tbuckley/cabot-search huggingface dataset:
Cost-benefit analysis underlies training decisions in elite sport
Authors: Heath T Gabbett, Johann Windt, Tim J Gabbett
Journal: British Journal of Sports Medicine (2016)

Cost-benefit analysis is a term often heard in the world of economics. Businesses seek to maximise profits by comparing the costs and benefits of a proposed venture. Cost-benefit analysis is a valuable analytical technique that can also inform decisions in the clinical sports medicine setting.1 Specifically, cost-benefit analysis provides a useful framework to quantify the relationship between the ‘benefit’ of improved performance from a given training load, and the associated ‘cost’ of increased injury risk.

Elite sport provides a starting point for any discussion relating to the costs and benefits of high workloads. Elite players are often exposed to year-long training and high match frequencies, with periods of a congested calendar, which sometimes increases injury risk.2–4 These competitive demands place physical stress on players, requiring well-developed physical qualities to avoid injury and illness, and to perform optimally. While proposing an economic analysis for evaluating costs and benefits in sports medicine may sound surprising, it is a process managers …
63P Molecular bases for combinatorial treatment strategies in KRAS mutant (KRASm) lung adenocarcinoma (LAC)
Authors: C. Lazzari, N. Karachaliou, A. Verlicchi, I. Chaib, S. Marin, A. Gkountakos, S. Pilotto, J.L. Ramírez Serrano, F. de Marinis, R. Rosell
Journal: Journal of Thoracic Oncology (2016)
Recurrence pattern after concomitant radio-chemotherapy in newly diagnosed glioblastoma patients: Correlation with <i>MGMT</i> promoter methylation status
Authors: A. Tosoni, E. Franceschi, V. Blatt, F. Ruggeri, F. Benevento, S. Bartolini, L. Morandi, L. Scopece, V. Mazzocchi, A. A. Brandes
Journal: Journal of Clinical Oncology (2008)

2027 Background: Temozolomide (TMZ), concomitant with and adjuvant to radiotherapy (RT), has become the standard treatment for newly diagnosed glioblastoma (GBM). The aim of the present analysis was to evaluate the recurrence pattern in GBM patients (pts) treated with this treatment and to assess its correlation with MGMT promoter methylation status. Methods: A review was made of brain MRI images available in 95 GBM pts enrolled from January 2005 to January 2007, all of whom had been prospectively treated with TMZ (75 mg/m2/day) concomitant with standard RT (60 Gy/30F), followed by adjuvant TMZ (150–200 mg/m2 days 1–5, q28, maximum 12 cycles if MRI findings were negative or until progression if MRI appeared positive. An analysis was made of the correlation between MGMT promoter methylation status (assessed with methylation specific PCR) and the recurrence pattern. Results: After a median follow-up of 18 months (range: 6.6 - 44.8), 79 pts (83%) presented GBM recurrence: 57 pts (72%) had recurrence within, and 17 pts (22%) exclusively outside, the RT field; 5 pts (6%) had recurrence both within and outside the field. The median progression free survival (PFS) of pts with recurrence within, within plus outside, and only outside the RT field was 9.2, 8.7, and 14.9 months, respectively (in+in&out vs out p=0.025). The median survival time (MST) was 17.3 months (95%CI: 15.1–20), 14.8 months (95%CI: 10.8-NA), and 26.1 months (95%CI: 19-NA) in pts with recurrence within, within and outside, and only outside the RT field respectively (in+in&out vs out: p=0.013). Recurrence outside the RT field was reported in 15% of unmethylated pts and 42% of methylated pts (p=0.01). About 20% of GBM pts treated with TMZ concomitant and adjuvant to RT may develop recurrence outside the RT field. In pts with methylated MGMT promoter status with a longer PFS and OS, the incidence of recurrence outside the RT field is significantly higher. Conclusions: These data, of value in the development of surveillance strategies for GBM patients, may be an useful aid in selecting treatment for GBM pts in clinical trials. No significant financial relationships to disclose.
GENO-21BRCA1 PROTEIN EXPRESSION PREDICTS SURVIVAL IN GLIOBLASTOMA PATIENTS FROM A NRG ONCOLOGY/RTOG COHORT
Authors: Maria Vassilakopoulou, Minhee Won, Walter Curran, Luis Souhami, Michael Prados, Corey Langer, David Rimm, Jason Hanna, Veronique Neumeister, William Smart, Aidnag Diaz, James Atkins, Lydia Komarnicky, Christopher Schultz, Steven Howard, Adam Dicker, Jonathan Knisely
Journal: Neuro-Oncology (2015)

BACKGROUND: Glioblastoma multiforme is the most common malignant brain tumor, associated with mean survival <1 year in the pre-temozolomide era. Histologic parameters have had limited value in predicting survival among patients with glioblastoma. Despite advances in recent molecular and genetic profiling studies identifying several prognostic and predictive biomarkers, none has translated into routine clinical use. Our aim was to investigate the expression and prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray. METHODS: A tissue array composed of archived glioblastoma tumors from 66 patients treated with surgery, radiation, and non-temozolomide chemotherapy, was provided by the RTOG. RAD51, BRCA-1, PTEN, and miRNA-210 expression levels were assessed using quantitative in-situ hybridization and automated quantitative protein analysis (AQUA). The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Among the four biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with median survival times of 18.9 vs. 4.8 months. CONCLUSIONS: BRCA1 protein expression was an important prognostic determinant in our cohort of glioblastoma patients treated with surgery followed by chemo-radio-therapy. This result may imply that low BRCA1 in the tumor, and the consequent low level of DNA repair, causes vulnerability of the cancer cells to treatment. Prospective validation of these results is necessary. This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 (CCOP) from the National Cancer Institute (NCI) and Genentech.
Hub colonization of central line catheters in children with cancer
Authors: R. Norville, B. Horvath, D. Lee, A. Hyde, M. Gregurich, J. Hilburn, J. Starke, J. Versalovic, B. Mueller, M. Hockenberry
Journal: Journal of Clinical Oncology (2006)

18530 Background: Central venous catheter (CVC) hub sites provide bacterial access to the blood stream through migration along the external and internal surfaces of the catheter. Hub colonization rates vary from 29–38% in the adult literature. While pediatric studies were not found, one study reported the incidence of blood stream infections in neonates to be 30 times higher in catheters with hub colonization compared to catheter hubs that were not colonized. The purpose of this descriptive study was to obtain baseline cultures of CVC hubs to determine the incidence of colonization. Methods: Fifty-one catheter hub cultures were obtained from a convenience sample of 27 children with cancer. The mean age of the patients was 8.2 years (range 0.5–16.2 years); 77% were diagnosed with leukemia and 23% with solid tumors. Cultures were obtained by swabbing the threaded area of the catheter hub after removing the injection cap. A semi-quantitative culture for bacteria and fungus was obtained using standard laboratory procedures by a microbiologist. This study was conducted in a large urban hospital in the Southwest. Results: Fifty-seven percent of the hubs were culture positive. Of those positive cultures, 69%, 24%, 10% and 7% were colonized with 2, 3, 4 and 5 organisms, respectively. The most common organism cultured was coagulase negative staphylococcus. The only significant risk factor for this population was previous central venous catheter infections (p = 0.025). Sixty-nine percent of the lines were tunneled catheters. Central venous catheters were in place on an average of 75.3 days but this was not a factor in the colonization rate. Conclusions: The majority (57%) of the 51 central venous catheter hubs cultured were colonized with at least one organism. This study is the first to evaluate the rate of central venous catheter hub colonization in children with cancer. These findings support the need for more stringent guidelines for central venous catheter care. Further research evaluating the relationship between hub colonization and subsequent blood stream infection is needed. No significant financial relationships to disclose.
Case 13-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Homayoun Kazemi, Albert R. Keller
Journal: New England Journal of Medicine (1971)

Presentation of CaseAn 85-year-old woman was admitted to the hospital because of a chill.Except for diabetes mellitus of the maturity-onset type, for which she took small doses of insulin, the patient had been well until three and a half years before admission, when congestive heart failure with atrial fibrillation developed. X-ray films of the chest revealed moderate cardiac enlargement and pulmonary vascular congestion; an area of increased density, 6 cm in diameter, was evident in the left lower lobe; the right superior mediastinum appeared prominent. After the administration of digoxin, diuretics and a low-sodium diet she improved and . . .
Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder
Authors: Adrian D. Sandler, Kelly A. Sutton, Jeffrey DeWeese, Mary Alice Girardi, Victoria Sheppard, James W. Bodfish
Journal: New England Journal of Medicine (1999)

Secretin is a peptide hormone that stimulates pancreatic secretion. After recent publicity about a child with autism whose condition markedly improved after a single dose of secretin, thousands of children with autistic disorders may have received secretin injections.We conducted a double-blind, placebo-controlled trial of a single intravenous dose of synthetic human secretin in 60 children (age, 3 to 14 years) with autism or pervasive developmental disorder. The children were randomly assigned to treatment with an intravenous infusion of synthetic human secretin (0.4 microg per kilogram of body weight) or saline placebo. We used standardized behavioral measures of the primary and secondary features of autism, including the Autism Behavior Checklist, to assess the degree of impairment at base line and over the course of a four-week period after treatment.Of the 60 children, 4 could not be evaluated - 2 received secretin outside the study, and 2 did not return for follow-up. Thus, 56 children (28 in each group) completed the study. As compared with placebo, secretin treatment was not associated with significant improvements in any of the outcome measures. Among the children in the secretin group, the mean total score on the Autism Behavior Checklist at base line was 59.0 (range of possible values, 0 to 158, with a larger value corresponding to greater impairment), and among those in the placebo group it was 63.2. The mean decreases in scores over the four-week period were 8.9 in the secretin group and 17.8 in the placebo group (mean difference, -8.9; 95 percent confidence interval, -19.4 to 1.6; P=0.11). None of the children had treatment-limiting adverse effects. After they were told the results, 69 percent of the parents of the children in this study said they remained interested in secretin as a treatment for their children.A single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder.
Physical Properties of Competent and Defective States of a Murine Sarcoma (Moloney) Virus
Journal: JNCI Journal of the National Cancer Institute (1969)

Focus assays of various stocks of murine sarcoma virus (MSV) had revealed that such stocks contained, in addition to defective MSV and MLV, variable amounts of “competent” MSV which could form foci on mouse cells without coinfection by endogenous Moloney leukemia virus (MLV). The physical properties of competent MSV were examined. Ultrasonic vibration led to selective inactivation of competent MSV, whereas defective MSV or MLV was only minimally affected. In differential centrifugations or in sedimentation on sucrose gradients defective MSV showed a lower sedimentation coefficient and could be separated from competent MSV. Viral pellets prepared by high-speed centrifugation of stocks of defective MSV and endogenous MLV were found to contain competent MSV. Filtration of dilutions of crude MSV stocks through 0.45 and 0.20 μ average pore size filters gave preparations successively enriched in defective MSV. Examination of preparations of MSV at various stages of purification by the Moloney procedure indicated formation of competent MSV during high-speed pellet formation and during the final freezing of the viral preparation. These findings indicate that competent MSV consists of an interviral aggregation of MSV and MLV which can form during laboratory manipulations.
Case 32-2012
Authors: Richard J. Glassock, Leila Khorashadi, Yael B. Kushner
Journal: New England Journal of Medicine (2012)

A 35-year-old man was admitted to this hospital because of dyspnea, anemia, and renal failure. Two days earlier, dyspnea and decreased urine output had developed. Imaging revealed bilateral lung opacities, and bronchoscopy showed pulmonary hemorrhage. Diagnostic tests were performed.
P2 Platelet Reactivity as a Potential Biomarker in Idiopathic Pulmonary Fibrosis
Authors: MG Crooks, C Wright, S Fraser, AH Morice, SP Hart
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Heterogeneity of idiopathic pulmonary fibrosis (IPF) means it is difficult to identify those at highest risk of progression who are most likely to benefit from treatment. A biomarker that predicts disease activity, prognosis and treatment response would be beneficial. We previously reported increased platelet reactivity in IPF,<sup>1</sup> and here we explore whether platelet reactivity warrants further investigation as a biomarker. <h3>Methods</h3> Data were obtained from two studies: Study 1. a study of platelet reactivity in IPF; and Study 2. a pilot randomised-controlled trial of an investigational IPF treatment. Standard protocols were used to measure platelet-monocyte aggregate (PMA) formation, P-selectin expression, and fibrinogen binding in blood samples. Platelet reactivity in IPF was compared with controls. Correlation between platelet reactivity and forced vital capacity (FVC) was assessed. Study 2 data were used to assess the change in platelet reactivity in response to the intervention and correlation between baseline platelet reactivity, symptoms (KBILD) and exercise capacity (6MWD). <h3>Results</h3> Study 1 included 13 IPF patients (mean± SD, Age 70.3 ± 5.8 years, 69% male, FVC 91.9 ± 17.8% predicted) and 12 controls (Age 66.2 ± 10.2, 66.7% males). Study 2 included 19 IPF patients (Age 71.5 ± 8.7, 72% males, FVC 84.4 ± 16.8% predicted). IPF patients demonstrated significantly increased platelet reactivity compared to controls (P &lt; 0.01). Platelet reactivity and FVC did not correlate. In study 2, stimulated platelets expressed significantly less P-selectin in response to the intervention (P = 0.03). Unstimulated PMA formation moderately correlated with KBILD (r = 0.38. P = 0.01), but other platelet markers showed no correlation with symptoms or exercise capacity. <h3>Conclusion</h3> IPF patients exhibit increased platelet reactivity compared to controls. The reduction in platelet reactivity in response to an intervention may indicate responsiveness to treatment effect. Although there was no correlation between FVC and platelet activation, further investigation is warranted to assess associations between platelet reactivity and lung function decline and mortality. <h3>Reference</h3> 1 Crooks MG, Fahim A, Naseem KM, Morice AH, Hart SP. Increased platelet reactivity in idiopathic pulmonary fibrosis is medicated by a plasma factor.<i> PLoS One</i> 2014;<b>9</b>(10):e111347
Molecular Basis of Hereditary Elliptocytosis Due to Protein 4.1 Deficiency
Authors: John Conboy, Narla Mohandas, Gil Tchernia, Yuet W. Kan
Journal: New England Journal of Medicine (1986)

Hereditary elliptocytosis is a heterogeneous group of red-cell disorders characterized morphologically by oval-shaped erythrocytes. It is an infrequent but well-defined cause of hemolytic anemia. To investigate the molecular abnormality in this disorder, we examined the arrangement of the gene encoding protein 4.1, a membrane skeletal protein of human erythrocytes, in an Algerian family with hereditary elliptocytosis and severe hemolytic anemia due to complete deficiency of protein 4.1. Southern blot analysis of genomic DNA from hematologically normal and abnormal members of this family showed that the mutant gene had a DNA rearrangement upstream from the initiation codon for translation. The mRNA from the mutant locus was aberrantly spliced, and that abnormality was the most likely explanation for the deficiency of protein 4.1 in the family. We assigned the gene for erythrocyte protein 4.1 to the short arm (p) of chromosome 1, within a region from band 32 to the terminus (1p32----1pter). Other cases of hereditary elliptocytosis of unknown cause have been mapped to the same region of chromosome 1 by linkage to the Rh locus. The chromosomal location of the gene that codes for protein 4.1 suggests that hereditary elliptocytosis in one class of patients with the disorder may be caused by a mutation of this gene.
The Clinical and Laboratory Significance of Serotonin and Catechol Amines in Bananas
Authors: J. Richard Crout, Albert Sjoerdsma
Journal: New England Journal of Medicine (1959)

THE determinations of catechol amines and 5-hydroxyindoleacetic acid (5HIAA) in the urine have become relatively common laboratory procedures. These assays are useful in establishing the diagnosis of pheochromocytoma1 and malignant carcinoid2 respectively, and in addition are applied widely for research purposes. The influence of the diet on the urinary excretion of these compounds was given little attention until Anderson, Ziegler and Doeden3 demonstrated that banana feeding increases the urinary excretion of 5HIAA. Subsequently, it was shown by Waalkes et al.4 that this was due to the presence in banana pulp of 5-hydroxytryptamine (serotonin), the metabolic precursor of 5HIAA.5 The latter . . .
Training load--injury paradox: is greater preseason participation associated with lower in-season injury risk in elite rugby league players?
Authors: Johann Windt, Tim J Gabbett, Daniel Ferris, Karim M Khan
Journal: British Journal of Sports Medicine (2016)

Aim To determine whether players who completed a greater number of planned preseason training sessions were more or less likely to be injured during the competitive season. Methods A cohort of 30 elite rugby league players was prospectively studied during their 17-week preseason and 26-round competitive season. Injuries were recorded using a match time loss definition. Preseason participation was quantified as the number of ‘full’ training sessions that players completed, excluding modified, rehabilitation or missed sessions. In-season training load variables, collected using global positioning system (GPS) data, included distance covered (m), high-speed distance covered (m) and the percentage of distance covered at high speeds (%). Multilevel logistic regression models were used to determine injury likelihood in the current and subsequent week, with random intercepts for each player. Odds ratios (OR) were used as effect size measures to determine the changes in injury likelihood with (1) a 10-session increase in preseason training participation or (2) standardised changes in training load variables. Results Controlling for training load in a given week, completing 10 additional preseason sessions was associated with a 17% reduction in the odds of injury in the subsequent week (OR=0.83, 95% CI=0.70 to 0.99). Increased preseason participation was associated with a lower percentage of games missed due to injury (r=−0.40, p&lt;0.05), with 10 preseason sessions predicting a 5% reduction in the percentage of games missed. Conclusions Maximising participation in preseason training may protect elite rugby league players against in-season injury.
Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C
Authors: Philipp Blüm, Joachim Pircher, Monika Merkle, Thomas Czermak, Andrea Ribeiro, Hanna Mannell, Florian Krötz, Alexander Hennrich, Michael Spannagl, Simone Köppel, Erik Gaitzsch, Markus Wörnle
Journal: Cellular and Molecular Immunology (2016)
Case 41-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Stephen L. Curry, Robert H. Young
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 35-year-old woman was admitted to the hospital because of a pelvic mass, a productive cough, and known pulmonary adenocarcinomatous metastases.She was well until two months earlier, when a cough developed, worsened progressively, and became productive of frothy mucoid sputum. She observed painless swelling of the right leg and had diarrhea of three weeks' duration. Seven weeks before admission the patient consulted a physician, who found a tender mass in the pelvis and both lower abdominal quadrants. An x-ray film of the chest was reported to be normal. An ultrasonographic examination of the abdomen was reported . . .