tbuckley/cabot-search huggingface dataset:
Detecting and developing youth athlete potential: different strokes for different folks are warranted
Authors: Haresh T Suppiah, Chee Yong Low, Michael Chia
Journal: British Journal of Sports Medicine (2015)

Sport talent identification and development (TI and TD) in youth continues to attract strong interest among coaches, sport scientists and sport administrators. TI for sport in youth with the anticipation of future elite level sport achievement is both an art and a science, and is strongly influenced by within athlete and extraneous-to-athlete factors (ecosystem of support or the lack of). The returns from investment on current TI and TD models of sport in youth are subpar in that few continue in the sport to achieve podium positions at the elite sport level in adulthood. Why, where and how one succeeds in sport, and what that success means to the athlete and stakeholders are dependent on the culture and context of the country. We advocate harnessing the power of sport to help in youth development, to be holistic in its nurturance, to allow for individual idiosyncratic expressions of the athletes, to provide for talent transfer across sport, and to facilitate key stakeholders to ‘join’ hands to work for the common interest and understanding for as many youth and adults so as to provide them with opportunities through support and coaching to compete at the different levels of competition in sport. Governments, policy makers and administrators of sport must decide, within their specific circumstances, if TI and TD in sport in youth is serving a meaningful purpose and is a viable return on investment; in short, is it mission possible or is it… a quest for the Holy Grail for a podium finish in elite level sport competition?
Extrapulmonary tuberculosis (EPTB) in Poland
Authors: Katarzyna Lewandowska, Maria Korzeniewska-Kosela, Izabela Siemion-Szczesniak, Jan Kus
Journal: European Respiratory Journal (2014)

The incidence of tuberculosis (TB) in Poland in 2012 was 19.6/100000 people, that means a significant decrease comparing to 27.5/100000 in 2002. The proportion of (EPTB) however remains stable.  Aim of the study: to characterize the group of patients with EPTB in Poland.  Methods: The analysis was based on the data from the central register of tuberculosis comprising years 2002 to 2013. The categorical variables were compared using chi-square test. Factors associated with EPTB were tested using multivariable logistic regression models.  Results: There were 101708 cases of TB registered in years 2002 to 2013, of which EPTB comprised 7.8% (7924 cases). Most frequent EPTB localizations were pleura and extrathoracic lymph nodes, followed by intrathoracic lymph nodes, miliary TB and digestive tract; meningitis was very rare.  The prevalence of EPTB in women was significantly higher than in men (10.9% vs. 6.3%, p  Conclusion: Multivariate analysis showed, that female gender, younger age and absence of alcohol abuse were independent determinants of EPTB in Poland.
HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT
Authors: Charles Huggins, Yolanda Torralba, Klaus Mainzer
Journal: The Journal of Experimental Medicine (1956)

A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic. The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added. In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions. In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor. In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of growth of the tumor until a peak was achieved; an increase of the dose above the optimal amount depressed the growth of the tumor. The stage of depression of growth was not observed in the mammary glands of these tumor-bearing rats. Many steroids which induced gestational changes in the mammary gland accelerated the growth of the tumor. Among these were estrone and progesterone in combination and 17alpha-ethinyl-19-nor-testosterone administered alone. But gestational changes developed in the mammary gland of rats treated with 4-androstene-3alpha,17beta-diol, without growth of the tumor. The evidence which we have presented proves that the mammary fibroadenoma tested had some of the functional properties of a normal mammary gland, and neoplastic traits as well. In its response to hormones it had characteristics which set it apart from all other endocrine targets of the rat.
Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre.
Authors: M T Huizing, G Giaccone, L J van Warmerdam, H Rosing, P J Bakker, J B Vermorken, P E Postmus, N van Zandwijk, M G Koolen, W W ten Bokkel Huinink, W J van der Vijgh, F J Bierhorst, A Lai, O Dalesio, H M Pinedo, C H Veenhof, J H Beijnen
Journal: Journal of Clinical Oncology (1997)

PURPOSE To investigate the pharmacokinetics and pharmacodynamics of paclitaxel (P) and carboplatin (C) in a sequence-finding and dose-escalating study in untreated non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Fifty-five chemotherapy-naive patients with NSCLC were entered onto the pharmacokinetic part of a large phase I trial in which P was administered as a 3-hour infusion at dosages of 100 to 250 mg/m2, and C over 30 minutes at dosages of 300 to 400 mg/m2. Patients were randomized for the sequence of administration, first C followed by P or vice versa. Each patient received the alternate sequence during the second and subsequent courses. RESULTS The most important hematologic toxicity encountered-was neutropenia. Hematologic toxicity was not dependent on the sequence in which P and C were administered, but there was cumulative neutropenia. Nonhematologic toxicities consisted mainly of vomiting, myalgia, and arthralgia. No sequence-dependent pharmacokinetic interactions for the P area under the concentration-time curve (P-AUC), maximal plasma concentration (P-Cmax), or time above a threshold concentration of 0.1 mumol/L (P-T &gt; or = 0.1 mumol/L) were observed. However, there was a significant difference for the metabolite 6 alpha-hydroxypaclitaxel AUC (6OHP-AUC). Higher 6OHP-AUCs were observed when C was administered before P. The mean plasma ultrafiltrate AUC of C (CpUF-AUC) at the dosage of 300 mg/m2 for the sequence C--&gt;P was 3.52 mg/mL.min (range, 1.94 to 5.83) and 3.62 mg/mL.min for the sequence P--&gt;C (range, 1.91 to 5.01), which is not significantly different (P = .55). Of 45 assessable patients, there were five major responders (three complete responders and two partial responders). Four of five responses occurred at dosages above dose level 4 (P 175 mg/m2 + C 300 mg/m2). The median survival duration was best correlated with the P dose (4.8 months for doses &lt; 175 mg/m2 v 7.9 months for doses &gt; or = 175 mg/m2, P = .07; P-T &gt; or = 0.1 mumol/L, 4.8 months for &lt; 15 hours v 8.2 months for &gt; or = 15 hours, P = .06). CONCLUSION There was no pharmacokinetic-sequence interaction between C and P in this study. A clear dose-response relation with respect to response rate and survival was observed. The pharmacokinetic parameter P-T &gt; or = 0.1 mumol/L was related to improved survival in this study.
A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer
Authors: Aki Ishikawa, Shinichiro Motohashi, Eiichi Ishikawa, Hiroki Fuchida, Kazuko Higashino, Mizuto Otsuji, Toshihiko Iizasa, Toshinori Nakayama, Masaru Taniguchi, Takehiko Fujisawa
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Human Vα24 natural killer T (NKT) cells bearing an invariant Vα24JαQ antigen receptor, the counterpart of murine Vα14 NKT cells, are activated by a specific ligand, α-galactosylceramide (αGalCer, KRN7000), in a CD1d-dependent manner. I.v. administration of αGalCer-pulsed dendritic cells (DC) induces significant activation and expansion of Vα14 NKT cells in the lung and resulting potent antitumor activities in mouse tumor metastatic models. We did a phase I dose escalation study with αGalCer-pulsed DCs in lung cancer patients. Experimental Design: Patients with advanced non–small cell lung cancer or recurrent lung cancer received i.v. injections of αGalCer-pulsed DCs (level 1: 5 × 107/m2; level 2: 2.5 × 108/m2; and level 3: 1 × 109/m2) to test the safety, feasibility, and clinical response. Immunomonitoring was also done in all completed cases. Results: Eleven patients were enrolled in this study. No severe adverse events were observed during this study in any patient. After the first and second injection of αGalCer-pulsed DCs, dramatic increase in peripheral blood Vα24 NKT cells was observed in one case and significant responses were seen in two cases receiving the level 3 dose. No patient was found to meet the criteria for partial or complete responses, whereas two cases in the level 3 group remained unchanged for more than a year with good quality of life. Conclusions: In this clinical trial, αGalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.
Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability
Authors: Michael J Demeure, David W Craig, Shripad Sinari, Tracy M Moses, Alexis Christoforides, Jennifer Dinh, Tyler Izatt, Jessica Aldrich, Ardis Decker, Angela Baker, Irene Cherni, April Watanabe, Lawrence Koep, Douglas Lake, Galen Hostetter, Jeffrey M Trent, Daniel D Von Hoff, John D Carpten
Journal: Genome Medicine (2012)

Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In rare tumors, where large-scale clinical trials are daunting, this targeted genomic approach offers a new perspective and hope for improved treatments. Cancers of the ampulla of Vater are rare tumors that comprise only about 0.2% of gastrointestinal cancers. Consequently, they are often treated as either distal common bile duct or pancreatic cancers.We analyzed DNA from a resected cancer of the ampulla of Vater and whole blood DNA from a 63 year-old man who underwent a pancreaticoduodenectomy by whole genome sequencing, achieving 37× and 40× coverage, respectively. We determined somatic mutations and structural alterations.We identified relevant aberrations, including deleterious mutations of KRAS and SMAD4 as well as a homozygous focal deletion of the PTEN tumor suppressor gene. These findings suggest that these tumors have a distinct oncogenesis from either common bile duct cancer or pancreatic cancer. Furthermore, this combination of genomic aberrations suggests a therapeutic context for dual mTOR/PI3K inhibition.Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.
PEF versus FEV1
Authors: I. GREGG;
Journal: Thorax (2000)

The assertion by Dr Thiadens and colleagues1that identification of airflow limitation and estimation of its reversibility by a bronchodilator is less reliable when measured by peak expiratory flow (PEF) than by forced expiratory volume in one second (FEV1) cannot be allowed to go unchallenged. They measured both values with a Microlab 3300 turbine spirometer, disregarding the fact that, in primary care, PEF is almost always measured by peak flow meters of variable orifice type which employ an entirely different principle and give considerably higher values. Jones and Mullee,2 who compared a similar Microlab turbine spirometer with a mini-Wright meter, found that values of PEF measured by the latter were, on average, 87 l/min higher. Hence, the values reported by Thiadens et al would have been much higher if they had been measured with a peak flow meter. To compare the reliability of PEF and FEV1 for estimating magnitude of airflow limitation, Thiadens et al expressed observed values of each as percentage predicted, using the reference values for each sex recommended by the European Respiratory Society (ERS).3 Those for predicting PEF were derived from regression equations which describe a linear fall with age and give predicted values much lower than curvilinear regressions such as those of Nunn and Gregg,4 which an ERS Working Party on PEF5 subsequently judged to be the most satisfactory reference values for … Dr H A Thiadens
Safe administration of irinotecan, oxaliplatin and raltitrexed in a DPD-deficient patient with metastatic colon cancer
Authors: J. Volk, F. Reinke, A.B.P. van Kuilenburg, A.H. van Gennip, C. Schlichting, A. Ganser, P. Schöffski
Journal: Annals of Oncology (2001)
Effects of Corticosteroids on Eosinophil Chemotaxis and Adherence
Authors: Leonard C. Altman, John S. Hill, William M. Hairfield, Michael F. Mullarkey
Journal: Journal of Clinical Investigation (1981)

Therapeutic doses of corticosteroids frequently induce eosinopenia; however, the mechanism(s) involved remain obscure. To investigate this question, we studied the effects of corticosteroids on eosinophil adherence and migration. Eosinophils from normal donors were prepared by dextran sedimentation and Hypaque gradient centrifugation to 45-96% purity. Adherence was measured by filtration of whole blood and isolated eosinophils through nylon wool columns. Before prednisone administration, adherence was 83.8±3.2% for eosinophils in heparinized blood and 82.1±3.2% for isolated eosinophils. 4 h after oral prednisone administration whole blood eosinophil adherence was reduced to 53.9±10.7%; at 24 and 48 h adherence was normal. In contrast, isolated eosinophils showed no decrease in adherence 4, 24, or 48 h after corticosteroid administration. Similarly, in vitro addition of hydrocortisone to isolated eosinophils at 0.01 and 2.0 mg/ml did not reduce adherence. Eosinophil migration was tested in modified Boyden chambers by "lower-surface" and "leading-front" methods, using zymosan-activated serum and buffered saline to assess chemotactic and random migration, respectively. In vitro incubation of eosinophils with hydrocortisone or methylprednisolone produced a dose-dependent inhibition of chemotaxis. Using lower-surface methods the minimal concentration effecting substantial inhibition was 0.01 mg/ml for both drugs. At 2.0 mg/ml hydrocortisone and methylprednisolone inhibited eosinophil chemotaxis 82.6±4.4% and 85.0±3.5%, respectively. Using leading-front chemotaxis techniques significant inhibition was detected at 0.001 mg/ml hydrocortisone. Eosinophils incubated and washed free of corticosteroids responded normally to chemoattractants, indicating that the inhibitory effect of these drugs was reversible. Hydrocortisone at 2 mg/ml inhibited random eosinophil migration, although this effect was not apparent at lower concentrations. Corticosteroids did not act as chemotactic factor inactivators and were not toxic as measured by trypan blue exclusion. Eosinophils obtained from donors who had received 40 mg of prednisone orally for four days showed normal chemotactic responses, probably reflecting the fact that the cells were washed free of plasma before testing. In contrast, incubation of eosinophils in plasma from donors who had received a 300-mg bolus of hydrocortisone induced 46.1±4.5% more inhibition of chemotaxis than did incubation in normal plasma. These results indicate that: (a) eosinophil adherence is transiently reduced following in vivo corticosteroid administration, (b) eosinophil chemotaxis is inhibited by both in vitro and in vivo administration of corticosteroids, and (c) the chemotaxis inhibiting effect is nontoxic, cell-directed, dose-dependent and reversible. Inhibition of eosinophil adherence and chemotaxis may in part explain how corticosteroids produce eosinopenia and decrease the local accumulation of eosinophils.
Civil Protection Orders and Risk of Subsequent Police-Reported Violence
Authors: Victoria L. Holt
Journal: JAMA (2002)

ContextApproximately 1.5 million US women experience intimate partner violence annually. Approximately 20% of these women obtain civil protection orders, but the effectiveness of such orders in preventing future violence is unclear.ObjectiveTo assess associations between obtaining a protection order and risk of subsequent police-reported intimate partner violence.Design, Setting, and SubjectsRetrospective cohort study of 2691 adult female residents of Seattle, Wash, with an incident of male intimate partner violence reported to the Seattle Police Department between August 1, 1998, and December 31, 1999.Main Outcome MeasureRelative risk (RR) of police-reported physical and psychological abuse in the 12 months following the index incident according to protection order status (temporary protection order, usually in effect for 2 weeks; permanent protection order, usually in effect for 12 months; or no protection order).ResultsOverall rates of police-reported physical and psychological abuse in the 12 months of follow-up were 13.5 per 100 person-years and 12.3 per 100 person-years, respectively. After controlling for cohabitation at time of index incident and index incident offense type, women with temporary protection orders in effect were more likely than women without protection orders to be psychologically abused (RR in the first 6 months after the index incident, 4.0; 95% confidence interval [CI], 2.2-7.2; RR in the entire 12 months after the index incident, 4.9; 95% CI, 2.8-8.6), while women with permanent protection orders in effect were less likely than those without orders to be physically abused (RR in the first 6 months, 0.4; 95% CI, 0.1-1.1; RR in the entire 12 months, 0.2; 95% CI, 0.1-0.8).ConclusionsPermanent, but not temporary, protection orders are associated with a significant decrease in risk of police-reported violence against women by their male intimate partners.
The lupus band: do the autoantibodies target collagen VII?
Authors: A.M. Alahlafi, P. Wordsworth, F. Wojnarowska
Journal: British Journal of Dermatology (2004)

Journal Article The lupus band: do the autoantibodies target collagen VII? Get access A.M. Alahlafi, A.M. Alahlafi Departments of Dermatology and Rheumatology, Oxford Radcliffe Hospital, Oxford OX3 7LJ, U.K Dr Abdelaziz Mohamed Alahlafi. E‐mail: hos_2005@yahoo.com Search for other works by this author on: Oxford Academic Google Scholar P. Wordsworth, P. Wordsworth Departments of Dermatology and Rheumatology, Oxford Radcliffe Hospital, Oxford OX3 7LJ, U.K Search for other works by this author on: Oxford Academic Google Scholar F. Wojnarowska F. Wojnarowska Departments of Dermatology and Rheumatology, Oxford Radcliffe Hospital, Oxford OX3 7LJ, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 3, 1 March 2004, Pages 504–510, https://doi.org/10.1046/j.1365-2133.2003.05738.x Published: 01 March 2004 Article history Accepted: 30 June 2003 Published: 01 March 2004
Life After Adjuvant Chemotherapy for Breast Cancer: The News Is Mostly Good
Authors: Belinda E. Kiely, Nicholas R.C. Wilcken, Martin R. Stockler
Journal: Journal of Clinical Oncology (2011)

There comes a time with all cancers when thoughts turn from the initial successes and costs of treatment to the containment of longterm toxicity.So it is for breast cancer now.Although we have yet to cure everyone with this disease, overall recurrence rates are low, in large part because of systemic treatments that can result in long-term adverse effects.Most survivors of breast cancer report good quality of life, but impairments of role, emotional, cognitive, and social functioning persist for years in some. 1 Fatigue, cognitive dysfunction, sleep, pain, and menopausal symptoms are more subtle than the acute toxicities of chemotherapy, but they can be chronic and debilitating.Information on the likelihood, severity, and duration of long-term problems is needed to help women make informed decisions about adjuvant systemic therapy.In this issue of Journal of Clinical Oncology, Ganz et al 2,3 report two studies on symptoms and quality of life within 1 to 2 years of primary treatment for early breast cancer.The overall findings are reassuring: post-treatment symptoms are generally mild, and quality of life recovers to baseline levels within 12 months of completing primary treatment.In the first report, Ganz et al 2 compare quality-of-life scores according to receipt of chemotherapy in a randomized trial of psychoeducational interventions.Propensity scores were used to account for differences in baseline characteristics between women who did and did not receive chemotherapy.Four weeks after completing primary treatment, women who received chemotherapy had worse general health perceptions than women who did not receive chemotherapy, but the two groups had similarly impaired ratings for other generic aspects of quality of life.Ratings for these generic aspects improved in both groups, and by 12 months there were no demonstrable differences according to chemotherapy use.However, specific symptoms, including hotflashes,musculoskeletalpain,weightproblems,andvaginalproblems, persisted in both groups of women at 12 months, with all but hot flashes being more severe among chemotherapy recipients.Methodologic caveats include the facts that this was not a randomized study, and that the final 12-month survey was not completed by 28% of the study population.However, differences in known baseline characteristics were adjusted for, and those who did not complete the survey were evenly distributed between the chemotherapy and nonchemotherapy groups, suggesting that most of the observed differences in symptoms resulted from treatment.Symptom severity was adjusted for menopausal status at baseline, but development of menopause during follow-up was not reported, so we are unable to determine the extent to which these symptoms resulted from treatment-induced menopause rather than directly from chemotherapy itself.
Factors Influencing Visual Acuity after Photocoagulation for Subfoveal Choroidal Neovascularization of Exudative Age-related Macular Degeneration
Authors: Mitsuko Yuzawa, Akiko Tamakoshi, Mika Ueha, Hiroshi Kawakubo, Masami Nakajima
Journal: Ophthalmology (1996)