tbuckley/cabot-search huggingface dataset:
Postinduction Dexamethasone and Individualized Dosing of <i>Escherichia Coli</i> L-Asparaginase Each Improve Outcome of Children and Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a Randomized Study—Dana-Farber Cancer Institute ALL Consortium Protocol 00-01
Authors: Lynda M. Vrooman, Kristen E. Stevenson, Jeffrey G. Supko, Jane O'Brien, Suzanne E. Dahlberg, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Kara M. Kelly, Jeffery L. Kutok, Caroline Laverdière, Steven E. Lipshultz, Bruno Michon, Marshall Schorin, Mary V. Relling, Harvey J. Cohen, Donna S. Neuberg, Stephen E. Sallan, Lewis B. Silverman
Journal: Journal of Clinical Oncology (2013)

We assessed the toxicity and efficacy of dexamethasone and a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL).Patients achieving complete remission (CR) on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 were eligible for random assignment to 1) dexamethasone or prednisone, administered as 5-day pulses, every 3 weeks, and 2) weekly EC-Asnase, administered as a 25,000 IU/m(2) fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m(2), adjusted every 3 weeks based on nadir serum asparaginase activity (NSAA) determinations.Between 2000 and 2004, 492 evaluable patients (ages 1 to 18 years) enrolled; 473 patients (96%) achieved CR. Four hundred eight patients (86%) participated in the corticosteroid randomization and 384 patients (81%) in the EC-Asnase randomization. With 4.9 years of median follow-up, dexamethasone was associated with superior 5-year event-free survival (EFS; 90% v 81% for prednisone; P = .01) but higher rates of infection (P = .03) and, in older children, higher cumulative incidence of osteonecrosis (P = .02) and fracture (P = .06). ID EC-Asnase had superior 5-year EFS (90% v 82% for FD; P = .04), but did not reduce the frequency of asparaginase-related toxicity. Multivariable analysis identified both dexamethasone and ID EC-Asnase as independent predictors of favorable EFS.There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method. Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL.
The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material
Authors: Niall D. Ferguson, Eddy Fan, Luigi Camporota, Massimo Antonelli, Antonio Anzueto, Richard Beale, Laurent Brochard, Roy Brower, Andrés Esteban, Luciano Gattinoni, Andrew Rhodes, Arthur S. Slutsky, Jean-Louis Vincent, Gordon D. Rubenfeld, B. Taylor Thompson, V. Marco Ranieri
Journal: Intensive Care Medicine (2012)
How Do Genomes Create Novel Phenotypes? Insights from the Loss of the Worker Caste in Ant Social Parasites
Authors: Chris R. Smith, Sara Helms Cahan, Carsten Kemena, Seán G. Brady, Wei Yang, Erich Bornberg-Bauer, Ti Eriksson, Juergen Gadau, Martin Helmkampf, Dietrich Gotzek, Misato Okamoto Miyakawa, Andrew V. Suarez, Alexander Mikheyev
Journal: Molecular Biology and Evolution (2015)

A central goal of biology is to uncover the genetic basis for the origin of new phenotypes. A particularly effective approach is to examine the genomic architecture of species that have secondarily lost a phenotype with respect to their close relatives. In the eusocial Hymenoptera, queens and workers have divergent phenotypes that may be produced via either expression of alternative sets of caste-specific genes and pathways or differences in expression patterns of a shared set of multifunctional genes. To distinguish between these two hypotheses, we investigated how secondary loss of the worker phenotype in workerless ant social parasites impacted genome evolution across two independent origins of social parasitism in the ant genera Pogonomyrmex and Vollenhovia. We sequenced the genomes of three social parasites and their most-closely related eusocial host species and compared gene losses in social parasites with gene expression differences between host queens and workers. Virtually all annotated genes were expressed to some degree in both castes of the host, with most shifting in queen-worker bias across developmental stages. As a result, despite >1 My of divergence from the last common ancestor that had workers, the social parasites showed strikingly little evidence of gene loss, damaging mutations, or shifts in selection regime resulting from loss of the worker caste. This suggests that regulatory changes within a multifunctional genome, rather than sequence differences, have played a predominant role in the evolution of social parasitism, and perhaps also in the many gains and losses of phenotypes in the social insects.
Cyclooxygenase-2 Blockade Does Not Impair Endothelial Vasodilator Function in Healthy Volunteers
Authors: Subodh Verma, Satish R. Raj, Lana Shewchuk, Kieren J. Mather, Todd J. Anderson
Journal: Circulation (2001)

Background — From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. Methods and Results — Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, n=18) or naproxen (750 mg/d, n=17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 μg/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 μg/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, P =0.27; rofecoxib, P =0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, P =0.55; rofecoxib, P =0.63). Conclusions — We herein describe, for the first time, the effects of COX-2-selective inhibition on endothelium-dependent vasodilatation in healthy adults. COX-2 blockade, when used at the doses employed therapeutically (which are known to inhibit vascular prostacyclin production) did not result in significant changes in endothelial vasodilator responses in healthy volunteers. The effects of COX-2 inhibitors on vasodilator responses in patients with coronary artery disease remain to be determined.
A comparison of terbutaline inhaled by Turbuhaler® and by a chlorofluorocarbon (CFC) inhaler in children with exercise‐induced asthma
Authors: E. Svenonius, M. Arborelius, R. Wiberg, E. Stahl, M. Svensson
Journal: Allergy (1994)

The present study compared the bronchodilating effect of inhalation from the Turbuhaler (0.5 mg terbutaline x 2) with the effect of inhalation from the chlorofluorocarbon (CFC) inhaler (0.25 mg terbutaline x 4) in children aged 9-17 years with reproducible, exercise-induced asthma (EIA). The treatments were given on two occasions, 5 min apart (terbutaline 0.5 mg + 0.5 mg). The study was performed as a double-blind, double-dummy, and placebo-controlled trial in 12 asthmatic children. The study was conducted on three separate days. The bronchoconstriction was induced by steady running on a treadmill. Forced expiratory volume in 1 s (FEV1.0), vital capacity (VC), and volume of trapped gas (VTG) were measured before and after the exercise test and after treatment. The study showed that the same amount of terbutaline inhaled from the Turbuhaler or from a CFC inhaler is equally effective for reversing EIA, and that the Turbuhaler is possibly more effective for treating spasm in small airways.
Physiological profile of elite Iranian junior Greco-Roman wrestlers
Authors: Farhad Rahmani-Nia
Journal: British Journal of Sports Medicine (2010)

The purpose of this study was to describe the physiological profile of elite Iranian junior Greco-Roman wrestlers. Seventy-one elite wrestlers (aged 19.7±0.8 years), who participated in Iran national training camps were selected for this study periodically. The physiological profile included body weight, maximal oxygen consumption (Bruce protocol), muscular endurance and strength (pull-ups, push-ups, grip strength, bench press, squat and bent-knee sit-ups tests), speed (40 yd running), agility (4 × 9 m running) and body composition (7 sites skinfold). Major results (mean ± SD) are as follow: body weight (kg) 77.4 ± 19.5, flexibility (cm) 40.95 ± 5.25, maximal oxygen consumption (ml/kg/min) 50 ± 4.75, bench press (w/kg) 1.47± 0.18, squat (w/kg) 1.76 ± 0.22, push ups (n) 66.7 ± 8.4, pull ups (n) 31.4 ± 11, grip strength (W/N) 0.89± 0.14, bent-knee sit-ups (n) 67± 6.6, speed (s) 5.1± 0.23, agility (s) 8.9± 0.7 and BF (%) 10.8±4.1. The present study provides baseline physiological data which have been used in the prescription of individual training programmes for these athletes. This information is also available to the coaches and contributes to the strategy for individual matches.
Gradual changes of ECG waveform during and after exercise in normal subjects.
Authors: M L Simoons, P G Hugenholtz
Journal: Circulation (1975)

The directions and magnitudes of time-normalized P, QRS, and ST vectors, and other ECG parameters were analyzed during and after multistage exercise in 56 ostensibly healthy men aged 23 to 62. By selective averaging with a digital computer system a single representative beat was obtained from each stage. Measurements were taken from this beat. During exercise, the interval between the spatial maximum of the P wave and the onset of the QRS complex decreased while the magnitude of the P wave increased. The direction of the P vectors did not change. This pattern corresponds to the electrocardiographic manifestations of predominant right atrial overload. No significant changes in the QRS duration were observed. Also the magnitude and spatial orientation of the maximum QRS vectors remained constant. The interval between the QRS onset and the maximum spatial magnitude of the T wave shortened. The terminal QRS vectors and the ST vectors gradually shifted toward the right, and superiorly. The T magnitude lessened during exercise. In the first minute of the recovery period the P and T magnitudes markedly increased. Afterward all measurements gradually returned to the resting level. Mechanisms which may explain the observed ECG changes during and after exercise are discussed, including changes in the blood conductivity and intracardiac blood volume. Age did not contribute to the variance of the ECG measurements, but a significant reduction of this variance could be otained in some ST-segment measurements by relating them to heart rate with linear regression equations (P less than or equal to 0.05). Therefore it is expected that the sensitivity of the exercise ECG for detection of ischemic heart disease would be increased when heart rate dependent normal limits for ST-segment measurements are used. Different criteria should be employed for the interpretation of the ECG during and after exercise.
Biodistribution of Yttrium-90–Labeled Anti-CD45 Antibody in a Nonhuman Primate Model
Authors: Eneida R. Nemecek, Donald K. Hamlin, Darrell R. Fisher, Kenneth A. Krohn, John M. Pagel, Frederick R. Appelbaum, Oliver W. Press, Dana C. Matthews
Journal: Clinical Cancer Research (2005)

Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 ((90)Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD45 ((131)I-anti-CD45) antibody biodistribution in humans.Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of (90)Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of (90)Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of (90)Y-anti-CD45 antibody was then compared with that previously obtained with (131)I-anti-CD45 antibody in macaques.The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of (90)Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Yttrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with (131)I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively.This study shows that (90)Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the (131)I immunoconjugate in the same animal model.
Maternal Clinical Diagnoses and Hospital Variation in the Risk of Cesarean Delivery: Analyses of a National US Hospital Discharge Database
Authors: Katy B. Kozhimannil, Mariana C. Arcaya, S. V. Subramanian
Journal: PLoS Medicine (2014)

Background Cesarean delivery is the most common inpatient surgery in the United States, where 1.3 million cesarean sections occur annually, and rates vary widely by hospital. Identifying sources of variation in cesarean use is crucial to improving the consistency and quality of obstetric care. We used hospital discharge records to examine the extent to which variability in the likelihood of cesarean section across US hospitals was attributable to individual women's clinical diagnoses. Methods and Findings Using data from the 2009 and 2010 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project—a 20% sample of US hospitals—we analyzed data for 1,475,457 births in 1,373 hospitals. We fitted multilevel logistic regression models (patients nested in hospitals). The outcome was cesarean (versus vaginal) delivery. Covariates included diagnosis of diabetes in pregnancy, hypertension in pregnancy, hemorrhage during pregnancy or placental complications, fetal distress, and fetal disproportion or obstructed labor; maternal age, race/ethnicity, and insurance status; and hospital size and location/teaching status. The cesarean section prevalence was 22.0% (95% confidence interval 22.0% to 22.1%) among women with no prior cesareans. In unadjusted models, the between-hospital variation in the individual risk of primary cesarean section was 0.14 (95% credible interval 0.12 to 0.15). The difference in the probability of having a cesarean delivery between hospitals was 25 percentage points. Hospital variability did not decrease after adjusting for patient diagnoses, socio-demographics, and hospital characteristics (0.16 [95% credible interval 0.14 to 0.18]). A limitation is that these data, while nationally representative, did not contain information on parity or gestational age. Conclusions Variability across hospitals in the individual risk of cesarean section is not decreased by accounting for differences in maternal diagnoses. These findings highlight the need for more comprehensive or linked data including parity and gestational age as well as examination of other factors—such as hospital policies, practices, and culture—in determining cesarean section use. Please see later in the article for the Editors' Summary
Half of latest NHS efficiency savings came from staff pay freeze
Authors: A. O'Dowd
Journal: BMJ (2012)

Half of the latest £5.8bn (€7.1bn; $9.3bn) in efficiency savings made by the NHS in 2011-12 was the result of staff’s pay being frozen, MPs have heard.

More deep rooted transformational change in how the NHS operates and focuses its priorities has played only a small part in savings made so far, witnesses told MPs on the parliamentary select committee on health.

The committee, holding its first evidence session on 23 October as part of its inquiry into public expenditure, asked witnesses from the bodies that represent NHS and local government organisations how efficiency savings were being achieved, given that the NHS is expected …
Decreased Serum Concentrations of 25-Hydroxycholecalciferol Are Associated With Increased Risk of Progression to Impaired Fasting Glucose and Diabetes
Authors: Anat Tsur, Becca S. Feldman, Ilan Feldhammer, Moshe B. Hoshen, Gil Leibowitz, Ran D. Balicer
Journal: Diabetes Care (2013)

To study the association between vitamin D status and the risk of incident impaired fasting glucose (IFG) and diabetes in a population-based cohort of diabetes-free subjects.In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40-70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1-37.5, 37.6-50, 50.1-75, and >75 nmol/L.The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03-1.24), 1.77 (1.11-2.83), and 1.43 (1.16-1.76), respectively].Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.
The Evolution of the Epidemic of Charcoal-Burning Suicide in Taiwan: A Spatial and Temporal Analysis
Authors: Shu-Sen Chang, David Gunnell, Benedict W. Wheeler, Paul Yip, Jonathan A. C. Sterne
Journal: PLoS Medicine (2010)

An epidemic of carbon monoxide poisoning suicide by burning barbecue charcoal has occurred in East Asia in the last decade. We investigated the spatial and temporal evolution of the epidemic to assess its impact on the epidemiology of suicide in Taiwan.Age-standardised rates of suicide and undetermined death by charcoal burning were mapped across townships (median population aged 15 y or over = 27,000) in Taiwan for the periods 1999-2001, 2002-2004, and 2005-2007. Smoothed standardised mortality ratios of charcoal-burning and non-charcoal-burning suicide and undetermined death across townships were estimated using Bayesian hierarchical models. Trends in overall and method-specific rates were compared between urban and rural areas for the period 1991-2007. The epidemic of charcoal-burning suicide in Taiwan emerged more prominently in urban than rural areas, without a single point of origin, and rates of charcoal-burning suicide remained highest in the metropolitan regions throughout the epidemic. The rural excess in overall suicide rates prior to 1998 diminished as rates of charcoal-burning suicide increased to a greater extent in urban than rural areas.The charcoal-burning epidemic has altered the geography of suicide in Taiwan. The observed pattern and its changes in the past decade suggest that widespread media coverage of this suicide method and easy access to barbecue charcoal may have contributed to the epidemic. Prevention strategies targeted at these factors, such as introducing and enforcing guidelines on media reporting and restricting access to charcoal, may help tackle the increase of charcoal-burning suicides. Please see later in the article for the Editors' Summary.
Referral criteria for open access gastroscopy: do they inevitably delay the diagnosis of cancer?
Authors: J. W. Berrill, J. Turner, J. Hurley, J. Swift, S. Dolwani, J. T. Green
Journal: Gut (2011)

<h3>Introduction</h3> The All Wales guidelines for management of dyspepsia (2004) advises urgent endoscopy for those patients who have ‘alarm features’, and routine investigation in patients aged over 55 years with unexplained and persistent dyspepsia of recent onset. However there is concern that strict adherence to this guideline may lead to a delay in diagnosis, with early curable cancers not being discovered until alarm features develop and progression to an advanced stage has occurred. The aim of this study is to evaluate the timescale of symptoms in upper gastrointestinal (GI) cancer – to determine if patients experience dyspepsia prior to developing their ‘alarm features’, and hence whether the current guidelines delay diagnosis. <h3>Methods</h3> This prospective study included patients diagnosed with upper GI cancer at endoscopy between May 2004 and January 2007. They were questioned directly after the procedure about the nature and duration of their presenting symptoms, and the number of primary care reviews prior to referral. Patient outcome data has been collected until September 2010. <h3>Results</h3> 60 patients diagnosed with upper GI cancer were included. There were 43 males and 17 females; mean age was 77 years (range 44-92); 36 had oesophageal cancers and 24 gastric cancers; median survival was 284 days (range 8-1998). At referral to endoscopy 56 patients had alarm features, 1 patient had dyspepsia alone, 1 patient presented with chest pain, and 2 patients whose endoscopy referrals were due to incidental findings on CT scans had no upper GI symptoms or alarm features. Of the 56 patients with alarm features 17 reported co-existing dyspepsia; in 3 of these the dyspepsia had been present for many years and clearly pre-dated the cancer, in 4 cases dyspepsia had shortly preceded the alarm feature – the maximum preceding duration being only 8 weeks, and in 10 patients the dyspepsia started at the same time or after development of an alarm feature. None of the 5 patients who were younger than 55 years old complained of dyspepsia. Overall, 20 patients had more than one primary care review prior to their referral for endoscopy. When this group was compared to the 38 patients who were referred at their first primary care review, there was a significant delay in referral (p&lt;0.001) but there was no significant difference in tumour stage at diagnosis (p=0.771) or length of survival (p=0.120). <h3>Conclusion</h3> Patients with upper GI cancer who are referred to endoscopy with alarm features rarely report a significant period of preceding dyspepsia that would have allowed earlier diagnosis. Early upper GI cancer is largely asymptomatic and population screening is the only reliable method to detect these cases. The data from this study supports the use of current guidelines to investigate dyspepsia.