tbuckley/cabot-search huggingface dataset:
Measuring the impacts of the Winter Youth Olympic Games 2012 the impact - stakeholder approach
Authors: Martin Schnitzer, Martin Kopp
Journal: British Journal of Sports Medicine (2012)

Research on mega and other large-scale events started becoming popular more than 30 years ago, especially in the field of tourism and leisure. Scholars mainly discuss the economic impact of these events1 whereas studies commissioned by event organisers often attempt to justify the use of taxpayers’ money in staging these events.2 Literature reviews show that events may also create other impacts or, what is frequently defined as legacies , in the social, environmental, infrastructural, touristic or sporting fields. Legacy …
Emerging optical methods for surveillance of Barrett's oesophagus
Authors: Matthew B Sturm, Thomas D Wang
Journal: Gut (2015)

The rapid rise in incidence of oesophageal adenocarcinoma has motivated the need for improved methods for surveillance of Barrett9s oesophagus. Early neoplasia is flat in morphology and patchy in distribution and is difficult to detect with conventional white light endoscopy (WLE). Light offers numerous advantages for rapidly visualising the oesophagus, and advanced optical methods are being developed for wide-field and cross-sectional imaging to guide tissue biopsy and stage early neoplasia, respectively. We review key features of these promising methods and address their potential to improve detection of Barrett9s neoplasia. The clinical performance of key advanced imaging technologies is reviewed, including (1) wide-field methods, such as high-definition WLE, chromoendoscopy, narrow-band imaging, autofluorescence and trimodal imaging and (2) cross-sectional techniques, such as optical coherence tomography, optical frequency domain imaging and confocal laser endomicroscopy. Some of these instruments are being adapted for molecular imaging to detect specific biological targets that are overexpressed in Barrett9s neoplasia. Gene expression profiles are being used to identify early targets that appear before morphological changes can be visualised with white light. These targets are detected in vivo using exogenous probes, such as lectins, peptides, antibodies, affibodies and activatable enzymes that are labelled with fluorescence dyes to produce high contrast images. This emerging approach has potential to provide a ‘red flag’ to identify regions of premalignant mucosa, outline disease margins and guide therapy based on the underlying molecular mechanisms of cancer progression.
Developmental contexts and sporting success: birth date and birthplace effects in national hockey league draftees 2000–2005
Authors: Joseph Baker, A Jane Logan
Journal: British Journal of Sports Medicine (2007)

To examine relative age and birth place effects in hockey players drafted to play in the National Hockey League (NHL) between 2000 and 2005 and determine whether these factors influenced when players were chosen in the draft.1013 North American draftees were evaluated from the official NHL website, which provided birthplace, date of birth and selection order in the draft. Population size was collected from Canadian and American census information. Athletes were divided into four quartiles on the basis of selection date to define age cohorts in hockey. Data between the Canadian and American players were also compared to see if the optimal city sizes differed between the two nations.Relative age and birthplace effects were found, although the optimal city size found was dissimilar to that found in previous studies. Further, there were inconsistencies between the Canadian and American data.Contextual factors such as relative age and size of birthplace have a significant effect on likelihood of being selected in the NHL draft.
The Role of Somatic Mutation of Immunoglobulin Genes in Autoimmunity
Authors: A Davidson, R Shefner, A Livneh, B Diamond
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Wild bird surveillance around outbreaks of highly pathogenic avian influenza A(H5N8) virus in the Netherlands, 2014, within the context of global flyways
Authors: J H Verhagen, H P van der Jeugd, B A Nolet, R Slaterus, S P Kharitonov, P P de Vries, O Vuong, F Majoor, T Kuiken, R A Fouchier
Journal: Eurosurveillance (2015)

Highly pathogenic avian influenza (HPAI) A(H5N8) viruses that emerged in poultry in east Asia since 2010 spread to Europe and North America by late 2014. Despite detections in migrating birds, the role of free-living wild birds in the global dispersal of H5N8 virus is unclear. Here, wild bird sampling activities in response to the H5N8 virus outbreaks in poultry in the Netherlands are summarised along with a review on ring recoveries. HPAI H5N8 virus was detected exclusively in two samples from ducks of the Eurasian wigeon species, among 4,018 birds sampled within a three months period from mid-November 2014. The H5N8 viruses isolated from wild birds in the Netherlands were genetically closely related to and had the same gene constellation as H5N8 viruses detected elsewhere in Europe, in Asia and in North America, suggesting a common origin. Ring recoveries of migratory duck species from which H5N8 viruses have been isolated overall provide evidence for indirect migratory connections between East Asia and Western Europe and between East Asia and North America. This study is useful for better understanding the role of wild birds in the global epidemiology of H5N8 viruses. The need for sampling large numbers of wild birds for the detection of H5N8 virus and H5N8-virus-specific antibodies in a variety of species globally is highlighted, with specific emphasis in north-eastern Europe, Russia and northern China.
Diabetes, Glucose, Insulin, and Heart Rate Variability
Authors: Emily B. Schroeder, Lloyd E. Chambless, Duanping Liao, Ronald J. Prineas, Gregory W. Evans, Wayne D. Rosamond, Gerardo Heiss
Journal: Diabetes Care (2005)

OBJECTIVE—To describe the progression of autonomic impairment among individuals with diabetes and pre-diabetic metabolic impairments. RESEARCH DESIGN AND METHODS—We investigated the consequence of diabetes and pre-diabetic metabolic impairments on the 9-year change in heart rate variability (HRV) in a population-based cohort of 6,245 individuals aged 45–64 years at baseline and cross-sectional associations among 9,940 individuals. RESULTS—Diabetic subjects had a more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal-to-normal R-R intervals were −0.65 (−0.69 to −0.61) for those with normal fasting glucose vs. −0.95 (−1.09 to −0.81) for diabetic subjects, in root mean square of successive differences in normal-to-normal R-R intervals −0.35 (−0.39 to −0.30) vs. −0.66 (−0.82 to −0.51), and in R-R interval 6.70 (6.37–7.04) vs. 3.89 (2.72–5.05). While we found cross-sectional associations between decreased HRV and diabetes and nondiabetic hyperinsulinemia and a weak inverse association with fasting glucose, neither impaired fasting glucose nor nondiabetic hyperinsulimenia was associated with a measurably more rapid decline in HRV than normal. CONCLUSIONS—Cardiac autonomic impairment appears to be present at early stages of diabetic metabolic impairment, and progressive worsening of autonomic cardiac function over 9 years was observed in diabetic subjects. The degree to which pre-diabetic metabolic impairments in insulin and glucose metabolism contribute to decreases in cardiac autonomic function remains to be determined.
Porphyria cutanea tarda and antibodies to hepatitis C virus
Authors: J. PH. LACOUR, I. BODOKH, J. CASTANET, S. BEKRI, J.P. ORTONNE
Journal: British Journal of Dermatology (1993)

We have studied the prevalence of hepatitis C virus antibodies (anti-HCV) in 13 patients suffering from sporadic porphyria cutanea tarda. The sera were tested by Abbott second-generation enzyme immunoassay; seropositivity was confirmed by Ortho second-generation recombinant immunoblot assay. Ten cases (76.1%) were anti-HCV positive; one patient was also seropositive for HIV. This preliminary study suggests that HCV could be a frequent triggering factor for sporadic porphyria cutanea tarda.
Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis
Authors: D S Majka, K D Deane, L A Parrish, A A Lazar, A E Baron, C W Walker, M V Rubertone, W R Gilliland, J M Norris, V M Holers
Journal: Annals of the Rheumatic Diseases (2007)

To investigate factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the preclinical phase of rheumatoid arthritis (RA) development.243 serial prediagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies.Of the 83 cases, 47 (57%) and 51 (61%) subjects had at least one prediagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of preclinical antibody appearance. Preclinical anti-CCP positivity was strongly associated with the development of erosive RA (odds ratio = 4.64; 95% confidence interval 1.71 to 12.63; p<0.01), but RF was not (p = 0.60). Additionally, as age at the time of diagnosis of RA increased the duration of prediagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In no subjects did symptom onset precede the appearance of RF or anti-CCP antibodies.The period of time that RF and anti-CCP are present before diagnosis lengthens as the age at the time of diagnosis of RA increases. This finding suggests that factors such as genetic risk or environmental exposure influencing the temporal relationship between the development of RA-related autoantibodies and clinically apparent disease onset may differ with age.
The cost of tuberculosis sequelae
Authors: Roland Diel
Journal: European Respiratory Journal (2014)

From the author: 

We thank A. Proano and co-workers for their important comments on our cost analysis of tuberculosis (TB) in the European Union [1]. As pointed out in our study, the cost calculation only refers to direct treatment costs of the disease itself under the implicit assumption that treatment success has either been gained over 24 months or, alternatively, that according to the official World Health Organization data a minor percentage of patients (shown separately for fully susceptible TB and multidrug-resistant (MDR)-TB) will die immediately afterwards. In addition, to our knowledge, the disability weight …
Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy
Authors: R E Alten, C Zerbini, S Jeka, F Irazoque, F Khatib, P Emery, A Bertasso, M Rabbia, J P Caulfield
Journal: Annals of the Rheumatic Diseases (2009)

To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX).Patients receiving stable doses of MTX were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo. The primary efficacy measure was the proportion of patients with > or =20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, Disease Activity Score (DAS)/European League Against Rheumatism (EULAR) responses and the individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing and immunology assessments.On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31% to 43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections.In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.
Gefitinib in Combination With Gemcitabine and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 1
Authors: Giuseppe Giaccone, Roy S. Herbst, Christian Manegold, Giorgio Scagliotti, Rafael Rosell, Vincent Miller, Ronald B. Natale, Joan H. Schiller, Joachim von Pawel, Anna Pluzanska, Ulrich Gatzemeier, John Grous, Judith S. Ochs, Steven D. Averbuch, Michael K. Wolf, Pamela Rennie, Abderrahim Fandi, David H. Johnson
Journal: Journal of Clinical Oncology (2004)

The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE) to standard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability.This was a phase III randomized, double-blind, placebo-controlled, multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC. All patients received up to six cycles of chemotherapy (cisplatin 80 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 of the 3-week cycle) plus either gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. Daily gefitinib or placebo was continued until disease progression. End points included overall survival (primary), time to progression, response rates, and safety evaluation.A total of 1,093 patients were enrolled. There was no difference in efficacy end points between the treatment groups: for the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo groups, respectively, median survival times were 9.9, 9.9, and 10.9 months (global ordered log-rank [GOLrank] P =.4560), median times to progression were 5.5, 5.8, and 6.0 months (GOLrank; P =.7633), and response rates were 49.7%, 50.3%, and 44.8%. No significant unexpected adverse events were seen.Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone. The reasons for this remain obscure and require further preclinical testing.
Identifying neuropathic pain in patients with head and neck cancer: use of the Leeds Assessment of Neuropathic Symptoms and Signs Scale
Authors: J. Potter, I. J Higginson, J. W Scadding, C. Quigley
Journal: Journal of the Royal Society of Medicine (2003)

The Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) is a simple bedside test in two parts—a patient-completed questionnaire and a brief clinical assessment. Its diagnostic capabilities have never been tested in patients with cancer pain. To determine these we conducted a prospective study in outpatients with head and neck cancer. All patients with pain completed the LANSS and underwent a medical assessment with a palliative care physician, whose findings were then reviewed by a pain specialist blinded to the LANSS scores. We assessed acceptability and understanding of the LANSS by patients and calculated the sensitivity and specificity of total LANSS scores and subscores derived from the patient-completed section. Of 130 patients approached, 125 took part. 25 (20%) of these had cancer related pain, mean score on an 11 point numerical rating scale 6.3 (median 6.0, range 3-10). Average age was 60 years (median 60, range 27-84); 56% were male. LANSS completion time was about five minutes, and the procedure was acceptable to all patients. The pain specialist diagnosed neuropathic pain in 14/25 patients, in 13 of whom the neuropathic pain was part of a mixed pain picture. The LANSS correctly identified 11 of these cases (sensitivity 79%; specificity 100%). The patient-completed section alone had a sensitivity of 86% and a specificity of 91%. The LANSS is a simple and suitable screening test for neuropathic pain in patients with head and neck cancer related pain, although some modifications might improve it.
IDH1 R132H Mutation Generates a Distinct Phospholipid Metabolite Profile in Glioma
Authors: Morteza Esmaeili, Bob C. Hamans, Anna C. Navis, Remco van Horssen, Tone F. Bathen, Ingrid S. Gribbestad, William P. Leenders, Arend Heerschap
Journal: Cancer Research (2014)

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma.
B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma
Authors: Ilona Kryczek, Linhua Zou, Paulo Rodriguez, Gefeng Zhu, Shuang Wei, Peter Mottram, Michael Brumlik, Pui Cheng, Tyler Curiel, Leann Myers, Andrew Lackner, Xavier Alvarez, Augusto Ochoa, Lieping Chen, Weiping Zou
Journal: The Journal of Experimental Medicine (2006)

Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.
Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure
Authors: R VENTURACLAPIER, B METTAUER, X BIGARD
Journal: Cardiovascular Research (2006)

As endurance training improves symptoms and quality of life and decreases mortality rate and hospitalization, it is increasingly recognized as a beneficial practice for heart failure (HF) patients. However, the mechanisms involved in the beneficial effects of exercise training are far from being understood and need further evaluation. Independent of hemodynamics effects, exercise training participates in tissue remodeling. While heart failure induces a generalized metabolic myopathy, adaptation to endurance training mainly improves energetic aspects of muscle function. In the present review, after presenting the main characteristics of cardiac and skeletal muscle energy metabolism and the effects of exercise training, we will discuss the evidence for the beneficial effects of endurance training on cardiac and skeletal muscle oxidative metabolism and intracellular energy transfer in HF. These beneficial effects of exercise training seen in heart failure patients are also relevant to other chronic diseases (chronic obstructive pulmonary disease, diabetes, and obesity) and even for highly sedentary or elderly individuals [Booth F.W., Chakravathy M.V., Spangenburg E.E. Exercise and gene expression: physiological regulation of the human genome through physical activity. J Physiol (Lond) 2002;543:399-411]. Physical rehabilitation is thus a major health issue for populations in industrialized countries.
New immunological approaches and cytokine targetsin asthma and allergy
Authors: R.G. Stirling, K.F. Chung
Journal: European Respiratory Journal (2000)

The aims of current asthma treatment are to suppress airway inflammation and control symptoms, and corticosteroids maintain a commanding position in this role. Steroids effectively suppress inflammation in the majority of patients but have little impact on the natural history of this disease. In severe asthmatics, corticosteroids may have relatively less beneficial effects. Recent advances in understanding the inflammatory and immunological mechanisms of asthma have indicated many potential therapeutic avenues that may prevent or reverse abnormalities that underlie asthma. As the roles of effector cells, and of signalling and adhesion molecules are better understood, the opportunities to inhibit or prevent the inflammatory cascade have increased. In addition, there have been advances in the synthesis of proteins, monoclonal antibodies and new small molecule chemical entities, which may provide valuable flexibility in the therapeutic approach to asthma. The novel immunological approaches include the prevention of T-cell activation, attempts to influence the balance of T-helper cell (Th) populations to inhibit or prevent Th2-derived cytokine expression, and the inhibition or blockade of the downstream actions of these cytokines such as effects on immunoglobulin-E and eosinophils. These approaches provide broad as well as highly specific targeting, and also prospects for prevention and reversal of immunological and inflammatory abnormalities associated with asthma. Hopefully, the development of effective antiasthma agents with effects beyond those provided by current therapies coupled with lesser side-effects will further address the unmet needs of asthma.