibrosing alveolitis and 12 patients with chronic bronchitis and evidence of pulmonary emphysema on the computed tomograms. Measurements were made at total lung capacity and at residual volume and compared with similar measurements from 12 normal subjects reported in a previous study. At residual volume the mean peripheral tissue density in the emphysematous lungs was 0.081 kg/l compared with 0.426 kg/l in the fibrotic lungs and 0.323 kg/l in the normal lungs. The observed densities in the three groups were compared with those in a theoretical model predicting the vertical changes of lung density caused by gravitational effects that would be found in lungs with differing compliance. The emphysematous lungs showed a much greater increase of density with descent down the lung than that predicted for normal lungs, and the results were explicable by an increase in compliance. The fibrotic lungs showed considerably less change in density than expected, implying loss of compliance. It is suggested that local changes of compliance are important determinants of vertical density gradients in diseased lungs.
Vital capacity in lying position: important in Duchenne patients
Authors: P. Wijkstra, A. Hazenberg, J. Nieuwenhuis
Journal: European Respiratory Journal (2010)

continue for several years with different epidemiological features.The selection and number of controls is of utmost importance.In an optimal study, both healthy controls and controls with non-pneumonic respiratory infections matched for age and sex from the same area should be considered.Genetic epidemiology offers the frame of reference for such studies.
Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2014)

Description: Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on vitamin supplementation to prevent cardiovascular disease and cancer. Methods: The USPSTF reviewed the evidence on the efficacy of multivitamin or mineral supplements in the general adult population for the prevention of cardiovascular disease and cancer. Population: This recommendation applies to healthy adults without special nutritional needs (typically aged 50 years or older). It does not apply to children, women who are pregnant or may become pregnant, or persons who are chronically ill or hospitalized or have a known nutritional deficiency. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of multivitamins for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of single- or paired-nutrient supplements (except β-carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF recommends against β-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation)
The Effect of the Rate of Breathing on the Maximum Breathing Capacity Determined with a New Spirometer
Authors: L. Bernstein, J. L. D'Silva, D. Mendel
Journal: Thorax (1952)

Very few quantitative observations have been reported on the effect of rate of breathing on the voluntary maximum breathing capacity (M.B.C.).Proctor and Hardy (1949) found that the M.B.C. was achieved at a rate of 30 respirations per minute (R.P.M.).At higher rates of breathing the ventilatory capacity was diminished.These obser- vations are contrary to the findings of other investigators who regard a fast rate of breathing as essential in producing the largest value for the M.B.C. (Gray and Green, 1945; Baldwin, Cournand, and Richards, 1948).None of these investigators used spirometers which had been tested for recording errors (Bernstein and Mendel, 1951), nor were the observations made at con- trolled rates of breathing.The effect of rate of breathing on the M.B.C. of a group of normal subjects has been investi- gated.This work has been performed on a spirometer which is substantially free from recording error.It has been suggested that to control the rate of breathing impairs the subject's performance, but evidence is provided here to show that there is no sound basis for that opinion.THE DESIGN OF THE SPIROMETER Recently Bernstein and Mendel (1951) showed that a spirometer of the conventional pattern commonly used for the M.B.C. test could give records of breath- ing which were grossly inaccurate.The respiratory rates at which these inaccuracies occurred were deter- mined by the mean depth of immersion of the spirometer bell in its water-jacket, while their extent was determined by the rate, volume, and wave-form of the respiratory air-flow.Because these factors are variable in human experiments, an appropriate correc- tion factor, applicable to every estimation on any one apparatus, cannot be deduced.It was also shown that these inaccuracies were due, at least in part, to the inertia of the moving parts of the spirometer.This caused pressure changes to occur within the bell, and these, at certain respiratory rates, tended to excite Using Two Very Light Pulleys.-These, of small diameter, carried on ball-races, are used in place of one which is large and heavy.It can be shown that the moment of inertia of a disc about its centre of revolution is proportional to the square of the radius.and this change reduces the inertia and also the fric- tional resistance to movement.
Urinary N-Acetyl-β-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure
Authors: Orfeas Liangos, Mary C Perianayagam, Vishal S Vaidya, Won K Han, Ron Wald, Hocine Tighiouart, Robert W MacKinnon, Lijun Li, Vaidyanathapuram S Balakrishnan, Brian J G Pereira, Joseph V Bonventre, Bertrand L Jaber
Journal: Journal of the American Society of Nephrology (2007)

The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-β-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology. Mean Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score was 16, 43% had sepsis, 39% required dialysis, and hospital mortality was 24%. Urinary NAG and KIM-1 increased in tandem with APACHE II and Multiple Organ Failure scores. Compared with patients in the lowest quartile of NAG, the second, third, and fourth quartile groups had 3.0-fold (95% confidence interval [CI] 1.3 to 7.2), 3.7-fold (95% CI 1.6 to 8.8), and 9.1-fold (95% CI 3.7 to 22.7) higher odds, respectively, for dialysis requirement or hospital death (<i>P</i> &lt; 0.001). This association persisted after adjustment for APACHE II, Multiple Organ Failure score, or the combined covariates cirrhosis, sepsis, oliguria, and mechanical ventilation. Compared with patients in the lowest quartile of KIM-1, the second, third, and fourth quartile groups had 1.4-fold (95% CI 0.6 to 3.0), 1.4-fold (95% CI 0.6 to 3.0), and 3.2-fold (95% CI 1.4 to 7.4) higher odds, respectively, for dialysis requirement or hospital death (<i>P</i> = 0.034). NAG or KIM-1 in combination with the covariates cirrhosis, sepsis, oliguria, and mechanical ventilation yielded an area under the receiver operator characteristic curve of 0.78 (95% CI 0.71 to 0.84) in predicting the composite outcome. Urinary markers of kidney injury such as NAG and KIM-1 can predict adverse clinical outcomes in patients with ARF.
Origin of Robustness in Generating Drug-Resistant Malaria Parasites
Authors: Krittikorn Kümpornsin, Charin Modchang, Adina Heinberg, Eric H. Ekland, Piyaporn Jirawatcharadech, Pornpimol Chobson, Nattida Suwanakitti, Sastra Chaotheing, Prapon Wilairat, Kirk W. Deitsch, Sumalee Kamchonwongpaisan, David A. Fidock, Laura A. Kirkman, Yongyuth Yuthavong, Thanat Chookajorn
Journal: Molecular Biology and Evolution (2014)

Biological robustness allows mutations to accumulate while maintaining functional phenotypes. Despite its crucial role in evolutionary processes, the mechanistic details of how robustness originates remain elusive. Using an evolutionary trajectory analysis approach, we demonstrate how robustness evolved in malaria parasites under selective pressure from an antimalarial drug inhibiting the folate synthesis pathway. A series of four nonsynonymous amino acid substitutions at the targeted enzyme, dihydrofolate reductase (DHFR), render the parasites highly resistant to the antifolate drug pyrimethamine. Nevertheless, the stepwise gain of these four dhfr mutations results in tradeoffs between pyrimethamine resistance and parasite fitness. Here, we report the epistatic interaction between dhfr mutations and amplification of the gene encoding the first upstream enzyme in the folate pathway, GTP cyclohydrolase I (GCH1). gch1 amplification confers low level pyrimethamine resistance and would thus be selected for by pyrimethamine treatment. Interestingly, the gch1 amplification can then be co-opted by the parasites because it reduces the cost of acquiring drug-resistant dhfr mutations downstream in the same metabolic pathway. The compensation of compromised fitness by extra GCH1 is an example of how robustness can evolve in a system and thus expand the accessibility of evolutionary trajectories leading toward highly resistant alleles. The evolution of robustness during the gain of drug-resistant mutations has broad implications for both the development of new drugs and molecular surveillance for resistance to existing drugs.
Phase I, Pharmacokinetic, and Pharmacodynamic Study of AMG 479, a Fully Human Monoclonal Antibody to Insulin-Like Growth Factor Receptor 1
Authors: Anthony W. Tolcher, John Sarantopoulos, Amita Patnaik, Kyriakos Papadopoulos, Chia-Chi Lin, Jordi Rodon, Barbara Murphy, Bruce Roth, Ian McCaffery, Kevin S. Gorski, Brianne Kaiser, Min Zhu, Hongjie Deng, Greg Friberg, Igor Puzanov
Journal: Journal of Clinical Oncology (2009)

To determine the maximum-tolerated dose (MTD) and to assess the safety, pharmacokinetics, and evidence of antitumor activity of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1 (IGF-1R).Patients with advanced solid malignancies or non-Hodgkin's lymphoma received escalating doses of AMG 479 intravenously (IV) every 2 weeks (Q2W). Blood samples were assayed to determine pharmacokinetic parameters and IGF-1R occupancy on neutrophils; fluorodeoxyglucose-positron emission tomography scans were used to assess tumor metabolic effects.Fifty-three patients received 312 infusions of AMG 479 Q2W. Overall, the most common grades 1 to 2 toxicities were fatigue, thrombocytopenia, fever, rash, chills, and anorexia. One dose-limiting toxicity (ie, grade 3 thrombocytopenia) occurred in a patient at 20 mg/kg during course 1; grade 3 thrombocytopenia (n = 8) and grade 3 transaminitis elevations (n = 1) also were reported but not in the escalation phase. The maximum-planned dose of 20 mg/kg was safely administered; thus, an MTD was not reached. High levels of neutrophil IGF-1R binding and increases from baseline in serum IGF-1 levels were observed in the 12- and 20-mg/kg cohorts. Tumor responses included one durable complete response (CR) and one unconfirmed partial response (PR) in two patients with Ewing/primitive neuroectodermal tumors and included one PR and one minor response in two patients with neuroendocrine tumors. The patients with Ewing/PNET who had a CR have remained disease free on therapy after 28 months.AMG 479 can be administered safely at 20 mg/kg IV Q2W. The absence of severe toxicities, attainment of serum concentrations associated with high levels of IGF-1R binding on neutrophils, and provocative antitumor activity warrant additional studies of this agent.
Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA: Table 1
Authors: J R Stradling, S E Craig, M Kohler, D Nicoll, L Ayers, A J Nunn, D J Bratton
Journal: Thorax (2014)

The Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular (MOSAIC) trial compared 6 months of CPAP therapy, versus no CPAP, in 391 patients with minimally symptomatic obstructive sleep apnoea (OSA). We now report some exploratory outcomes, markers of systemic inflammation (interleukin 6 (IL-6), IL-10, C reactive protein, tumour necrosis factor). We found no consistent changes (all p values >0.13).ISRCTN 34164388.
Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis
Authors: Andrea Pantoja, Christopher Fitzpatrick, Anna Vassall, Karin Weyer, Katherine Floyd
Journal: European Respiratory Journal (2012)

Xpert MTB/RIF is a rapid test to diagnose tuberculosis (TB) and rifampicin-resistant TB. Cost and affordability will influence its uptake. We assessed the cost, globally and in 36 high-burden countries, of two strategies for diagnosing TB and multidrug-resistant (MDR)-TB: Xpert with follow-on diagnostics, and conventional diagnostics. Costs were compared with funding available for TB care and control, and donor investments in HIV prevention and care. Using Xpert to diagnose MDR-TB would cost US$70-90 million per year globally and be lower cost than conventional diagnostics globally and in all high-burden countries. Diagnosing TB in HIV-positive people using Xpert would also cost US$90-101 million per year and be lower cost than conventional diagnostics globally and in 33 out of 36 high-burden countries. Testing everyone with TB signs and symptoms would cost US$434-468 million per year globally, much more than conventional diagnostics. However, in European countries, Brazil and South Africa, the cost would represent <10% of TB funding. Introducing Xpert to diagnose MDR-TB and to diagnose TB in HIV-positive people is warranted in many countries. Using it to test everyone with TB signs and symptoms is affordable in several middle-income countries, but financial viability in low-income countries requires large increases in TB funding and/or further price reductions.