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Sample records for multi-center european cohort

  1. Natural-Cause Mortality and Long-Term Exposure to Particle Components: An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project

    PubMed Central

    Hoek, Gerard; Raaschou-Nielsen, Ole; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Weinmayr, Gudrun; Hoffmann, Barbara; Wolf, Kathrin; Samoli, Evangelia; Fischer, Paul H.; Nieuwenhuijsen, Mark J.; Xun, Wei W.; Katsouyanni, Klea; Dimakopoulou, Konstantina; Marcon, Alessandro; Vartiainen, Erkki; Lanki, Timo; Yli-Tuomi, Tarja; Oftedal, Bente; Schwarze, Per E.; Nafstad, Per; De Faire, Ulf; Pedersen, Nancy L.; Östenson, Claes-Göran; Fratiglioni, Laura; Penell, Johanna; Korek, Michal; Pershagen, Göran; Eriksen, Kirsten Thorup; Overvad, Kim; Sørensen, Mette; Eeftens, Marloes; Peeters, Petra H.; Meliefste, Kees; Wang, Meng; Bueno-de-Mesquita, H. Bas; Sugiri, Dorothea; Krämer, Ursula; Heinrich, Joachim; de Hoogh, Kees; Key, Timothy; Peters, Annette; Hampel, Regina; Concin, Hans; Nagel, Gabriele; Jaensch, Andrea; Ineichen, Alex; Tsai, Ming-Yi; Schaffner, Emmanuel; Probst-Hensch, Nicole M.; Schindler, Christian; Ragettli, Martina S.; Vilier, Alice; Clavel-Chapelon, Françoise; Declercq, Christophe; Ricceri, Fulvio; Sacerdote, Carlotta; Galassi, Claudia; Migliore, Enrica; Ranzi, Andrea; Cesaroni, Giulia; Badaloni, Chiara; Forastiere, Francesco; Katsoulis, Michail; Trichopoulou, Antonia; Keuken, Menno; Jedynska, Aleksandra; Kooter, Ingeborg M.; Kukkonen, Jaakko; Sokhi, Ranjeet S.; Vineis, Paolo; Brunekreef, Bert

    2015-01-01

    , Pershagen G, Eriksen KT, Overvad K, Sørensen M, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita HB, Sugiri D, Krämer U, Heinrich J, de Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Jaensch A, Ineichen A, Tsai MY, Schaffner E, Probst-Hensch NM, Schindler C, Ragettli MS, Vilier A, Clavel-Chapelon F, Declercq C, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Vineis P, Brunekreef B. 2015. Natural-cause mortality and long-term exposure to particle components: an analysis of 19 European cohorts within the Multi-Center ESCAPE Project. Environ Health Perspect 123:525–533; http://dx.doi.org/10.1289/ehp.1408095 PMID:25712504

  2. Alcohol Consumption and Mortality in the Korean Multi-center Cancer Cohort Study

    PubMed Central

    Jung, En-Joo; Shin, Aesun; Park, Sue K.; Ma, Seung-Hyun; Cho, In-Seong; Park, Boyoung; Lee, Eun-Ha; Chang, Soung-Hoon; Shin, Hai-Rim; Kang, Daehee

    2012-01-01

    Objectives To examine the association between alcohol consumption habit, types of beverages, alcohol consumption quantity, and overall and cancer-specific mortality among Korean adults. Methods The alcohol consumption information of a total of 16 320 participants who were 20 years or older from the Korean Multi-center Cancer Cohort were analyzed to examine the association between alcohol consumption habit and mortality (median follow-up of 9.3 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) of alcohol consumption to mortality adjusting for age, sex, geographic areas, education, smoking status, and body mass index. Results Alcohol drinkers showed an increased risk for total mortality compared with never drinkers (HR, 1.72; 95% confidence interval [CI], 1.38 to 2.14 for past drinkers; HR, 1.21; 95% CI, 1.06 to 1.39 for current drinkers), while past drinkers only were associated with higher risk for cancer deaths (HR, 1.84; 95% CI, 1.34 to 2.53). The quantity of alcohol consumed per week showed a J-shaped association with risk of mortality. Relative to light drinkers (0.01 to 90 g/wk), never drinkers and heavy drinkers (>504 g/wk) had an increased risk for all-cause and cancer deaths: (HR, 1.18; 95% CI, 0.96 to 1.45) and (HR, 1.39; 95% CI, 1.05 to 1.83) for all-cause mortality; and (HR, 1.55; 95% CI, 1.15 to 2.11) and (HR, 2.07; 95% CI, 1.39 to 3.09) for all cancer mortality, respectively. Heavy drinkers (>504 g/wk) showed an elevated risk for death from stomach and liver cancers. Conclusions The present study supports the existence of a J-shaped association between alcohol consumption quantity and the risk of all-cause and cancer deaths. Heavy drinkers had an increased risk of death from cancer overall and liver and stomach cancer. PMID:23091655

  3. Therapeutic hypothermia in acute liver failure: a multi-center retrospective cohort analysis

    PubMed Central

    Karvellas, Constantine J.; Stravitz, R. Todd; Battenhouse, Holly; Lee, William M.; Schilsky, Michael L.

    2016-01-01

    Background The benefit of therapeutic hypothermia (TH) in Acute Liver Failure (ALF) has not been previously demonstrated in a controlled fashion. This study aimed to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. Methods Retrospective cohort study of ALF patients in the US ALFSG with Grade III or IV hepatic encephalopathy. TH (32°C – 35°C) was used in 97 (8%) patients; 1135 (92%) not cooled were controls. Results Intracranial pressure (ICP) was monitored in 38 (40%) TH ALF patients (vs. 22% controls, p=0.0001). Rates of bleeding (12% in both), bloodstream (17% vs. 18) and tracheal infections (21% vs. 23%, p> 0.5 for all) were similar. Unadjusted 21-day overall (62% vs. 60%) and transplant-free survival (45 vs. 39%, p>0.4 for both) were similar. Multivariable models were created for acetaminophen (APAP) (n= 582) and non-APAP (n=613) patients. For APAP patients, MELD (Odds ratio 0.91 per increment; 95% CI 0.89–0.94, p <0.001) and vasopressors (OR 0.16; 0.11–0.24, p < 0.0001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients aged < 25y (Age 25: OR 2.735; 95% CI 1.001 – 7.467) but worsened in 64y or older APAP patients (Age = 64: OR 0.167; 95%CI 0.028 – 0.999). For non-APAP patients, MELD (OR 0.93 per increment; 0.91–0.95, p < 0.0001) and vasopressors (OR 0.60; 0.40–0.90, p=0.01) were associated with worse outcomes while TH had no impact (p= 0.93). Conclusions Therapeutic hypothermia in ALF was not associated with increased bleeding or infections. While young APAP-ALF patients may benefit, TH did not consistently impact 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients. PMID:25308108

  4. Body Image in Young Gender Dysphoric Adults: A European Multi-Center Study.

    PubMed

    Becker, Inga; Nieder, Timo O; Cerwenka, Susanne; Briken, Peer; Kreukels, Baudewijntje P C; Cohen-Kettenis, Peggy T; Cuypere, GrietDe; Haraldsen, Ira R Hebold; Richter-Appelt, Hertha

    2016-04-01

    The alteration of sex-specific body features and the establishment of a satisfactory body image are known to be particularly relevant for individuals with Gender Dysphoria (GD). The aim of the study was to first develop new scales and examine the psychometric properties of the Hamburg Body Drawing Scale (Appelt & Strauß 1988). For the second part of this study, the satisfaction with different body features in young GD adults before cross-sex treatment were compared to female and male controls. Data collection took place within the context of the European Network for the Investigation of Gender Incongruence (ENIGI) including 135 female-to-male (FtMs) and 115 male-to-female (MtFs) young GD adults and 235 female and 379 male age-adjusted controls. The five female and six male body feature subscales revealed good internal consistency. The ENIGI sample reported less satisfaction with overall appearance (d = 0.30) and with all of their body features than controls, but no subgroup differences for sexual orientation (FtM and MtF) and Age of Onset (FtM) were found. Body dissatisfaction was higher with regard to sex-specific body features (largest effect sizes of d = 3.21 for Genitalia in FtMs and d = 2.85 for Androgen-responsive features and genitalia in MtFs) than with those that appeared less related to the natal sex (d = 0.64 for Facial features in FtMs and d = 0.59 for Body shape in MtFs). Not only medical body modifying interventions, but also psychosocial guidance with regard to body image might be helpful for GD individuals before transitioning. PMID:25836027

  5. European Birth Cohorts for Environmental Health Research

    PubMed Central

    Casas, Maribel; Bergström, Anna; Carmichael, Amanda; Cordier, Sylvaine; Eggesbø, Merete; Eller, Esben; Fantini, Maria P.; Fernández, Mariana F.; Fernández-Somoano, Ana; Gehring, Ulrike; Grazuleviciene, Regina; Hohmann, Cynthia; Karvonen, Anne M.; Keil, Thomas; Kogevinas, Manolis; Koppen, Gudrun; Krämer, Ursula; Kuehni, Claudia E.; Magnus, Per; Majewska, Renata; Andersen, Anne-Marie Nybo; Patelarou, Evridiki; Petersen, Maria Skaalum; Pierik, Frank H.; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Santos, Ana Cristina; Slama, Rémy; Sram, Radim J.; Thijs, Carel; Tischer, Christina; Toft, Gunnar; Trnovec, Tomáš; Vandentorren, Stephanie; Vrijkotte, Tanja G.M.; Wilhelm, Michael; Wright, John; Nieuwenhuijsen, Mark

    2011-01-01

    Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. Objectives: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother–child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother–child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12–19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health. PMID

  6. Multi center cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.

    PubMed

    Terrell, T; Abramson, R; Bostick, R; Barth, J; Sloane, R; Cantu, R; Bennett, E; Galloway, L; Erlanger, D; McKeag, D; Valentine, V; Nichols, G

    2014-09-22

    This was a multicenter prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, apolipoprotein E promoter G219T, and two Tau gene exon 6 polymorphisms (Ser53Pro and Hist47Tyr) with: (1) the risk of prospective concussion, (2) concussion severity, and (3) postconcussion neurocognitive recovery. Almost three thousand student athletes from 26 National Collegiate Athletic Association Division IA, II, III, and National Association of Intercollegiate Athletics academic institutions in the United States met inclusion criteria for this study. We assessed multiple variables including, gender, sport, family history of traumatic brain injury, history of mental illness, history of migraine headache, and baseline and postconcussion neuropsychological test results. Reported concussions were evaluated with multiple instruments including number of symptoms and symptom severity. Additionally, we gathered data via a questionnaire pertaining to medical history, demographics, and sportrelated information, and blood/saliva samples were collected for genetic analysis, and we conducted neuropsychological testing using Headminder and ImPACT software. The goal of this paper is to share our experiences conducting a large prospective cohort study. We recommend that future research include metaanalyses of various traumatic brain injury studies to increase power. Collaborative research is very likely needed given the nature of this study population. PMID:25242101

  7. Retrospective benzene exposure assessment for a multi-center case-cohort study of benzene-exposed workers in China.

    PubMed

    Portengen, Lützen; Linet, Martha S; Li, Gui-Lan; Lan, Qing; Dores, Graça M; Ji, Bu-Tian; Hayes, Richard B; Yin, Song-Nian; Rothman, Nathaniel; Vermeulen, Roel

    2016-05-01

    Quality of exposure assessment has been shown to be related to the ability to detect risk of lymphohematopoietic disorders in epidemiological investigations of benzene, especially at low levels of exposure. We set out to build a statistical model for reconstructing exposure levels for 2898 subjects from 501 factories that were part of a nested case-cohort study within the NCI-CAPM cohort of more than 110,000 workers. We used a hierarchical model to allow for clustering of measurements by factory, workshop, job, and date. To calibrate the model we used historical routine monitoring data. Measurements below the limit of detection were accommodated by constructing a censored data likelihood. Potential non-linear and industry-specific time-trends and predictor effects were incorporated using regression splines and random effects. A partial validation of predicted exposures in 2004/2005 was performed through comparison with full-shift measurements from an exposure survey in facilities that were still open. Median cumulative exposure to benzene at age 50 for subjects that ever held an exposed job (n=1175) was 509 mg/m(3) years. Direct comparison of model estimates with measured full-shift personal exposure in the 2004/2005 survey showed moderate correlation and a potential downward bias at low (<1 mg/m(3)) exposure estimates. The modeling framework enabled us to deal with the data complexities generally found in studies using historical exposure data in a comprehensive way and we therefore expect to be able to investigate effects at relatively low exposure levels. PMID:26264985

  8. Quality of Life and its Determinants in a Multi-Center Cohort of Children with Alagille Syndrome

    PubMed Central

    Kamath, Binita M.; Chen, Zhen; Romero, Rene; Fredericks, Emily M.; Alonso, Estella M.; Arnon, Ronen; Heubi, James; Hertel, Paula M.; Karpen, Saul J.; Loomes, Kathleen M.; Murray, Karen F.; Rosenthal, Philip; Schwarz, Kathleen B.; Subbarao, Girish; Teckman, Jeffrey H.; Turmelle, Yumirle P.; Wang, Kasper S.; Sherker, Averell H.; Sokol, Ronald J.; Magee, John C.

    2015-01-01

    Objectives To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS. Study design Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory™ (PedsQL) questionnaires were administered to 70 ALGS, 95 alpha-1-antitrypsin deficiency (A1ATD) and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent-proxy PedsQL scores were recorded for children aged 2-18 (98 ALGS, 123 A1ATD, 68 IHC). Results Mean ages and total bilirubin (mg/dL) were: ALGS 9.4y; 4.4, A1ATD 9.5y; 0.7, IHC 10.3y; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs. 83 p=0.001). Children with ALGS and IHC were similar, except in physical scores (73 vs. 79 p=0.05). ALGS parents perceived their children to have worse HRQOL than A1ATD (p<=0.001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated INR and an intra-cardiac defect were predictive of poor parental scores (p<=0.05). In multivariate analysis, only weight z-score remained significant for child and parent-reported scores. Conclusions HRQOL is impaired in ALGS compared with healthy and children with A1ATD, similar to IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL. PMID:26059338

  9. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study

    PubMed Central

    Simon, Tamara D.; Butler, Jerry; Whitlock, Kathryn B.; Browd, Samuel R.; Holubkov, Richard; Kestle, John R.W.; Kulkarni, Abhaya V.; Langley, Marcie; Limbrick, David D.; Mayer-Hamblett, Nicole; Tamber, Mandeep; Wellons, John C.; Whitehead, William E.; Riva-Cambrin, Jay

    2014-01-01

    Objective To quantify the extent to which revision(s) of cerebrospinal fluid (CSF) shunt are associated with increased risk of CSF shunt infection, after adjusting for patient factors that may contribute to infection risk. Study design We used the HCRN registry to assemble a large prospective six center cohort of 1,036 children undergoing initial CSF shunt placement between April 2008 and January 2012. The primary outcome of interest was first CSF shunt infection. Data for initial CSF shunt placement and all subsequent CSF shunt revisions prior to first CSF shunt infection, where applicable, were obtained. The risk of first infection was estimated using a multivariable Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI). Results Of the 102 children who developed first infection within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions. Baseline factors independently associated with risk of first infection included: gastrostomy tube (HR 2.0, 95% CI: 1.1, 3.3), age 6–12 months (HR 0.3, 95% CI: 0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI: 0.2, 0.9). After controlling for baseline factors, infection risk was most significantly associated with the need for revision (1 revision vs. none, HR 3.9, 95% CI: 2.2, 6.5; ≥2 revisions, HR 13.0, 95% CI: 6.5, 24.9). Conclusions This study quantifies the elevated risk of infection associated with shunt revisions observed in clinical practice. To reduce risk of infection risk further work should optimize revision procedures. PMID:24661340

  10. Perinatal Exposure to Traffic-Related Air Pollution and Atopy at 1 Year of Age in a Multi-Center Canadian Birth Cohort Study

    PubMed Central

    Allen, Ryan W.; Becker, Allan; Brook, Jeffrey R.; Mandhane, Piush; Scott, James A.; Sears, Malcolm R.; Subbarao, Padmaja; Takaro, Tim K.; Turvey, Stuart E.; Brauer, Michael

    2015-01-01

    , Brauer M. 2015. Perinatal exposure to traffic-related air pollution and atopy at 1 year of age in a multi-center Canadian birth cohort study. Environ Health Perspect 123:902–908; http://dx.doi.org/10.1289/ehp.1408700 PMID:25826816

  11. No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study

    PubMed Central

    Antoniou, Antonis C.; Llopis, Trinidad Caldes; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Couch, Fergus J.; Pereira, Lutecia H. Mateus; Greene, Mark H.; Andrulis, Irene L.; Pasche, Boris; Kaklamani, Virginia; Hamann, Ute; Szabo, Csilla; Peock, Susan; Cook, Margaret; Harrington, Patricia A.; Donaldson, Alan; Male, Allison M.; Gardiner, Carol Anne; Gregory, Helen; Side, Lucy E.; Robinson, Anne C.; Emmerson, Louise; Ellis, Ian; Peyrat, Jean-Philippe; Fournier, Joëlle; Vennin, Philippe; Adenis, Claude; Muller, Danièle; Fricker, Jean-Pierre; Longy, Michel; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Kast, Karin; Schaefer, Dieter; Froster, Ursula G.; Chenevix-Trench, Georgia; Easton, Douglas F.

    2008-01-01

    Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92–1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81–1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. PMID:18523885

  12. Validation of Single Nucleotide Polymorphisms (SNPs) Associated with Acute Rejection in Kidney Transplant Recipients Using a Large Multi-Center Cohort

    PubMed Central

    Oetting, William S.; Schladt, David P.; Leduc, Robert E.; Jacobson, Pamala A.; Guan, Weihua; Matas, Arthur J.; Israni, Ajay

    2011-01-01

    There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with a p-value of 0.011 in a race adjusted analysis and 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest p-value of 0.044 using multiple variable analysis which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR. PMID:21955043

  13. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study†

    PubMed Central

    Cheung, Y. T.; Ng, T.; Shwe, M.; Ho, H. K.; Foo, K. M.; Cham, M. T.; Lee, J. A.; Fan, G.; Tan, Y. P.; Yong, W. S.; Madhukumar, P.; Loo, S. K.; Ang, S. F.; Wong, M.; Chay, W. Y.; Ooi, W. S.; Dent, R. A.; Yap, Y. S.; Ng, R.; Chan, A.

    2015-01-01

    Background Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. Patients and methods Chemotherapy-receiving breast cancer patients (stages I–III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte–macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder™) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. Results Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: −0.78; 95% confidence interval (CI) −1.34 to −0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). Conclusions While elevated concentrations of IL-6 and IL-1β were

  14. Joubert syndrome: genotyping a Northern European patient cohort.

    PubMed

    Kroes, Hester Y; Monroe, Glen R; van der Zwaag, Bert; Duran, Karen J; de Kovel, Carolien G; van Roosmalen, Mark J; Harakalova, Magdalena; Nijman, Ies J; Kloosterman, Wigard P; Giles, Rachel H; Knoers, Nine V A M; van Haaften, Gijs

    2016-02-01

    Joubert syndrome (JBS) is a rare neurodevelopmental disorder belonging to the group of ciliary diseases. JBS is genetically heterogeneous, with >20 causative genes identified to date. A molecular diagnosis of JBS is essential for prediction of disease progression and genetic counseling. We developed a targeted next-generation sequencing (NGS) approach for parallel sequencing of 22 known JBS genes plus 599 additional ciliary genes. This method was used to genotype a cohort of 51 well-phenotyped Northern European JBS cases (in some of the cases, Sanger sequencing of individual JBS genes had been performed previously). Altogether, 21 of the 51 cases (41%) harbored biallelic pathogenic mutations in known JBS genes, including 14 mutations not previously described. Mutations in C5orf42 (12%), TMEM67 (10%), and AHI1 (8%) were the most prevalent. C5orf42 mutations result in a purely neurological Joubert phenotype, in one case associated with postaxial polydactyly. Our study represents a population-based cohort of JBS patients not enriched for consanguinity, providing insight into the relative importance of the different JBS genes in a Northern European population. Mutations in C5orf42 are relatively frequent (possibly due to a Dutch founder mutation) and mutations in CEP290 are underrepresented compared with international cohorts. Furthermore, we report a case with heterozygous mutations in CC2D2A and B9D1, a gene associated with the more severe Meckel-Gruber syndrome that was recently published as a potential new JBS gene, and discuss the significance of this finding. PMID:25920555

  15. Drug use in children: cohort study in three European countries

    PubMed Central

    Verhamme, Katia M C; Nicolosi, Alfredo; Murray, Macey L; Neubert, Antje; Caudri, Daan; Picelli, Gino; Sen, Elif Fatma; Giaquinto, Carlo; Cantarutti, Luigi; Baiardi, Paola; Felisi, Maria-Grazia; Ceci, Adriana; Wong, Ian C K

    2008-01-01

    Objective To provide an overview of drug use in children in three European countries. Design Retrospective cohort study, 2000-5. Setting Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). Participants 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). Main outcome measure Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. Results Three levels of drug use could be distinguished in the study population: high (>10/100 children per year), moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. Conclusion This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs. PMID:19029175

  16. Elliptic genera from multi-centers

    NASA Astrophysics Data System (ADS)

    Gaddam, Nava

    2016-05-01

    I show how elliptic genera for various Calabi-Yau threefolds may be understood from supergravity localization using the quantization of the phase space of certain multi-center configurations. I present a simple procedure that allows for the enumeration of all multi-center configurations contributing to the polar sector of the elliptic genera — explicitly verifying this in the cases of the quintic in {P} 4, the sextic in {W}{P} (2,1,1,1,1), the octic in {W}{P} (4,1,1,1,1) and the dectic in {W}{P} (5,2,1,1,1). With an input of the corresponding `single-center' indices (Donaldson-Thomas invariants), the polar terms have been known to determine the elliptic genera completely. I argue that this multi-center approach to the low-lying spectrum of the elliptic genera is a stepping stone towards an understanding of the exact microscopic states that contribute to supersymmetric single center black hole entropy in {N} = 2 supergravity.

  17. Environmental exposure assessment in European birth cohorts: results from the ENRIECO project

    PubMed Central

    2013-01-01

    Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research

  18. Implementation and Operational Research: Computer-Assisted Intervention for Safer Sex in HIV-Positive Men Having Sex With Men: Findings of a European Randomized Multi-Center Trial

    PubMed Central

    Platteau, Tom; Bogner, Johannes; Buyze, Jozefien; Dec-Pietrowska, Joanna; Dias, Sonia; Newbury-Helps, John; Kocsis, Agnes; Mueller, Matthias; Rojas, Daniela; Stanekova, Danica; van Lankveld, Jacques; Colebunders, Robert

    2016-01-01

    Objective: Men who have sex with men (MSM) are the key population most affected by HIV in Europe. We performed the first European multicenter, simple-randomized parallel-group study to test the effectiveness of a theory-guided computer-assisted intervention to improve safer sex among HIV-positive men who have sex with men. Methods: Between February, 2011 and February, 2013, 112 participants were enrolled in 8 different European HIV-care settings. Intervention participants received 3 individual counseling sessions facilitated by trained service providers using computer-assisted tools. The control-group received sexual health advice delivered as part of regular HIV care. Outcome behavior (self-reported condom use at last intercourse; combined HIV transmission risk score), its influencing factors, and mediating variables were assessed at baseline, and at 3 and 6 months follow-up. Mixed effects models were used to compare primary outcomes (condom use at last intercourse, HIV transmission risk score), and mediation analysis to explore intervention effects. Results: Condom use at last intercourse increased more among intervention than control participants at 3 months follow-up (odds ratio of 3.83; P = 0.03), but not significantly at 6 months follow-up. Intervention participants reported a lower transmission risk at 3 months follow-up than controls (odds ratio compared with baseline of 11.53 and 1.28, respectively; P = 0.008), but this effect became nonsignificant at 6 months. Intervention effects were mediated by the proximal variables, self-efficacy to negotiate condom use and condom attitudes. Conclusions: This intervention showed short-term effectiveness. The intervention should be replicated in other settings, eventually investigating if booster-counseling sessions would yield a longer lasting effect. PMID:26866955

  19. No association between typical European mitochondrial variation and prostate cancer risk in a Spanish cohort.

    PubMed

    Fachal, Laura; Gómez-Caamaño, Antonio; Alvarez Iglesias, Vanesa; Gómez Carballa, Alberto; Calvo, Patricia; Salas, Antonio; Vega, Ana

    2014-07-01

    Mitochondrial common variants (mtSNPs) and the haplogroups defined by them have been inconsistently correlated with increased prostate cancer risk. Here we aimed to investigate the influence of the mitochondrial genetic background on prostate cancer. A total of 15 single-nucleotide polymorphisms (SNPs) representing the common European branches of the mtDNA phylogeny were analyzed in a cohort of 620 Spanish prostate cancer patients and 616 matched population-based controls. Association tests were computed on mtSNPs and haplogroups. None of the evaluated mtSNPs or haplogroups were statistically associated with prostate cancer risk in our Spanish cohort. We show that previous association findings do not rest on solid grounds given that all of them (i) were based on underpowered studies, (ii) did not control for population stratification, (iii) lacked replication/confirmation cohorts, and (iv) and did not control for multiple test corrections. Taken together, a critical reassessment of the previous literature and the results obtained in the present study suggest that mtDNA common European variants are not correlated with increases in the risk for prostate cancer. PMID:24898828

  20. Mortality Prediction after the First Year of Kidney Transplantation: An Observational Study on Two European Cohorts

    PubMed Central

    Lorent, Marine; Giral, Magali; Pascual, Manuel; Koller, Michael T.; Steiger, Jürg; Trébern-Launay, Katy; Legendre, Christophe; Kreis, Henri; Mourad, Georges; Garrigue, Valérie; Rostaing, Lionel; Kamar, Nassim; Kessler, Michèle; Ladrière, Marc; Morelon, Emmanuel; Buron, Fanny; Golshayan, Dela; Foucher, Yohann

    2016-01-01

    After the first year post transplantation, prognostic mortality scores in kidney transplant recipients can be useful for personalizing medical management. We developed a new prognostic score based on 5 parameters and computable at 1-year post transplantation. The outcome was the time between the first anniversary of the transplantation and the patient’s death with a functioning graft. Afterwards, we appraised the prognostic capacities of this score by estimating time-dependent Receiver Operating Characteristic (ROC) curves from two prospective and multicentric European cohorts: the DIVAT (Données Informatisées et VAlidées en Transplantation) cohort composed of patients transplanted between 2000 and 2012 in 6 French centers; and the STCS (Swiss Transplant Cohort Study) cohort composed of patients transplanted between 2008 and 2012 in 6 Swiss centers. We also compared the results with those of two existing scoring systems: one from Spain (Hernandez et al.) and one from the United States (the Recipient Risk Score, RRS, Baskin-Bey et al.). From the DIVAT validation cohort and for a prognostic time at 10 years, the new prognostic score (AUC = 0.78, 95%CI = [0.69, 0.85]) seemed to present significantly higher prognostic capacities than the scoring system proposed by Hernandez et al. (p = 0.04) and tended to perform better than the initial RRS (p = 0.10). By using the Swiss cohort, the RRS and the the new prognostic score had comparable prognostic capacities at 4 years (AUC = 0.77 and 0.76 respectively, p = 0.31). In addition to the current available scores related to the risk to return in dialysis, we recommend to further study the use of the score we propose or the RRS for a more efficient personalized follow-up of kidney transplant recipients. PMID:27152510

  1. Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

    PubMed

    Becker, Jessica; Czamara, Darina; Scerri, Tom S; Ramus, Franck; Csépe, Valéria; Talcott, Joel B; Stein, John; Morris, Andrew; Ludwig, Kerstin U; Hoffmann, Per; Honbolygó, Ferenc; Tóth, Dénes; Fauchereau, Fabien; Bogliotti, Caroline; Iannuzzi, Stéphanie; Chaix, Yves; Valdois, Sylviane; Billard, Catherine; George, Florence; Soares-Boucaud, Isabelle; Gérard, Christophe-Loïc; van der Mark, Sanne; Schulz, Enrico; Vaessen, Anniek; Maurer, Urs; Lohvansuu, Kaisa; Lyytinen, Heikki; Zucchelli, Marco; Brandeis, Daniel; Blomert, Leo; Leppänen, Paavo H T; Bruder, Jennifer; Monaco, Anthony P; Müller-Myhsok, Bertram; Kere, Juha; Landerl, Karin; Nöthen, Markus M; Schulte-Körne, Gerd; Paracchini, Silvia; Peyrard-Janvid, Myriam; Schumacher, Johannes

    2014-05-01

    Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects. PMID:24022301

  2. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort.

    PubMed

    Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Aleksandrova, Krasimira; Bamia, Christina; Lagiou, Pagona; Laursen, Anne Sofie Dam; Hansen, Louise; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; His, Mathilde; Boeing, Heiner; Katzke, Verena; Kühn, Tilman; Trichopoulou, Antonia; Valanou, Elissavet; Kritikou, Maria; Masala, Giovanna; Panico, Salvatore; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Bueno-de-Mesquita, H B As; Peeters, Petra H; Hjartåker, Anette; Skeie, Guri; Weiderpass, Elisabete; Ardanaz, Eva; Bonet, Catalina; Chirlaque, Maria-Dolores; Dorronsoro, Miren; Quirós, J Ramón; Johansson, Ingegerd; Ohlsson, Bodil; Sjöberg, Klas; Wennberg, Maria; Khaw, Kay-Tee; Travis, Ruth C; Wareham, Nick; Ferrari, Pietro; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J; Gunter, Marc; Lu, Yunxia; Jenab, Mazda

    2015-12-01

    The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk. PMID:26081477

  3. Cosmic radiation and cancer mortality among airline pilots: results from a European cohort study (ESCAPE).

    PubMed

    Langner, I; Blettner, M; Gundestrup, M; Storm, H; Aspholm, R; Auvinen, A; Pukkala, E; Hammer, G P; Zeeb, H; Hrafnkelsson, J; Rafnsson, V; Tulinius, H; De Angelis, G; Verdecchia, A; Haldorsen, T; Tveten, U; Eliasch, H; Hammar, N; Linnersjö, A

    2004-02-01

    Cosmic radiation is an occupational risk factor for commercial aircrews. In this large European cohort study (ESCAPE) its association with cancer mortality was investigated on the basis of individual effective dose estimates for 19,184 male pilots. Mean annual doses were in the range of 2-5 mSv and cumulative lifetime doses did not exceed 80 mSv. All-cause and all-cancer mortality was low for all exposure categories. A significant negative risk trend for all-cause mortality was seen with increasing dose. Neither external and internal comparisons nor nested case-control analyses showed any substantially increased risks for cancer mortality due to ionizing radiation. However, the number of deaths for specific types of cancer was low and the confidence intervals of the risk estimates were rather wide. Difficulties in interpreting mortality risk estimates for time-dependent exposures are discussed. PMID:14648170

  4. Genomic diversity of human papillomavirus genotype 53 in an ethnogeographically closed cohort of white European women.

    PubMed

    Kocjan, Bostjan J; Seme, Katja; Mocilnik, Tina; Jancar, Nina; Vrtacnik-Bokal, Eda; Poljak, Mario

    2007-04-01

    Human papillomavirus (HPV) genotype 53 is classified taxonomically in alpha HPV genus-species 6, together with HPV-30, HPV-56, and HPV-66 and is considered to be one of three "probable high-risk" HPV genotypes. Recent worldwide comparison of 44 isolates of HPV-53 showed the existence of nine long control region (LCR) genomic variants, which formed a phylogenetic tree with two deep dichotomic branches. In order to investigate further the genomic diversity of HPV-53, a total of 94 isolates of HPV-53 obtained from an ethnogeographically closed cohort of 70 white European women was analyzed. The identification and characterization of HPV-53 genomic variants was based on analysis of three different HPV genomic regions: LCR, E6 and E7. A higher genomic diversity of HPV-53 was identified in the ethnogeographically closed cohort of white European women than has been reported previously on isolates collected worldwide. Altogether, 19 HPV-53 genomic variants, composed of 13 LCR, 13 E6, and 5 E7 genomic variants, were identified. Eleven out of 13 LCR, all E6, and four out of five E7 genomic variants were described for the first time. The present study confirmed dichotomic phylogeny of HPV-53 described previously and, in addition, showed for the first time that after a dichotomic split, both groups of HPV-53 genomic variants formed star-like phylogenetic clusters. In women with persistent HPV-53 infection, HPV-53 genomic variants remained unchanged for up to 51 months. In rare cases, infection with multiple HPV-53 genomic variants is possible. Taking into account the results of this and previous studies, at least 26 different HPV-53 genomic variants exist today. PMID:17311338

  5. Clinicopathological characteristics of RHOA mutations in a Central European gastric cancer cohort.

    PubMed

    Röcken, Christoph; Behrens, Hans-Michael; Böger, Christine; Krüger, Sandra

    2016-01-01

    Genomically stable gastric cancers (GCs) are enriched for the diffuse phenotype and hotspot mutations of RHOA. Here we aimed to validate the occurrence, phenotype and clinicopathological characteristics of RHOA mutant GCs in an independent Central European GC cohort consisting of 415 patients. The RHOA genotype (exon 2 and 3) was correlated with various genotypic, phenotypic and clinicopathological patient characteristics. Sixteen (3.9%) tumours had a RHOA mutation including four hitherto unreported mutations, that is, p.G17Efs*24, p.V24F, p.T37A and p.L69R. RHOA mutation was more prevalent in women (5.4% vs 2.8%), distal GCs (4.5% vs 2.4%), in poorly differentiated GCs (G3/G4; 4.8% vs 1.1%), T1/T2 tumours (6.2% vs 3.1%) and lacked distant metastases. Nine RHOA mutant GCs had a diffuse, four an intestinal, two an unclassified and one a mixed Laurén phenotype. KRAS and RHOA mutations were mutually exclusive. A single case showed both a RHOA and a PIK3CA mutation. No significant difference was found in the overall survival between RHOA mutant and wildtype GCs. Our study confirms the occurrence and clinicopathological characteristics of RHOA hotspot mutations in an independent patient cohort. However, we found no evidence for a prognostic or growth advantageous effect of RHOA mutations in GC. PMID:26251521

  6. Clinicopathological characteristics of RHOA mutations in a Central European gastric cancer cohort

    PubMed Central

    Röcken, Christoph; Behrens, Hans-Michael; Böger, Christine; Krüger, Sandra

    2016-01-01

    Genomically stable gastric cancers (GCs) are enriched for the diffuse phenotype and hotspot mutations of RHOA. Here we aimed to validate the occurrence, phenotype and clinicopathological characteristics of RHOA mutant GCs in an independent Central European GC cohort consisting of 415 patients. The RHOA genotype (exon 2 and 3) was correlated with various genotypic, phenotypic and clinicopathological patient characteristics. Sixteen (3.9%) tumours had a RHOA mutation including four hitherto unreported mutations, that is, p.G17Efs*24, p.V24F, p.T37A and p.L69R. RHOA mutation was more prevalent in women (5.4% vs 2.8%), distal GCs (4.5% vs 2.4%), in poorly differentiated GCs (G3/G4; 4.8% vs 1.1%), T1/T2 tumours (6.2% vs 3.1%) and lacked distant metastases. Nine RHOA mutant GCs had a diffuse, four an intestinal, two an unclassified and one a mixed Laurén phenotype. KRAS and RHOA mutations were mutually exclusive. A single case showed both a RHOA and a PIK3CA mutation. No significant difference was found in the overall survival between RHOA mutant and wildtype GCs. Our study confirms the occurrence and clinicopathological characteristics of RHOA hotspot mutations in an independent patient cohort. However, we found no evidence for a prognostic or growth advantageous effect of RHOA mutations in GC. PMID:26251521

  7. LORIS: a web-based data management system for multi-center studies

    PubMed Central

    Das, Samir; Zijdenbos, Alex P.; Harlap, Jonathan; Vins, Dario; Evans, Alan C.

    2012-01-01

    Longitudinal Online Research and Imaging System (LORIS) is a modular and extensible web-based data management system that integrates all aspects of a multi-center study: from heterogeneous data acquisition (imaging, clinical, behavior, and genetics) to storage, processing, and ultimately dissemination. It provides a secure, user-friendly, and streamlined platform to automate the flow of clinical trials and complex multi-center studies. A subject-centric internal organization allows researchers to capture and subsequently extract all information, longitudinal or cross-sectional, from any subset of the study cohort. Extensive error-checking and quality control procedures, security, data management, data querying, and administrative functions provide LORIS with a triple capability (1) continuous project coordination and monitoring of data acquisition (2) data storage/cleaning/querying, (3) interface with arbitrary external data processing “pipelines.” LORIS is a complete solution that has been thoroughly tested through a full 10 year life cycle of a multi-center longitudinal project1 and is now supporting numerous international neurodevelopment and neurodegeneration research projects. PMID:22319489

  8. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

    PubMed

    Shaw, Dominick E; Sousa, Ana R; Fowler, Stephen J; Fleming, Louise J; Roberts, Graham; Corfield, Julie; Pandis, Ioannis; Bansal, Aruna T; Bel, Elisabeth H; Auffray, Charles; Compton, Chris H; Bisgaard, Hans; Bucchioni, Enrica; Caruso, Massimo; Chanez, Pascal; Dahlén, Barbro; Dahlen, Sven-Erik; Dyson, Kerry; Frey, Urs; Geiser, Thomas; Gerhardsson de Verdier, Maria; Gibeon, David; Guo, Yi-Ke; Hashimoto, Simone; Hedlin, Gunilla; Jeyasingham, Elizabeth; Hekking, Pieter-Paul W; Higenbottam, Tim; Horváth, Ildikó; Knox, Alan J; Krug, Norbert; Erpenbeck, Veit J; Larsson, Lars X; Lazarinis, Nikos; Matthews, John G; Middelveld, Roelinde; Montuschi, Paolo; Musial, Jacek; Myles, David; Pahus, Laurie; Sandström, Thomas; Seibold, Wolfgang; Singer, Florian; Strandberg, Karin; Vestbo, Jorgen; Vissing, Nadja; von Garnier, Christophe; Adcock, Ian M; Wagers, Scott; Rowe, Anthony; Howarth, Peter; Wagener, Ariane H; Djukanovic, Ratko; Sterk, Peter J; Chung, Kian Fan

    2015-11-01

    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach. PMID:26357963

  9. Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project

    PubMed Central

    Forastiere, Francesco; Stafoggia, Massimo; Andersen, Zorana J; Badaloni, Chiara; Beelen, Rob; Caracciolo, Barbara; de Faire, Ulf; Erbel, Raimund; Eriksen, Kirsten T; Fratiglioni, Laura; Galassi, Claudia; Hampel, Regina; Heier, Margit; Hennig, Frauke; Hilding, Agneta; Hoffmann, Barbara; Houthuijs, Danny; Jöckel, Karl-Heinz; Korek, Michal; Lanki, Timo; Leander, Karin; Magnusson, Patrik K E; Migliore, Enrica; Ostenson, Caes-Göran; Overvad, Kim; Pedersen, Nancy L; J, Juha Pekkanen; Penell, Johanna; Pershagen, Göran; Pyko, Andrei; Raaschou-Nielsen, Ole; Ranzi, Andrea; Ricceri, Fulvio; Sacerdote, Carlotta; Salomaa, Veikko; Swart, Wim; Turunen, Anu W; Vineis, Paolo; Weinmayr, Gudrun; Wolf, Kathrin; de Hoogh, Kees; Hoek, Gerard; Brunekreef, Bert; Peters, Annette

    2014-01-01

    Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m3 increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m3 for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m3 increase in PM2.5) and below 40 μg/m3 for PM10 (1.12, 1.00 to 1.27, for 10 μg/m3 increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European

  10. Elemental Constituents of Particulate Matter and Newborn’s Size in Eight European Cohorts

    PubMed Central

    Pedersen, Marie; Gehring, Ulrike; Beelen, Rob; Wang, Meng; Giorgis-Allemand, Lise; Andersen, Anne-Marie Nybo; Basagaña, Xavier; Bernard, Claire; Cirach, Marta; Forastiere, Francesco; de Hoogh, Kees; Gruzieva, Olena; Hoek, Gerard; Jedynska, Aleksandra; Klümper, Claudia; Kooter, Ingeborg M.; Krämer, Ursula; Kukkonen, Jaakko; Porta, Daniela; Postma, Dirkje S.; Raaschou-Nielsen, Ole; van Rossem, Lenie; Sunyer, Jordi; Sørensen, Mette; Tsai, Ming-Yi; Vrijkotte, Tanja G. M.; Wilhelm, Michael; Nieuwenhuijsen, Mark J.; Pershagen, Göran; Brunekreef, Bert; Kogevinas, Manolis; Slama, Rémy

    2015-01-01

    Background The health effects of suspended particulate matter (PM) may depend on its chemical composition. Associations between maternal exposure to chemical constituents of PM and newborn’s size have been little examined. Objective We aimed to investigate the associations of exposure to elemental constituents of PM with term low birth weight (LBW; weight < 2,500 g among births after 37 weeks of gestation), mean birth weight, and head circumference, relying on standardized fine-scale exposure assessment and with extensive control for potential confounders. Methods We pooled data from eight European cohorts comprising 34,923 singleton births in 1994–2008. Annual average concentrations of elemental constituents of PM ≤ 2.5 and ≤ 10 μm (PM2.5 and PM10) at maternal home addresses during pregnancy were estimated using land-use regression models. Adjusted associations between each birth measurement and concentrations of eight elements (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) were calculated using random-effects regression on pooled data. Results A 200-ng/m3 increase in sulfur in PM2.5 was associated with an increased risk of LBW (adjusted odds ratio = 1.36; 95% confidence interval: 1.17, 1.58). Increased nickel and zinc in PM2.5 concentrations were also associated with an increased risk of LBW. Head circumference was reduced at higher exposure to all elements except potassium. All associations with sulfur were most robust to adjustment for PM2.5 mass concentration. All results were similar for PM10. Conclusion Sulfur, reflecting secondary combustion particles in this study, may adversely affect LBW and head circumference, independently of particle mass. Citation Pedersen M, Gehring U, Beelen R, Wang M, Giorgis-Allemand L, Andersen AM, Basagaña X, Bernard C, Cirach M, Forastiere F, de Hoogh K, Gražulevičienė R, Gruzieva O, Hoek G, Jedynska A, Klümper C, Kooter IM, Krämer U, Kukkonen J, Porta D, Postma DS, Raaschou-Nielsen O

  11. Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

    PubMed

    Engeset, Dagrun; Braaten, Tonje; Teucher, Birgit; Kühn, Tilman; Bueno-de-Mesquita, H B; Leenders, Max; Agudo, Antonio; Bergmann, Manuela M; Valanou, Elisavet; Naska, Androniki; Trichopoulou, Antonia; Key, Timothy J; Crowe, Francesca L; Overvad, Kim; Sonestedt, Emily; Mattiello, Amalia; Peeters, Petra H; Wennberg, Maria; Jansson, Jan Håkan; Boutron-Ruault, Marie-Christine; Dossus, Laure; Dartois, Laureen; Li, Kuanrong; Barricarte, Aurelio; Ward, Heather; Riboli, Elio; Agnoli, Claudia; Huerta, José María; Sánchez, María-José; Tumino, Rosario; Altzibar, Jone M; Vineis, Paolo; Masala, Giovanna; Ferrari, Pietro; Muller, David C; Johansson, Mattias; Luisa Redondo, M; Tjønneland, Anne; Olsen, Anja; Olsen, Karina Standahl; Brustad, Magritt; Skeie, Guri; Lund, Eiliv

    2015-01-01

    Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046). PMID:25377533

  12. Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort.

    PubMed

    Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; Graff, Caroline; Thonberg, Håkan; Chiang, Huei-Hsin; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Nacmias, Benedetta; Sorbi, Sandro; Sanchez-Valle, Raquel; Lladó, Albert; Gelpi, Ellen; Almeida, Maria Rosário; Santana, Isabel; Tsolaki, Magda; Koutroumani, Maria; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matej, Radoslav; Rohan, Zdenek; Vandenbulcke, Mathieu; Vandenberghe, Rik; De Deyn, Peter P; Cras, Patrick; van der Zee, Julie; Sleegers, Kristel; Van Broeckhoven, Christine

    2015-12-01

    Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated. PMID:26411346

  13. Trend in Obesity Prevalence in European Adult Cohort Populations during Follow-up since 1996 and Their Predictions to 2015

    PubMed Central

    von Ruesten, Anne; Steffen, Annika; Floegel, Anna; van der A, Daphne L.; Masala, Giovanna; Tjønneland, Anne; Halkjaer, Jytte; Palli, Domenico; Wareham, Nicholas J.; Loos, Ruth J. F.; Sørensen, Thorkild I. A.; Boeing, Heiner

    2011-01-01

    Objective To investigate trends in obesity prevalence in recent years and to predict the obesity prevalence in 2015 in European populations. Methods Data of 97 942 participants from seven cohorts involved in the European Prospective Investigation into Cancer and Nutrition (EPIC) study participating in the Diogenes project (named as “Diogenes cohort” in the following) with weight measurements at baseline and follow-up were used to predict future obesity prevalence with logistic linear and non-linear (leveling off) regression models. In addition, linear and leveling off models were fitted to the EPIC-Potsdam dataset with five weight measures during the observation period to find out which of these two models might provide the more realistic prediction. Results During a mean follow-up period of 6 years, the obesity prevalence in the Diogenes cohort increased from 13% to 17%. The linear prediction model predicted an overall obesity prevalence of about 30% in 2015, whereas the leveling off model predicted a prevalence of about 20%. In the EPIC-Potsdam cohort, the shape of obesity trend favors a leveling off model among men (R2 = 0.98), and a linear model among women (R2 = 0.99). Conclusion Our data show an increase in obesity prevalence since the 1990ies, and predictions by 2015 suggests a sizeable further increase in European populations. However, the estimates from the leveling off model were considerably lower. PMID:22102897

  14. Binge Drinking and Psychoactive Drug Use In A Cohort of European Youths

    PubMed Central

    Siliquini, Roberta; Colombo, Alessandra; Berchialla, Paola; Bert, Fabrizio

    2012-01-01

    Background TEN-D by Night is an international, multicentre, cross-sectional portal survey conducted on a large sample of young people in six European countries. This paper aims to investigate the alcohol and psychoactive drug consumption of this sample, with a focus on the prevalence of binge drinking and the poly-drug habits of the TEN-D cohort. Design and Methods The study population consisted of 4695 young people attending recreational sites on weekend nights. The intervention included two questionnaires and two psychoactive substance detection tests performed at the entry and exit of the recreational sites. A multivariate logistic regression model was used to predict the probability of binge drinking. Results Binge drinking was reported by 20% of the males and 13% of the females (P=0.001) before entry into the recreational sites and by 18% of the males and 11% of the females before entry into the clubs (P<0.001). Poly-drug use was reported by 71% of the males and 66% of the females. Living with a parent (OR 1.57; P=0.01), seeking employment (OR 1.66; P=0.005) and cannabis consumption (several times per month and several times per week, OR 1.94 and 3.66, respectively, P<0.05) were associated with binge drinking. Conclusions Our survey showed that it is possible to identify individuals and groups at higher risk of binge drinking. This identification would allow for a focus on specific targets and would facilitate the redesign of prevention programmes. The increased use of psychoactive substances among youths should be studied extensively to promote successful prevention campaigns. PMID:25170451

  15. European Project on Osteoarthritis (EPOSA): methodological challenges in harmonization of existing data from five European population-based cohorts on aging

    PubMed Central

    2011-01-01

    Background The European Project on OSteoArthritis (EPOSA), here presented for the first time, is a collaborative study involving five European cohort studies on aging. This project focuses on the personal and societal burden and its determinants of osteoarthritis (OA). The aim of the current report is to describe the purpose of the project, the post harmonization of the cross-national data and methodological challenges related to the harmonization process Methods The study includes data from cohort studies in five European countries (Germany, Italy, the Netherlands, Spain and the United Kingdom) on older community-dwelling persons aged ≥ 59 years. The study design and main characteristics of the five cohort studies are described. Post harmonization algorithms are developed by finding a "common denominator" to merge the datasets and weights are calculated to adjust for differences in age and sex distribution across the datasets. Results A harmonized database was developed, consisting of merged data from all participating countries. In total, 10107 persons are included in the harmonized dataset with a mean age of 72.8 years (SD 6.1). The female/male ratio is 53.3/46.7%. Some variables were difficult to harmonize due to differences in wording and categories, differences in classifications and absence of data in some countries. The post harmonization algorithms are described in detail in harmonization guidelines attached to this paper. Conclusions There was little evidence of agreement on the use of several core data collection instruments, in particular on the measurement of OA. The heterogeneity of OA definitions hampers comparing prevalence rates of OA, but other research questions can be investigated using high quality harmonized data. By publishing the harmonization guidelines, insight is given into (the interpretation of) all post harmonized data of the EPOSA study. PMID:22122831

  16. European project on osteoarthritis: design of a six-cohort study on the personal and societal burden of osteoarthritis in an older European population

    PubMed Central

    2013-01-01

    Background Osteoarthritis (OA), the most common form of arthritis, is a major contributor to functional impairment and loss of independence in older persons. The European Project on OSteoArthritis (EPOSA) is a collaborative study involving six European cohort studies on ageing. This project focuses on the personal and societal burden and its determinants of osteoarthritis. This paper describes the design of the project, and presents some descriptive analyses on selected variables across countries. Methods/design EPOSA is an observational study including pre-harmonized data from European cohort studies (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) on older community-dwelling persons aged 65 to 85 years. In total, 2942 persons were included in the baseline study with a mean age of 74.2 years (SD 5.1), just over half were women (51,9%). The baseline assessment was conducted by a face-to-face interview followed by a clinical examination. Measures included physical, cognitive, psychological and social functioning, lifestyle behaviour, physical environment, wellbeing and care utilisation. The clinical examination included anthropometry, muscle strength, physical performance and OA exam. A follow-up assessment was performed 12–18 months after baseline. Discussion The EPOSA study is the first population-based study including a clinical examination of OA, using pre-harmonized data across European countries. The EPOSA study provides a unique opportunity to study the determinants and consequences of OA in general populations of older persons, including both care-seeking and non care-seeking persons. PMID:23597054

  17. Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study

    PubMed Central

    Bamia, C; Lagiou, P; Jenab, M; Aleksandrova, K; Fedirko, V; Trichopoulos, D; Overvad, K; Tjønneland, A; Olsen, A; Clavel-Chapelon, F; Boutron-Ruault, M-C; Kvaskoff, M; Katzke, V A; Kühn, T; Boeing, H; Nöthlings, U; Palli, D; Sieri, S; Panico, S; Tumino, R; Naccarati, A; Bueno-de-Mesquita, HB(as); Peeters, P H M; Weiderpass, E; Skeie, G; Quirós, J R; Agudo, A; Chirlaque, M-D; Sanchez, M-J; Ardanaz, E; Dorronsoro, M; Ericson, U; Nilsson, L M; Wennberg, M; Khaw, K-T; Wareham, N; Key, T J; Travis, R C; Ferrari, P; Stepien, M; Duarte-Salles, T; Norat, T; Murphy, N; Riboli, E; Trichopoulou, A

    2015-01-01

    Background: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case–control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d−1 increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d−1 increment): 0.83; 95% CI: 0.71–0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d−1 increment): 1.01; 95% CI: 0.92–1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease. PMID:25742480

  18. Multi-Center Traffic Management Advisor Operational Field Test Results

    NASA Technical Reports Server (NTRS)

    Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

    2005-01-01

    The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

  19. Composite Selection Signals for Complex Traits Exemplified Through Bovine Stature Using Multibreed Cohorts of European and African Bos taurus

    PubMed Central

    Randhawa, Imtiaz A. S.; Khatkar, Mehar S.; Thomson, Peter C.; Raadsma, Herman W.

    2015-01-01

    Understanding the evolution and molecular architecture of complex traits is important in domestic animals. Due to phenotypic selection, genomic regions develop unique patterns of genetic diversity called signatures of selection, which are challenging to detect, especially for complex polygenic traits. In this study, we applied the composite selection signals (CSS) method to investigate evidence of positive selection in a complex polygenic trait by examining stature in phenotypically diverse cattle comprising 47 European and 8 African Bos taurus breeds, utilizing a panel of 38,033 SNPs genotyped on 1106 animals. CSS were computed for phenotypic contrasts between multibreed cohorts of cattle by classifying the breeds according to their documented wither height to detect the candidate regions under selection. Using the CSS method, clusters of signatures of selection were detected at 26 regions (9 in European and 17 in African cohorts) on 13 bovine autosomes. Using comparative mapping information on human height, 30 candidate genes mapped at 12 selection regions (on 8 autosomes) could be linked to bovine stature diversity. Of these 12 candidate gene regions, three contained known genes (i.e., NCAPG-LCORL, FBP2-PTCH1, and PLAG1-CHCHD7) related to bovine stature, and nine were not previously described in cattle (five in European and four in African cohorts). Overall, this study demonstrates the utility of CSS coupled with strategies of combining multibreed datasets in the identification and discovery of genomic regions underlying complex traits. Characterization of multiple signatures of selection and their underlying candidate genes will elucidate the polygenic nature of stature across cattle breeds. PMID:25931611

  20. Air Pollution Exposure during Pregnancy and Childhood Autistic Traits in Four European Population-Based Cohort Studies: The ESCAPE Project

    PubMed Central

    Guxens, Mònica; Ghassabian, Akhgar; Gong, Tong; Garcia-Esteban, Raquel; Porta, Daniela; Giorgis-Allemand, Lise; Almqvist, Catarina; Aranbarri, Aritz; Beelen, Rob; Badaloni, Chiara; Cesaroni, Giulia; de Nazelle, Audrey; Estarlich, Marisa; Forastiere, Francesco; Forns, Joan; Gehring, Ulrike; Ibarluzea, Jesús; Jaddoe, Vincent W.V.; Korek, Michal; Lichtenstein, Paul; Nieuwenhuijsen, Mark J.; Rebagliato, Marisa; Slama, Rémy; Tiemeier, Henning; Verhulst, Frank C.; Volk, Heather E.; Pershagen, Göran; Brunekreef, Bert; Sunyer, Jordi

    2015-01-01

    Background Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. Objectives We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. Methods Ours was a collaborative study of four European population-based birth/child cohorts—CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. Results A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score. Conclusions Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies. Citation Guxens M, Ghassabian A, Gong T, Garcia-Esteban R, Porta D, Giorgis-Allemand L, Almqvist C, Aranbarri A, Beelen R, Badaloni C, Cesaroni G, de Nazelle A, Estarlich M, Forastiere F

  1. Has actuarial aging "slowed" over the past 250 years? A comparison of small-scale subsistence populations and European cohorts.

    PubMed

    Gurven, Michael; Fenelon, Andrew

    2009-04-01

    G.C. Williams's 1957 hypothesis famously argues that higher age-independent, or "extrinsic," mortality should select for faster rates of senescence. Long-lived species should therefore show relatively few deaths from extrinsic causes such as predation and starvation. Theoretical explorations and empirical tests of Williams's hypothesis have flourished in the past decade but it has not yet been tested empirically among humans. We test Williams's hypothesis using mortality data from subsistence populations and from historical cohorts from Sweden and England/Wales, and examine whether rates of actuarial aging declined over the past two centuries. We employ three aging measures: mortality rate doubling time (MRDT), Ricklefs's omega, and the slope of mortality hazard from ages 60-70, m'(60-70), and model mortality using both Weibull and Gompertz-Makeham hazard models. We find that (1) actuarial aging in subsistence societies is similar to that of early Europe, (2) actuarial senescence has slowed in later European cohorts, (3) reductions in extrinsic mortality associate with slower actuarial aging in longitudinal samples, and (4) men senesce more rapidly than women, especially in later cohorts. To interpret these results, we attempt to bridge population-based evolutionary analysis with individual-level proximate mechanisms. PMID:19220451

  2. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts

    PubMed Central

    Iszatt, Nina; Stigum, Hein; Verner, Marc-André; White, Richard A.; Govarts, Eva; Murinova, Lubica Palkovicova; Schoeters, Greet; Trnovec, Tomas; Legler, Juliette; Pelé, Fabienne; Botton, Jérémie; Chevrier, Cécile; Wittsiepe, Jürgen; Ranft, Ulrich; Vandentorren, Stéphanie; Kasper-Sonnenberg, Monika; Klümper, Claudia; Weisglas-Kuperus, Nynke; Polder, Anuschka

    2015-01-01

    Background Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels. Citation Iszatt N, Stigum H, Verner MA, White RA, Govarts E, Palkovicova Murinova L, Schoeters G, Trnovec T, Legler J, Pelé F, Botton J, Chevrier C, Wittsiepe J, Ranft U, Vandentorren S, Kasper-Sonnenberg M, Klümper C, Weisglas-Kuperus N, Polder A, Eggesbø M, OBELIX

  3. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.

    PubMed

    Molina-Montes, Esther; Sánchez, María-José; Zamora-Ros, Raul; Bueno-de-Mesquita, H B As; Wark, Petra A; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José-María; Barricarte, Aurelio; Quirós, José-Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay-Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie-Christine; Clavel-Chapelon, Françoise; Cross, Amanda J; Lu, Yunxia; Riboli, Elio; Duell, Eric J

    2016-10-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort. PMID:27184434

  4. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

    PubMed Central

    Molina‐Montes, Esther; Zamora‐Ros, Raul; Bueno‐de‐Mesquita, H.B(as); Wark, Petra A.; Obon‐Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C.; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José‐María; Barricarte, Aurelio; Quirós, José‐Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H.; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay‐Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun‐Rualt, Marie‐Christine; Clavel‐Chapelon, Françoise; Cross, Amanda J.; Lu, Yunxia; Riboli, Elio; Duell, Eric J.

    2016-01-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort. PMID:27184434

  5. Forming a Research Question from a Multi-Center Database

    PubMed Central

    Likosky, Donald S.

    2009-01-01

    Abstract: It is not uncommon for individuals to ask biostatisiticians and epidemiologists to assist them with a research project. Often the request is in the shape of statistical analyses. However, most of these requests are nothing more than missed opportunities. This manuscript focuses on the reasons underlying such a statement. Most individuals might say that the most important aspect of a study is its conclusion. Many who would disagree with this sentiment and would feel that the most important aspect of a study rather is the question it intends to address. If this question is not articulated sufficiently, any additional information stemming from the study will most likely be irrelevant. Herein, some principles for formulating (successfully) a question from a multi-center database will be described. PMID:19361039

  6. Mother's education and the risk of preterm and small for gestational age birth: a DRIVERS meta-analysis of 12 European cohorts

    PubMed Central

    Ruiz, Milagros; Goldblatt, Peter; Morrison, Joana; Kukla, Lubomír; Švancara, Jan; Riitta-Järvelin, Marjo; Taanila, Anja; Saurel-Cubizolles, Marie-Josèphe; Lioret, Sandrine; Bakoula, Chryssa; Veltsista, Alexandra; Porta, Daniela; Forastiere, Francesco; van Eijsden, Manon; Vrijkotte, Tanja G M; Eggesbø, Merete; White, Richard A; Barros, Henrique; Correia, Sofia; Vrijheid, Martine; Torrent, Maties; Rebagliato, Marisa; Larrañaga, Isabel; Ludvigsson, Johnny; Olsen Faresjö, Åshild; Hryhorczuk, Daniel; Antipkin, Youriy; Marmot, Michael; Pikhart, Hynek

    2015-01-01

    Background A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries. Methods Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts. Results Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied. Conclusions This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe. PMID:25911693

  7. Air Pollution and Respiratory Infections during Early Childhood: An Analysis of 10 European Birth Cohorts within the ESCAPE Project

    PubMed Central

    MacIntyre, Elaina A.; Gehring, Ulrike; Mölter, Anna; Fuertes, Elaine; Klümper, Claudia; Krämer, Ursula; Quass, Ulrich; Hoffmann, Barbara; Gascon, Mireia; Brunekreef, Bert; Koppelman, Gerard H.; Beelen, Rob; Hoek, Gerard; Birk, Matthias; de Jongste, Johan C.; Smit, H.A.; Cyrys, Josef; Gruzieva, Olena; Korek, Michal; Bergström, Anna; Agius, Raymond M.; de Vocht, Frank; Simpson, Angela; Porta, Daniela; Forastiere, Francesco; Badaloni, Chiara; Cesaroni, Giulia; Esplugues, Ana; Fernández-Somoano, Ana; Lerxundi, Aitana; Sunyer, Jordi; Cirach, Marta; Nieuwenhuijsen, Mark J.; Pershagen, Göran

    2013-01-01

    Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis. Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3). Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media. Citation: MacIntyre EA, Gehring U, Mölter A, Fuertes E, Klümper C, Krämer U, Quass U, Hoffmann B, Gascon M, Brunekreef B, Koppelman GH, Beelen R, Hoek G

  8. Dietary intake of acrylamide and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

    PubMed Central

    Obón-Santacana, Mireia; Peeters, Petra H.M.; Freisling, Heinz; Dossus, Laure; Clavel-Chapelon, Françoise; Baglietto, Laura; Schock, Helena; Fortner, Renée T.; Boeing, Heiner; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Menéndez, Virginia; Sanchez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Merritt, Melissa A.; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Orfanos, Philippos; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H.B.; Onland-Moret, N. Charlotte; Wirfält, Elisabeth; Stocks, Tanja; Idahl, Annika; Lundin, Eva; Skeie, Guri; Gram, Inger T.; Weiderpass, Elisabete; Riboli, Elio; Duell, Eric J

    2014-01-01

    Acrylamide, classified in 1994 by IARC as ‘probably carcinogenic’ to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results, and could not further examine histological subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) sub-cohort of women (n=325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method, and was evaluated both as a continuous variable (per 10μg/day) and in quintiles; when subgroups by histological EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 μg/day. No associations, and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10μg/day:1.02, 95%CI:0.96-1.09; HRQ5vsQ1:0.97, 95%CI:0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed. PMID:25300475

  9. Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes

    PubMed Central

    Jakaitiene, A; Aksenov, MO; Aksenova, AV; Druzhevskaya, AM; Astratenkova, IV; Egorova, ES; Gabdrakhmanova, LJ; Tubelis, L; Kucinskas, V; Utkus, A

    2016-01-01

    The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes’ status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups – weightlifters (87), powerlifters (60), throwers (14); by elite status – ‘elite’ (104), ‘sub-elite’ (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the ‘preferable genotype’ for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls. PMID:27601773

  10. Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes.

    PubMed

    Gineviciene, V; Jakaitiene, A; Aksenov, M O; Aksenova, A V; Druzhevskaya, A M; Astratenkova, I V; Egorova, E S; Gabdrakhmanova, L J; Tubelis, L; Kucinskas, V; Utkus, A

    2016-09-01

    The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes' status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups - weightlifters (87), powerlifters (60), throwers (14); by elite status - 'elite' (104), 'sub-elite' (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the 'preferable genotype' for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls. PMID:27601773

  11. Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study.

    PubMed

    Bamia, Christina; Lagiou, Pagona; Jenab, Mazda; Trichopoulou, Antonia; Fedirko, Veronika; Aleksandrova, Krasimira; Pischon, Tobias; Overvad, Kim; Olsen, Anja; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Racine, Antoine; Kuhn, Tilman; Boeing, Heiner; Floegel, Anna; Benetou, Vasiliki; Palli, Domenico; Grioni, Sara; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H B; Dik, Vincent K; Bhoo-Pathy, Nirmala; Uiterwaal, Cuno S P M; Weiderpass, Elisabete; Lund, Eiliv; Quirós, J Ramón; Zamora-Ros, Raul; Molina-Montes, Esther; Chirlaque, Maria-Dolores; Ardanaz, Eva; Dorronsoro, Miren; Lindkvist, Björn; Wallström, Peter; Nilsson, Lena Maria; Sund, Malin; Khaw, Kay-Tee; Wareham, Nick; Bradbury, Kathryn E; Travis, Ruth C; Ferrari, Pietro; Duarte-Salles, Talita; Stepien, Magdalena; Gunter, Marc; Murphy, Neil; Riboli, Elio; Trichopoulos, Dimitrios

    2015-04-15

    Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects. PMID:25219573

  12. The Multi-Center Airborne Coherent Atmospheric Wind Sensor, MACAWS

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1997-01-01

    In 1992 the atmospheric lidar remote sensing groups of the NASA Marshall Space Flight Center, NOAA Environmental Technology Laboratory, and Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor, MACAWS, which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in the troposphere and lower stratosphere. A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise which were developed for previous atmospheric research by the respective institutions. The motivation for the MACAWS program Is three-fold: to obtain fundamental measurements of sub-synoptic scale processes and features which may be used as a basis to improve sub-grid scale parameterizations in large-scale models; to obtain similar datasets in order to improve the understanding and predictive capabilities on the mesoscale; and to validate (simulate) the performance of existing (planned) satellite-borne sensors. Examples of the latter include participation in the validation of the NASA Scatterometer and the assessment of prospective satellite Doppler lidar for global tropospheric wind measurement. Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  13. Computer Assisted Multi-Center Creation of Medical Knowledge Bases

    PubMed Central

    Giuse, Nunzia Bettinsoli; Giuse, Dario A.; Miller, Randolph A.

    1988-01-01

    Computer programs which support different aspects of medical care have been developed in recent years. Their capabilities range from diagnosis to medical imaging, and include hospital management systems and therapy prescription. In spite of their diversity these systems have one commonality: their reliance on a large body of medical knowledge in computer-readable form. This knowledge enables such programs to draw inferences, validate hypotheses, and in general to perform their intended task. As has been clear to developers of such systems, however, the creation and maintenance of medical knowledge bases are very expensive. Practical and economical difficulties encountered during this long-term process have discouraged most attempts. This paper discusses knowledge base creation and maintenance, with special emphasis on medical applications. We first describe the methods currently used and their limitations. We then present our recent work on developing tools and methodologies which will assist in the process of creating a medical knowledge base. We focus, in particular, on the possibility of multi-center creation of the knowledge base.

  14. Development and validation of a predictive mortality risk score from a European hemodialysis cohort

    PubMed Central

    Floege, Jürgen; Gillespie, Iain A; Kronenberg, Florian; Anker, Stefan D; Gioni, Ioanna; Richards, Sharon; Pisoni, Ronald L; Robinson, Bruce M; Marcelli, Daniele; Froissart, Marc; Eckardt, Kai-Uwe

    2015-01-01

    Although mortality risk scores for chronic hemodialysis (HD) patients should have an important role in clinical decision-making, those currently available have limited applicability, robustness, and generalizability. Here we applied a modified Framingham Heart Study approach to derive 1- and 2-year all-cause mortality risk scores using a 11,508 European incident HD patient database (AROii) recruited between 2007 and 2009. This scoring model was validated externally using similar-sized Dialysis Outcomes and Practice Patterns Survey (DOPPS) data. For AROii, the observed 1- and 2-year mortality rates were 13.0 (95% confidence interval (CI; 12.3–13.8)) and 11.2 (10.4–12.1)/100 patient years, respectively. Increasing age, low body mass index, history of cardiovascular disease or cancer, and use of a vascular access catheter during baseline were consistent predictors of mortality. Among baseline laboratory markers, hemoglobin, ferritin, C-reactive protein, serum albumin, and creatinine predicted death within 1 and 2 years. When applied to the DOPPS population, the predictive risk score models were highly discriminatory, and generalizability remained high when restricted by incidence/prevalence and geographic location (C-statistics 0.68–0.79). This new model offers improved predictive power over age/comorbidity-based models and also predicted early mortality (C-statistic 0.71). Our new model delivers a robust and reproducible mortality risk score, based on readily available clinical and laboratory data. PMID:25651366

  15. Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: a population-based cohort study

    PubMed Central

    2014-01-01

    Background To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far. Methods Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008. Results With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins. Conclusions Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent. PMID:24997585

  16. Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

    PubMed Central

    Obón-Santacana, M; Kaaks, R; Slimani, N; Lujan-Barroso, L; Freisling, H; Ferrari, P; Dossus, L; Chabbert-Buffet, N; Baglietto, L; Fortner, R T; Boeing, H; Tjønneland, A; Olsen, A; Overvad, K; Menéndez, V; Molina-Montes, E; Larrañaga, N; Chirlaque, M-D; Ardanaz, E; Khaw, K-T; Wareham, N; Travis, R C; Lu, Y; Merritt, M A; Trichopoulou, A; Benetou, V; Trichopoulos, D; Saieva, C; Sieri, S; Tumino, R; Sacerdote, C; Galasso, R; Bueno-de-Mesquita, H B; Wirfält, E; Ericson, U; Idahl, A; Ohlson, N; Skeie, G; Gram, I T; Weiderpass, E; Onland-Moret, N C; Riboli, E; Duell, E J

    2014-01-01

    Background: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. Methods: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. Results: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). Conclusions: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers. PMID:24937665

  17. Managing Multi-center Flow Cytometry Data for Immune Monitoring.

    PubMed

    White, Scott; Laske, Karoline; Welters, Marij Jp; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21-23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables automated

  18. The Multi-center Airborne Coherent Atmospheric Wind Sensor.

    NASA Astrophysics Data System (ADS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James N.; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1998-04-01

    In 1992 the atmospheric lidar remote sensing groups of the National Aeronautics and Space Administration Marshall Space Flight Center, the National Oceanic and Atmospheric Administration/Environmental Technology Laboratory (NOAA/ETL), and the Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in three-dimensional volumes in the troposphere and lower stratosphere.A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise that were developed for previous atmospheric research by the respective institutions. For example, the laser transmitter is that of the mobile ground-based Doppler lidar system developed and used in atmospheric research for more than a decade at NOAA/ETL.The motivation for MACAWS is threefold: 1) to obtain fundamental measurements of subsynoptic-scale processes and features to improve subgrid-scale parameterizations in large-scale models, 2) to obtain datasets in order to improve the understanding of and predictive capabilities for meteorological systems on subsynoptic scales, and 3) to validate (simulate) the performance of existing (planned) satellite-borne sensors.Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following system improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  19. Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

    NASA Astrophysics Data System (ADS)

    Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; McCaul, E. W., Jr.

    1993-01-01

    This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall

  20. Managing Multi-center Flow Cytometry Data for Immune Monitoring

    PubMed Central

    White, Scott; Laske, Karoline; Welters, Marij JP; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1–5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21–23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables

  1. Depression and Wish to Die in a Multi-Center Cohort of ALS Patients

    PubMed Central

    Rabkin, Judith G.; Goetz, Raymond; Factor-Litvak, Pam; Hupf, Jonathan; McElhiney, Martin; Singleton, Jessica; Mitsumoto, Hiroshi

    2015-01-01

    Objective To determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multi-site study of patients with ALS. Methods Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Results Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329)had minor depression, and 5% (16/329)had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R ( p = .004) and gross motor function (p<.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p<.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. Conclusions Depressive disorders are not only to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such. PMID:25482273

  2. Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study

    PubMed Central

    Michaud, Dominique S.; Gallo, Valentina; Schlehofer, Brigitte; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Dahm, Christina C.; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Bamia, Christina; Kyrozis, Andreas; Sacerdote, Carlotta; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Mattiello, Amalia; Bueno-de-Mesquita, H. Bas; Ros, Martine M.; Peeters, Petra H. M.; van Gils, Carla H.; Lund, Eiliv; Bakken, Kjersti; Gram, Inger T.; Barricarte, Aurelio; Navarro, Carmen; Dorronsoro, Miren; Sánchez, Maria José; Rodríguez, Laudina; Duell, Eric J; Hallmans, Göran; Melin, Beatrice S.; Manjer, Jonas; Borgquist, Signe; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Tsilidis, Konstantinos K.; Romieu, Isabelle; Rinaldi, Sabina; Vineis, Paolo; Riboli, Elio

    2010-01-01

    Background The aetiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (CI). Results No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR = 1.62, 95% CI = 1.04-2.54) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR = 3.61, 95% CI = 1.75-7.46). Conclusion Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, appears to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. PMID:20802020

  3. Healthy Lifestyle and Risk of Cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study

    PubMed Central

    McKenzie, Fiona; Biessy, Carine; Ferrari, Pietro; Freisling, Heinz; Rinaldi, Sabina; Chajès, Veronique; Dahm, Christina C.; Overvad, Kim; Dossus, Laure; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Bueno-de-Mesquita, H. Bas; May, Anne; Peeters, Petra H.; Weiderpass, Elisabete; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Ericson, Ulrika; Wirfält, Elisabet; Travis, Ruth C.; Romieu, Isabelle

    2016-01-01

    Abstract It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors. This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models. There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41% and 33% for alcohol-related, 49% and 46% for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers. Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men. PMID:27100409

  4. Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

    PubMed

    Turney, Benjamin W; Appleby, Paul N; Reynard, John M; Noble, Jeremy G; Key, Timothy J; Allen, Naomi E

    2014-05-01

    The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation. PMID:24752465

  5. Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    PubMed

    Kyrø, Cecilie; Zamora-Ros, Raul; Scalbert, Augustin; Tjønneland, Anne; Dossus, Laure; Johansen, Christoffer; Bidstrup, Pernille Envold; Weiderpass, Elisabete; Christensen, Jane; Ward, Heather; Aune, Dagfinn; Riboli, Elio; His, Mathilde; Clavel-Chapelon, Françoise; Baglietto, Laura; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Overvad, Kim; Lasheras, Cristina; Travier, Noémie; Sánchez, Maria-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Perez-Cornago, Aurora; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Grioni, Sara; Berrino, Franco; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Peeters, Petra H; van Gils, Carla; Borgquist, Signe; Butt, Salma; Zeleniuch-Jacquotte, Anne; Sund, Malin; Hjartåker, Anette; Skeie, Guri; Olsen, Anja; Romieu, Isabelle

    2015-11-01

    The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status. PMID:26531755

  6. Healthy Lifestyle and Risk of Cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study.

    PubMed

    McKenzie, Fiona; Biessy, Carine; Ferrari, Pietro; Freisling, Heinz; Rinaldi, Sabina; Chajès, Veronique; Dahm, Christina C; Overvad, Kim; Dossus, Laure; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Bueno-de-Mesquita, H Bas; May, Anne; Peeters, Petra H; Weiderpass, Elisabete; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Ericson, Ulrika; Wirfält, Elisabet; Travis, Ruth C; Romieu, Isabelle

    2016-04-01

    It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors. This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models. There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41% and 33% for alcohol-related, 49% and 46% for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers. Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men. PMID:27100409

  7. Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort.

    PubMed

    Toulopoulou, T; van Haren, N; Zhang, X; Sham, P C; Cherny, S S; Campbell, D D; Picchioni, M; Murray, R; Boomsma, D I; Hulshoff Pol, H E; Pol, H H; Brouwer, R; Schnack, H; Fañanás, L; Sauer, H; Nenadic, I; Weisbrod, M; Cannon, T D; Kahn, R S

    2015-11-01

    In aetiologically complex illnesses such as schizophrenia, there is no direct link between genotype and phenotype. Intermediate phenotypes could help clarify the underlying biology and assist in the hunt for genetic vulnerability variants. We have previously shown that cognition shares substantial genetic variance with schizophrenia; however, it is unknown if this reflects pleiotropic effects, direct causality or some shared third factor that links both, for example, brain volume (BV) changes. We quantified the degree of net genetic overlap and tested the direction of causation between schizophrenia liability, brain structure and cognition in a pan-European schizophrenia twin cohort consisting of 1243 members from 626 pairs. Cognitive deficits lie upstream of the liability for schizophrenia with about a quarter of the variance in liability to schizophrenia explained by variation in cognitive function. BV changes lay downstream of schizophrenia liability, with 4% of BV variation explained directly by variation in liability. However, our power to determine the nature of the relationship between BV deviation and schizophrenia liability was more limited. Thus, while there was strong evidence that cognitive impairment is causal to schizophrenia liability, we are not in a position to make a similar statement about the relationship between liability and BV. This is the first study to demonstrate that schizophrenia liability is expressed partially through cognitive deficits. One prediction of the finding that BV changes lie downstream of the disease liability is that the risk loci that influence schizophrenia liability will thereafter influence BV and to a lesser extent. By way of contrast, cognitive function lies upstream of schizophrenia, thus the relevant loci will actually have a larger effect size on cognitive function than on schizophrenia. These are testable predictions. PMID:25450228

  8. Dietary intake of acrylamide and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort.

    PubMed

    Obón-Santacana, Mireia; Peeters, Petra H M; Freisling, Heinz; Dossus, Laure; Clavel-Chapelon, Françoise; Baglietto, Laura; Schock, Helena; Fortner, Renée T; Boeing, Heiner; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Menéndez, Virginia; Sanchez, Maria-José; Larrañaga, Nerea; Huerta Castaño, José María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Merritt, Melissa A; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Orfanos, Philippos; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H B; Onland-Moret, N Charlotte; Wirfält, Elisabeth; Stocks, Tanja; Idahl, Annika; Lundin, Eva; Skeie, Guri; Gram, Inger T; Weiderpass, Elisabete; Riboli, Elio; Duell, Eric J

    2015-01-01

    Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 μg/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 μg/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10μg/d,1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed. PMID:25300475

  9. Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone

    PubMed Central

    Swerdlow, Anthony J; Cooke, Rosi; Albertsson-Wikland, Kersti; Borgström, Birgi; Butler, Gar; Cianfarani, Stefan; Clayton, Pete; Coste, Joë; Deodati, Annalis; Ecosse, Emmanue; Gausche, Rut; Giacomozzi, Claudi; Kiess, Wielan; Hokken-Koelega, Anita C.S; Kuehni, Claudia E; Landier, Fabienn; Maes, Mar; Mullis, Primus-E; Pfaffle, Rolan; Sävendahl, Lar; Sommer, Gri; Thomas, Murie; Tollerfield, Sall; Zandwijken, Gladys R.J; Carel, Jean-Claud

    2015-01-01

    Background The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. Patients and Methods: The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. Conclusion The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country. PMID:26227295

  10. Regional Gray Matter Atrophy in Relapsing Remitting Multiple Sclerosis: Baseline Analysis of Multi-Center Data

    PubMed Central

    Datta, Sushmita; Staewen, Terrell D.; Cofield, Stacy S.; Cutter, Gary R.; Lublin, Fred D.; Wolinsky, Jerry S.; Narayana, Ponnada A.

    2015-01-01

    Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson’s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r = −0.133; p < 0.001) and DD (r = −0.098; p = 0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r = −0.492; p-value < 0.001), T1 LL (r = −0.473; p-value < 0.001) and nCSF (r = −0.367; p-value < 0.001). PMID:25787188

  11. Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data.

    PubMed

    Datta, Sushmita; Staewen, Terrell D; Cofield, Stacy S; Cutter, Gary R; Lublin, Fred D; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-03-01

    Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson׳s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r=-0.133; p<0.001) and DD (r=-0.098; p=0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r=-0.492; P-value<0.001), T1 LL (r=-0.473; P-value<0.001) and nCSF (r=-0.367; P-value<0.001). PMID:25787188

  12. Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study

    PubMed Central

    2011-01-01

    Background Dengue re-emerges in Singapore despite decades of effective vector control; the infection predominantly afflicts adults. Severe dengue not fulfilling dengue hemorrhagic fever (DHF) criteria according to World Health Organization (WHO) 1997 guideline was increasingly reported. A new WHO 2009 guideline emphasized warning signs and a wider range of severe dengue manifestations. We aim to evaluate the utility of these two guidelines in confirmed adult dengue fatalities. Methods We conducted a multi-center retrospective chart review of all confirmed adult dengue deaths in Singapore from 1 January 2004 to 31 December 2008. Results Of 28 adult dengue deaths, median age was 59 years. Male gender comprised 67.9% and co-morbidities existed in 75%. From illness onset, patients presented for admission at a median of 4 days and death occurred at a median of 12 days. Intensive care admission was required in 71.4%. Probable dengue was diagnosed in 32.1% by WHO 1997 criteria and 78.6% by WHO 2009. The earliest warning sign was persistent vomiting at a median of 1.5 days. Hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L was associated with the shortest interval to death at a median of 3 days. Only 35.7% of death cases fulfilled DHF criteria by WHO 1997 versus severe dengue in 100.0% by WHO 2009 criteria. Deaths were due to shock and organ failure. Acute renal impairment occurred in 71.4%, impaired consciousness 57.1% and severe hepatitis 53.6%. Conclusions In our adult fatal dengue cohort, WHO 2009 criteria had higher sensitivity in diagnosing probable dengue and severe dengue compared with WHO 1997. As warning signs, persistent vomiting occurred early and hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L preceded death most closely. PMID:21569427

  13. Multi-Center Electronic Structure Calculations for Plasma Equation of State

    SciTech Connect

    Wilson, B G; Johnson, D D; Alam, A

    2010-12-14

    We report on an approach for computing electronic structure utilizing solid-state multi-center scattering techniques, but generalized to finite temperatures to model plasmas. This approach has the advantage of handling mixtures at a fundamental level without the imposition of ad hoc continuum lowering models, and incorporates bonding and charge exchange, as well as multi-center effects in the calculation of the continuum density of states.

  14. Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries

    PubMed Central

    Heintjes, Edith M; Williams, Rachael; Hoti, Fabian; Christopher, Solomon; Majak, Maila; Kool-Houweling, Leanne; Strongman, Helen; Linder, Marie; Dolin, Paul; Bahmanyar, Shahram

    2016-01-01

    .26) in the nearest match cohort). Conclusions This study shows no evidence of an association between ever use of pioglitzone and risk of bladder cancer compared with never use, which is consistent with results from other recent studies that also included a long follow-up period. Trial registration Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626). PMID:27530399

  15. COBA-Cohort: a prospective cohort of HIV-negative men who have sex with men, attending community-based HIV testing services in five European countries (a study protocol)

    PubMed Central

    Fernàndez-López, Laura; Fuertes, Ricardo; Rojas Castro, Daniela; Pichon, François; Cigan, Bojan; Chanos, Sophocles; Meireles, Paula; Morel, Stéphane; Slaaen Kaye, Per; Agustí, Cristina; Klavs, Irena; Casabona, Jordi

    2016-01-01

    Introduction Community-based voluntary counselling and testing (CBVCT) services for men who have sex with men (MSM) can reach those most-at-risk and provide an environment for gay men that is likely to be non-stigmatising. Longitudinal data on the behaviour of HIV-negative MSM are scarce in Europe. The aim of this protocol, developed during the Euro HIV Early Diagnosis And Treatment (EDAT) project, is to implement a multicentre community-based cohort of HIV-negative MSM attending 15 CBVCT services in 5 European countries. Research objectives (1) To describe the patterns of CBVCT use, (2) to estimate HIV incidence, and to identify determinants of (3) HIV seroconversion and (4) HIV and/or sexually transmitted infection (STI) test-seeking behaviour. Methods and analysis All MSM aged 18 years or over and who had a negative HIV test result are invited to participate in the COmmunity-BAsed Cohort (COBA-Cohort). Study enrolment started in February 2015, and is due to continue for at least 12 months at each study site. Follow-up frequency depends on the testing recommendations in each country (at least 1 test per year). Sociodemographic data are collected at baseline; baseline and follow-up questionnaires both gather data on attitudes and perceptions, discrimination, HIV/STI testing history, sexual behaviour, condom use, and pre- and post-exposure prophylaxis. Descriptive, exploratory and multivariate analyses will be performed to address the main research objectives of this study, using appropriate statistical tests and models. These analyses will be performed on the whole cohort data and stratified by study site or country. Ethics and dissemination The study was approved by the Public Health authorities of each country where the study is being implemented. Findings from the COBA-Cohort study will be summarised in a report to the European Commission, and in leaflets to be distributed to study participants. Articles and conference abstracts will be submitted to peer

  16. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  17. European multi-center evaluation of the Abbott Cell-Dyn sapphire hematology analyzer.

    PubMed

    Müller, Robert; Mellors, Ian; Johannessen, Berit; Aarsand, Aasne K; Kiefer, Paul; Hardy, John; Kendall, Richard; Scott, Colin Stephen

    2006-01-01

    This study presents the results of performance evaluations of the Cell-Dyn Sapphire (CD-Sapphire) undertaken by 3 study sites in Europe. These studies focused on the routine blood count analyses with specific consideration of precision and imprecision, linearity, inter-instrument correlations, and white blood cell differential and flagging efficiencies. The CD-Sapphire was compared to the Cell-Dyn CD4000, Bayer Advia 120, Beckman Coulter GenS, and reference microscopy. PMID:16513543

  18. Has actuarial aging “slowed” over the past 250 years? A comparison of small-scale subsistence populations and European cohorts

    PubMed Central

    Gurven, Michael; Fenelon, Andrew

    2012-01-01

    G.C. Williams’ 1957 hypothesis famously argues that higher age-independent, or “extrinsic”, mortality should select for faster rates of senescence. Long-lived species should therefore show relatively few deaths from extrinsic causes such as predation and starvation. Theoretical explorations and empirical tests of Williams’ hypothesis have flourished in the past decade but it has not yet been tested empirically among humans. We test Williams’ hypothesis using mortality data from subsistence populations and from historical cohorts from Sweden and England/Wales, and examine whether rates of actuarial aging declined over the past two centuries. We employ three aging measures: mortality rate doubling time (MRDT), Ricklef’s ω, and the slope of mortality hazard from ages sixty to seventy, m’60–70, and model mortality using both Weibull and Gompertz-Makeham hazard models. We find that (1) actuarial aging in subsistence societies is similar to that of early Europe, (2) actuarial senescence has slowed in later European cohorts, (3) reductions in extrinsic mortality associate with slower actuarial aging in longitudinal samples, and (4) men senesce more rapidly than women, especially in later cohorts. To interpret these results, we attempt to bridge population-based evolutionary analysis with individual-level proximate mechanisms. PMID:19220451

  19. Health-related Quality of Life in Inflammatory Bowel Disease in a European-wide Population-based Cohort 10 Years After Diagnosis

    PubMed Central

    Høivik, Marte Lie; Langholz, Ebbe; Odes, Selwyn; Småstuen, Milada; Stockbrugger, Reinhold; Hoff, Geir; Moum, Bjørn; Bernklev, Tomm

    2015-01-01

    Background: Chronic inflammatory bowel disease (IBD) negatively affects the patient's health-related quality of life (HRQoL). Only a few population-based studies have compared the HRQoL of patients with the background population. The aim of this study was to evaluate the HRQoL in a European cohort of patients with ulcerative colitis and Crohn's disease 10 years after diagnosis (European Collaborative study group of Inflammatory Bowel Disease) compared with the national background population in each country and to assess possible country-specific differences. Methods: Patients with IBD from 7 European countries were invited to a follow-up visit 10 years after their diagnosis of IBD. We assessed their clinical and demographic data, including the generic HRQoL questionnaire short form health survey-36. Countrywise comparison with the background population was performed with z-scores using the Cohen's effect size index. Results: Seven hundred sixty-nine patients were eligible for the study. We registered statistically significant and clinically relevant decreases in the short form health survey-36 dimensional scores in patients with symptoms at the time of follow-up and for patients reporting sick leave during the previous year or having received disablement pension. In the Netherlands and Norway, there was a moderate difference between the patients with IBD and the background population for the general health dimension. Conclusions: Overall, the HRQoL was not reduced in the IBD cohort compared with the background populations. However, in addition to older age and female gender, current symptoms at follow-up, disablement pension, and sick leave during the previous year were significantly associated with a reduced HRQoL in patients with IBD. PMID:25569735

  20. Long-Term Exposure to Ambient Air Pollution and Incidence of Cerebrovascular Events: Results from 11 European Cohorts within the ESCAPE Project

    PubMed Central

    Cesaroni, Giulia; Peters, Annette; Andersen, Zorana J.; Badaloni, Chiara; Beelen, Rob; Caracciolo, Barbara; Cyrys, Josef; de Faire, Ulf; de Hoogh, Kees; Eriksen, Kirsten T.; Fratiglioni, Laura; Galassi, Claudia; Gigante, Bruna; Havulinna, Aki S.; Hennig, Frauke; Hilding, Agneta; Hoek, Gerard; Hoffmann, Barbara; Houthuijs, Danny; Korek, Michal; Lanki, Timo; Leander, Karin; Magnusson, Patrik K.; Meisinger, Christa; Migliore, Enrica; Overvad, Kim; Östenson, Claes-Göran; Pedersen, Nancy L.; Pekkanen, Juha; Penell, Johanna; Pershagen, Goran; Pundt, Noreen; Pyko, Andrei; Raaschou-Nielsen, Ole; Ranzi, Andrea; Ricceri, Fulvio; Sacerdote, Carlotta; Swart, Wim J.R.; Turunen, Anu W.; Vineis, Paolo; Weimar, Christian; Weinmayr, Gudrun; Wolf, Kathrin; Brunekreef, Bert; Forastiere, Francesco

    2014-01-01

    Background: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. Objectives: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. Methods: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ≤ 2.5 μm in diameter], coarse PM (PM between 2.5 and 10 μm), PM10 (PM ≤ 10 μm), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation. Results: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-μg/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ≥ 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 μg/m3 (HR = 1.33, 95% CI: 1.01, 1.77). Conclusions: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value. Citation: Stafoggia M, Cesaroni G, Peters A, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, Cyrys J, de Faire U, de Hoogh K, Eriksen KT, Fratiglioni L, Galassi C, Gigante B, Havulinna AS, Hennig F, Hilding A, Hoek G, Hoffmann B, Houthuijs D, Korek M, Lanki T, Leander K, Magnusson

  1. Open versus minimally invasive sacroiliac joint fusion: a multi-center comparison of perioperative measures and clinical outcomes

    PubMed Central

    2013-01-01

    Background Sacroiliac (SI) joint pain is an under diagnosed source of low back pain due in part to lack of visible pathology on radiographs and symptoms mimicking other back-related disorders. Open SI joint fusion has been performed since the 1920s. This technique has fallen out of favor with the introduction of minimally invasive options. To date there has been no direct comparison between open and MIS SI joint fusion. Methods We conducted a multi-center, retrospective comparative cohort study of patients who underwent SI joint fusion using either an open surgical (OS) technique using a combination of screws and cages or a minimally invasive surgical (MIS) technique with a series of titanium plasma spray (TPS) coated triangular implants. Operative measures including surgical operating time, length of hospitalization and estimated blood loss (EBL) were collected along with demographics and medical history, surgical complications, and 12- and 24-month pain scores. Improvements in pain were compared after matching for age and gender and controlling for a history of lumbar spine fusion using repeated measures analysis of variance. Results Data were available for 263 patients treated by 7 surgeons; 149 patients treated with OS and 114 treated with MIS SI joint fusion. Compared to OS patients, MIS patients were on average 10 years older (mean age 57 vs. 46) and 69% of all patients were female. MIS operative measures of EBL, operating time and length of hospitalization were significantly lower than open surgery (p < 0.001). Pain relief, measured as change from baseline to 12 months in VAS pain rating, was 3.5 points lower in the MIS vs. OS group (-6.2 vs. -2.7 points, p < 0.001). When matched for age, gender and a history of prior lumbar spinal fusion, postoperative pain scores were on average 3.0 points (95% CI 2.1 – 4.0) lower in MIS vs. OS (rANOVA p < 0.001). Conclusions In this multi-center comparative study, patients who underwent either OS or MIS SI

  2. Predictors, Neuroimaging Characteristics and Long-Term Outcome of Severe European Tick-Borne Encephalitis: A Prospective Cohort Study

    PubMed Central

    Lenhard, Thorsten; Ott, Daniela; Jakob, Nurith J.; Pham, Mirko; Bäumer, Philipp; Martinez-Torres, Francisco; Meyding-Lamadé, Uta

    2016-01-01

    Background and Objectives Tick-borne encephalitis (TBE) still represents a considerable medical and health economic problem in Europe and entails a potential threat to travellers. The aim of this study was to characterise the conditions of severe TBE by precisely recording its clinical variants, the related neuroimaging features, and the variant-specific long-term outcome and by identifying predictors for severe courses. Methods A cohort of 111 TBE patients (median age 51, range 17–75 years; 42% females) was analysed prospectively. Data were acquired from the department of neurology, University Hospital Heidelberg, and the infectious diseases registry of the Robert-Koch institute Berlin. Neurological status was ascertained by protocol at admission and discharge and the degree of disability was scored using the modified RANKIN Scale (mRS; clinical score addressing neurological disability, range from 0, healthy to 6, dead) at admission and at follow-up. Follow-up examination was conducted by means of a telephone interview. To identify independent predictors for severe TBE and functional outcome, modelled logistic regression was performed. MRI changes were correlated with infection variants. To assess alpha-motor neuron injury patterns, we used high-resolution magnetic resonance neurography (hrMRN). Analyses were performed at the Department of Neurology, University Hospital, University of Heidelberg from April 2004 through September 2014 Results Acute course: 3.6% of patients died during the acute infection. All patients with a lethal course suffered from meningoencephaloradiculitis (MER, 14.4% of the cohort), which is associated with a significantly higher risk of requiring intensive care (p = 0.004) and mechanical ventilation (p<0.001) than menigoencephalitis (ME, 27.9% of the cohort). At admission, both MER and ME groups were severely affected, with the MER group having a statistically higher mRS score (median of 5 in the MER groups versus 4 in the ME group; p<0

  3. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  4. Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

    NASA Technical Reports Server (NTRS)

    Landry, Steven J.; Farley, Todd; Hoang, Ty

    2005-01-01

    Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

  5. Cognitive ability, parental socioeconomic position and internalising and externalising problems in adolescence: Findings from two European cohort studies

    PubMed Central

    Araya, Ricardo; Lawlor, Debbie A.; Ormel, Johan; Verhulst, Frank C.; Oldehinkel, Albertine J.

    2010-01-01

    We investigated whether cognitive ability (CA) may be a moderator of the relationship of parental socioeconomic position (SEP) with internalising and externalising problems in adolescents. We used data from two longitudinal cohort studies; the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Tracking Adolescents’ Individual Lives Survey (TRAILS). Indicators of SEP were mother’s education and household income. CA was estimated with IQ scores, derived from the Wechsler Intelligence Scale for Children. Internalising and externalising problems were measured with the Strengths and Difficulties Questionnaire in ALSPAC and with the Child Behavior Checklist in TRAILS. Logistic regression analyses were used to estimate the relative index of inequality (RII) for each outcome; the RII provides the odds ratio comparing the most to least deprived for each measure of SEP. In fully adjusted models an association of mother’s education with externalising problems was observed [ALSPAC RII 1.42 (95%CI: 1.01–1.99); TRAILS RII 2.21 (95%CI: 1.37–3.54)], and of household income with internalising and externalising problems [pooled ALSPAC & TRAILS internalising RII 1.30 (95%CI: 0.99–1.71); pooled ALSPAC & TRAILS externalising RII 1.38 (95%CI: 1.03–1.84)]. No consistent associations were observed between mother’s education and internalising problems. Results of stratified analyses and interaction-terms showed no evidence that CA moderated the association of SEP with internalising or externalising problems. PMID:20535529

  6. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.

    PubMed

    Hughes, David J; Fedirko, Veronika; Jenab, Mazda; Schomburg, Lutz; Méplan, Catherine; Freisling, Heinz; Bueno-de-Mesquita, H B as; Hybsier, Sandra; Becker, Niels-Peter; Czuban, Magdalena; Tjønneland, Anne; Outzen, Malene; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadia; Kühn, Tilman; Kaaks, Rudolf; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Lagiou, Pagona; Panico, Salvatore; Peeters, Petra H; Weiderpass, Elisabete; Skeie, Guri; Dagrun, Engeset; Chirlaque, Maria-Dolores; Sánchez, Maria-Jose; Ardanaz, Eva; Ljuslinder, Ingrid; Wennberg, Maria; Bradbury, Kathryn E; Vineis, Paolo; Naccarati, Alessio; Palli, Domenico; Boeing, Heiner; Overvad, Kim; Dorronsoro, Miren; Jakszyn, Paula; Cross, Amanda J; Quirós, Jose Ramón; Stepien, Magdalena; Kong, So Yeon; Duarte-Salles, Talita; Riboli, Elio; Hesketh, John E

    2015-03-01

    Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (p(trend) = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (p(trend) = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (p(trend) = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (p(trend) = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women. PMID:25042282

  7. Pre-diagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

    PubMed Central

    Fedirko, Veronika; Riboli, Elio; Bueno-de-Mesquita, H. Bas; Rinaldi, Sabina; Pischon, Tobias; Norat, Teresa; Jansen, Eugène H.J.M.; van Duijnhoven, Fränzel J.B.; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Engel, Pierre; Kaaks, Rudolf; Teucher, Birgit; Boeing, Heiner; Buijsse, Brian; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Lagiou, Pagona; Sieri, Sabina; Vineis, Paolo; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; van Gils, Carla H; Peeters, Petra HM; Chirlaque, Maria-Dolores; Gurrea, Aurelio Barricarte; Rodríguez, Laudina; Molina-Montes, Esther; Dorronsoro, Miren; Bonet, Catalina; Palmqvist, Richard; Hallmans, Göran; Key, Timothy J.; Tsilidis, Konstantinos K; Khaw, Kay-Tee; Romieu, Isabelle; Straif, Kurt; Wark, Petra A.; Romaguera, Dora; Jenab, Mazda

    2011-01-01

    Background Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). Methods A case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating pre-diagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95%CI) for the association between circulating PTH and CRC risk. Results In multivariate analyses (including adjustment for 25(OH)D concentration) with a priori defined cut-points, high levels of serum PTH (≥65ng/L) compared to medium PTH levels of 30–65 ng/L were associated with increased CRC risk (RR=1.41, 95%CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95%CI: 1.14-2.75) and 1.15 (95%CI: 0.73-1.84) in men and women, respectively (Pheterogeneity=0.01). In sub-group analyses by anatomical sub-site, the risk for colon cancer was RR=1.56, 95%CI:1.03-2.34, and for rectal cancer RR=1.20, 95%CI:0.72-2.01 (Pheterogeneity=0.21). Effect modification by various risk factors was examined. Conclusions The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. Impact To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. PMID:21378267

  8. Polymicrogyria-associated epilepsy: a multi-center phenotypic study from the Epilepsy Phenome/Genome Project

    PubMed Central

    Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna

    2013-01-01

    Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890

  9. Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study.

    PubMed

    Lassale, Camille; Gunter, Marc J; Romaguera, Dora; Peelen, Linda M; Van der Schouw, Yvonne T; Beulens, Joline W J; Freisling, Heinz; Muller, David C; Ferrari, Pietro; Huybrechts, Inge; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Overvad, Kim; Dahm, Christina C; Olsen, Anja; Roswall, Nina; Tsilidis, Konstantinos K; Katzke, Verena A; Kühn, Tilman; Buijsse, Brian; Quirós, José-Ramón; Sánchez-Cantalejo, Emilio; Etxezarreta, Nerea; Huerta, José María; Barricarte, Aurelio; Bonet, Catalina; Khaw, Kay-Tee; Key, Timothy J; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Boer, Jolanda M A; Sonestedt, Emily; Nilsson, Lena Maria; Renström, Frida; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Moons, Karel G M; Riboli, Elio; Tzoulaki, Ioanna

    2016-01-01

    Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors. PMID:27409582

  10. Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study

    PubMed Central

    Lassale, Camille; Gunter, Marc J.; Romaguera, Dora; Peelen, Linda M.; Van der Schouw, Yvonne T.; Beulens, Joline W. J.; Freisling, Heinz; Muller, David C.; Ferrari, Pietro; Huybrechts, Inge; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Overvad, Kim; Dahm, Christina C.; Olsen, Anja; Roswall, Nina; Tsilidis, Konstantinos K.; Katzke, Verena A.; Kühn, Tilman; Buijsse, Brian; Quirós, José-Ramón; Sánchez-Cantalejo, Emilio; Etxezarreta, Nerea; Huerta, José María; Barricarte, Aurelio; Bonet, Catalina; Khaw, Kay-Tee; Key, Timothy J.; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Boer, Jolanda M. A.; Sonestedt, Emily; Nilsson, Lena Maria; Renström, Frida; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Moons, Karel G. M.; Riboli, Elio; Tzoulaki, Ioanna

    2016-01-01

    Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72–0.79) to 0.88 (0.84–0.92) for all-cause, 0.76 (0.69–0.83) to 0.84 (0.76–0.92) for CVD and 0.78 (0.73–0.83) to 0.91 (0.85–0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors. PMID:27409582

  11. Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database

    PubMed Central

    Ruffini, Enrico; Detterbeck, Frank; Van Raemdonck, Dirk; Rocco, Gaetano; Thomas, Pascal; Weder, Walter; Brunelli, Alessandro; Evangelista, Andrea; Venuta, Federico; Khaled, AlKattan; Arame, Alex; Refai, Majed; Casadio, Caterina; Carbognani, Paolo; Cerfolio, Robert; Donati, Giovanni; Foroulis, Christophoros N; Gebitekin, Cengiz; de Antonio, David Gomez; Kernstine, Kemp H; Keshavjee, Shaf; Moser, Bernhard; Lequaglie, Cosimo; Liberman, Moishe; Lim, Eric; Nicholson, Andrew G; Lang-Lazdunski, Loic; Mancuso, Maurizio; Altorki, Nasser; Nosotti, Mario; Novoa, Nuria M; Brioude, Geoffrey; Oliaro, Alberto; Filosso, Pier Luigi; Saita, Salvatore; Scarci, Marco; Schützner, Jan; Terzi, Alberto; Toker, Alper; Van Veer, Hans; Anile, Marco; Rendina, Erino; Voltolini, Luca; Zurek, Wojciech

    2014-01-01

    OBJECTIVES A retrospective database was developed by the European Society of Thoracic Surgeons, collecting patients submitted to surgery for thymic tumours to analyse clinico-pathological prognostic predictors. METHODS A total of 2151 incident cases from 35 institutions were collected from 1990 to 2010. Clinical-pathological characteristics were analysed, including age, gender, associated myasthenia gravis stage (Masaoka), World Health Organization histology, type of thymic tumour [thymoma, thymic carcinoma (TC), neuroendocrine thymic tumour (NETT)], type of resection (complete/incomplete), tumour size, adjuvant therapy and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival and the cumulative incidence of recurrence (CIR). RESULTS A total of 2030 patients were analysed for OS (1798 thymomas, 191 TCs and 41 NETTs). Ten-year OS was 0.73 (95% confidence interval 0.69–0.75). Complete resection (R0) was achieved in 88% of the patients. Ten-year CIR was 0.12 (0.10–0.15). Predictors of shorter OS were increased age (P < 0–001), stage [III vs I HR 2.66, 1.80–3.92; IV vs I hazard ratio (HR) 4.41, 2.67–7.26], TC (HR 2.39, 1.68–3.40) and NETT (HR 2.59, 1.35–4.99) vs thymomas and incomplete resection (HR 1.74, 1.18–2.57). Risk of recurrence increased with tumour size (P = 0.003), stage (III vs I HR 5.67, 2.80–11.45; IV vs I HR 13.08, 5.70–30.03) and NETT (HR 7.18, 3.48–14.82). Analysis using a propensity score indicates that the administration of adjuvant therapy was beneficial in increasing OS (HR 0.69, 0.49–0.97) in R0 resections. CONCLUSIONS Masaoka stages III–IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival. PMID:24482389

  12. Design and methods in a multi-center case-control interview study.

    PubMed Central

    Hartge, P; Cahill, J I; West, D; Hauck, M; Austin, D; Silverman, D; Hoover, R

    1984-01-01

    We conducted a case-control study in ten areas of the United States in which a total of 2,982 bladder cancer patients and 5,782 population controls were interviewed. We employed a variety of existing and new techniques to reduce bias and to monitor the quality of data collected. We review here many of the design elements and field methods that can be generally applied in epidemiologic studies, particularly multi-center interview studies, and explain the reasons for our selection of the methods, instruments, and procedures used. PMID:6689843

  13. ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians

    PubMed Central

    Voisin, Sarah; Guilherme, João Paulo F. L.; Yan, Xu; Pushkarev, Vladimir P.; Cieszczyk, Pawel; Massidda, Myosotis; Calò, Carla M.; Dyatlov, Dmitry A.; Kolupaev, Vitaliy A.; Pushkareva, Yuliya E.; Maciejewska, Agnieszka; Sawczuk, Marek; Lancha, Antonio H.; Artioli, Guilherme G.

    2016-01-01

    Skeletal muscle strength and mass, major contributors to sprint/power athletic performance, are influenced by genetics. However, to date, only a handful of genetic variants have been associated with sprint/power performance. The ACVR1B A allele (rs rs2854464) has previously been associated with increased muscle-strength in non-athletic cohort. However, no follow-up and/or replications studies have since been conducted. Therefore, the aim of the present study was to compare the genotype distribution of ACVR1B rs2854464 between endurance athletes (E), sprint/power (S/P) athletes, mixed athletes (M), and non-athletic control participants in 1672 athletes (endurance athletes, n = 482; sprint/power athletes, n = 578; mixed athletes, n = 498) and 1089 controls (C) of both European Caucasians (Italian, Polish and Russians) and Brazilians. We have also compared the genotype distribution according to the athlete’s level of competition (elite vs. sub-elite). DNA extraction and genotyping were performed using various methods. Fisher's exact test (adjusted for multiple comparisons) was used to test whether the genotype distribution of rs2854464 (AA, AG and GG) differs between groups. The A allele was overrepresented in S/P athletes compared with C in the Caucasian sample (adjusted p = 0.048), whereas there were no differences in genotype distribution between E athletes and C, in neither the Brazilian nor the Caucasian samples (adjusted p > 0.05). When comparing all Caucasian athletes regardless of their sporting discipline to C, we found that the A allele was overrepresented in athletes compared to C (adjusted p = 0.024). This association was even more pronounced when only elite-level athletes were considered (adjusted p = 0.00017). In conclusion, in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. This reinforces the

  14. ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians.

    PubMed

    Voisin, Sarah; Guilherme, João Paulo F L; Yan, Xu; Pushkarev, Vladimir P; Cieszczyk, Pawel; Massidda, Myosotis; Calò, Carla M; Dyatlov, Dmitry A; Kolupaev, Vitaliy A; Pushkareva, Yuliya E; Maciejewska, Agnieszka; Sawczuk, Marek; Lancha, Antonio H; Artioli, Guilherme G; Eynon, Nir

    2016-01-01

    Skeletal muscle strength and mass, major contributors to sprint/power athletic performance, are influenced by genetics. However, to date, only a handful of genetic variants have been associated with sprint/power performance. The ACVR1B A allele (rs rs2854464) has previously been associated with increased muscle-strength in non-athletic cohort. However, no follow-up and/or replications studies have since been conducted. Therefore, the aim of the present study was to compare the genotype distribution of ACVR1B rs2854464 between endurance athletes (E), sprint/power (S/P) athletes, mixed athletes (M), and non-athletic control participants in 1672 athletes (endurance athletes, n = 482; sprint/power athletes, n = 578; mixed athletes, n = 498) and 1089 controls (C) of both European Caucasians (Italian, Polish and Russians) and Brazilians. We have also compared the genotype distribution according to the athlete's level of competition (elite vs. sub-elite). DNA extraction and genotyping were performed using various methods. Fisher's exact test (adjusted for multiple comparisons) was used to test whether the genotype distribution of rs2854464 (AA, AG and GG) differs between groups. The A allele was overrepresented in S/P athletes compared with C in the Caucasian sample (adjusted p = 0.048), whereas there were no differences in genotype distribution between E athletes and C, in neither the Brazilian nor the Caucasian samples (adjusted p > 0.05). When comparing all Caucasian athletes regardless of their sporting discipline to C, we found that the A allele was overrepresented in athletes compared to C (adjusted p = 0.024). This association was even more pronounced when only elite-level athletes were considered (adjusted p = 0.00017). In conclusion, in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. This reinforces the

  15. Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and United States: cohort study

    PubMed Central

    Hwang, Thomas J; Sokolov, Elisaveta; Franklin, Jessica M; Kesselheim, Aaron S

    2016-01-01

    Objective To evaluate safety alerts and recalls, publication of key trial outcomes, and subsequent US approval of high profile medical devices introduced in the European Union. Design Cohort study. Setting Novel cardiovascular, orthopedic, and neurologic devices approved in the EU through Conformité Européenne marking between 2005 and 2010. Data sources Public and commercial databases searched up to January 2016 for press releases and announcements of approvals; public Food and Drug Administration and European regulatory authority databases for US approvals and safety alerts and recalls; and Medline, Embase, and Web of Science for peer reviewed publications. Main outcome measures We categorized the novelty of the devices in the study sample as a “major innovation” or an “other change,” and extracted descriptive data about the devices and information on any safety alerts and withdrawals. Linear regression models examined factors associated with differential EU and US approvals. Cox proportional hazards regression models were used to evaluate factors associated with safety alerts and recalls and the publication of trial outcomes for devices categorized as major innovations. Models controlled for time, therapeutic category, regulatory pathway, size of sponsoring company, and indicator variables for devices approved first in the EU and devices approved only in the EU. Results 67% (206/309) of devices identified were approved in both the US and the EU, of which 63% (129/206) were approved first in the EU. The unadjusted rate of safety alerts and recalls for devices approved first in the EU was 27% (62/232) compared with 14% (11/77) for devices approved first in the US. The adjusted hazard ratio for safety alerts and recalls was 2.9 (95% confidence interval 1.4 to 6.2) for devices approved first in the EU. The results of pivotal trials were published for 49% (37/75) of devices categorized as major innovations, with an overall publication rate of 37% five

  16. Vitamin D Deficiency in a Multiethnic Healthy Control Cohort and Altered Immune Response in Vitamin D Deficient European-American Healthy Controls

    PubMed Central

    Shah, Hemangi B.; Robertson, Julie M.; Fife, Dustin A.; Maecker, Holden T.; Du, Hongwu; Fathman, Charles G.; Chakravarty, Eliza F.; Scofield, R. Hal; Kamen, Diane L.; Guthridge, Joel M.; James, Judith A.

    2014-01-01

    Objective In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals. Methods Healthy individuals (n = 774) comprised of European-Americans (EA, n = 470), African–Americans (AA, n = 125), and Native Americans (NA, n = 179) were screened for 25-hydroxyvitamin D [25(OH)D] levels by ELISA. To identify the most noticeable effects of vitamin D on the immune system, 20 EA individuals with severely deficient (<11.3 ng/mL) and sufficient (>24.8 ng/mL) vitamin D levels were matched and selected for further analysis. Serum cytokine level measurement, immune cell phenotyping, and phosphoflow cytometry were performed. Results Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate analysis, AA, NA, and females with a high body mass index (BMI, >30) demonstrate higher rates of vitamin D deficiency (p<0.05). Individuals with vitamin D deficiency had significantly higher levels of serum GM-CSF (p = 0.04), decreased circulating activated CD4+ (p = 0.04) and CD8+ T (p = 0.04) cell frequencies than individuals with sufficient vitamin D levels. Conclusion A large portion of healthy individuals have vitamin D deficiency. These individuals have altered T and B cell responses, indicating that the absence of sufficient vitamin D levels could result in undesirable cellular and molecular alterations ultimately contributing to immune dysregulation. PMID:24727903

  17. Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years

    PubMed Central

    Dratva, Julia; Zemp, Elisabeth; Dharmage, Shyamali C.; Accordini, Simone; Burdet, Luc; Gislason, Thorarinn; Heinrich, Joachim; Janson, Christer; Jarvis, Deborah; de Marco, Roberto; Norbäck, Dan; Pons, Marco; Real, Francisco Gómez; Sunyer, Jordi; Villani, Simona; Probst-Hensch, Nicole; Svanes, Cecilie

    2016-01-01

    Objectives Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. Methods Spirometry data from two time points (follow-up time 9–11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28–73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. Results Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. Conclusion Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further. PMID:26811913

  18. Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.

    PubMed

    McKenzie, Fiona; Ferrari, Pietro; Freisling, Heinz; Chajès, Veronique; Rinaldi, Sabina; de Batlle, Jordi; Dahm, Christina C; Overvad, Kim; Baglietto, Laura; Dartois, Laureen; Dossus, Laure; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Rosso, Stefano; Bueno-de-Mesquita, H B As; May, Anne; Peeters, Petra H; Weiderpass, Elisabete; Buckland, Genevieve; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Andersson, Anne; Sund, Malin; Ericson, Ulrika; Wirfält, Elisabet; Key, Tim J; Travis, Ruth C; Gunter, Marc; Riboli, Elio; Vergnaud, Anne-Claire; Romieu, Isabelle

    2015-06-01

    Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. PMID:25379993

  19. Web-based multi-center data management system for clinical neuroscience research.

    PubMed

    Pozamantir, Alexander; Lee, Hedok; Chapman, Joab; Prohovnik, Isak

    2010-02-01

    Modern clinical research often involves multicenter studies, large and heterogeneous data flux, and intensive demands of collaboration, security and quality assurance. In the absence of commercial or academic management systems, we designed an open-source system to meet these requirements. Based on the Apache-PHP-MySQL platform on a Linux server, the system allows multiple users to access the database from any location on the internet using a web browser, and requires no specialized computer skills. Multi-level security system is implemented to safeguard the protected health information and allow partial or full access to the data by individual or class privilege. The system stores and manipulates various types of data including images, scanned documents, laboratory data and clinical ratings. Built-in functionality allows for various search, quality control, analytic data operations, visit scheduling and visit reminders. This approach offers a solution to a growing need for management of large multi-center clinical studies. PMID:20192052

  20. Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults.

    PubMed

    Liang, Peipeng; Shi, Lin; Chen, Nan; Luo, Yishan; Wang, Xing; Liu, Kai; Mok, Vincent C T; Chu, Winnie C W; Wang, Defeng; Li, Kuncheng

    2015-01-01

    Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18-76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population-specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID:26678304

  1. Insight into photofragment vector correlation by a multi-center impulsive model.

    PubMed

    Tsai, Po-Yu; Lin, King-Chuen

    2015-07-15

    A multi-center impulsive model has been recently developed to characterize the dynamic feature of product energy distribution in photodissociation of formaldehyde, H2CO → CO + H2. (J. Phys. Chem. A, 2015, 119, 29) The model is extended to predict the vector correlations among transition dipole moment μ of the parent molecule, recoil velocity v and rotational angular momentum j of the fragments produced via the transition state (TS) and roaming path. The correlation results of μ-j, j-j and μ-v vectors of the fragments are consistent with those reported using quasi-classical trajectory simulation on the global potential energy surface. In contrast to the TS route, the vector properties via the roaming path are loosely correlated. This work offers an alternative method to study stereodynamics of the photodissociation process, and is conducive to clarifying the origin of photofragment vector correlation especially for the roaming pathway. PMID:26150201

  2. Authorship in a Multi-Center Clinical Trial: the HF-ACTION Experience

    PubMed Central

    Whellan, DJ; Kraus, WE; Kitzman, DW; Rooney, B; Keteyian, SJ; Piña, IL; Ellis, SJ; Ghali, JK; Lee, K; Cooper, L; O'Connor, CM

    2015-01-01

    Background Few guidelines exist regarding authorship on manuscripts resulting from large multicenter trials. The HF-ACTION investigators devised a system to address assignment of authorship on trial publications and tested the outcomes in the course of conducting the large, multi-center, NHLBI-funded trial (n=2,331; 82 clinical sites; 3 countries). The HF-ACTION Authorship and Publication (HAP) Scoring System was designed to enhance rate of dissemination, recognize investigator contributions to the successful conduct of the trial, and harness individual expertise in manuscript generation. Methods The HAP score was generated by assigning points based on investigators’ participation in trial enrollment, follow-up, and adherence, as well as participation in committees and other trial activity. Overall publication rates, publication rates by author, publication rates by site, and correlation between site publication and HAP score using a Poisson regression model were examined. Results Fifty peer-reviewed, original manuscripts were published within 6.5 years following conclusion of study enrollment. In total, 137 different authors were named in at least 1 publication. Forty-five of the 82 sites (55%) had an author named to at least one manuscript. A Poisson regression model examining incident rate ratios revealed that a higher HAP score resulted in a higher incidence of a manuscript, with a 100-point increase in site score corresponding to an approximately 32% increase in the incidence of a published manuscript. Conclusions Given the success in publishing a large number of papers and widely distributing authorship, regular use of a transparent, objective authorship assignment system for publishing results from multi-center trials may be recommended to optimize fairness and dissemination of trial results. PMID:25819851

  3. A Prospective Multi-Center Audit of Nutrition Support Parameters Following Burn Injury.

    PubMed

    Kurmis, Rochelle; Heath, Kathryn; Ooi, Selena; Munn, Zachary; Forbes, Sharon; Young, Vicki; Rigby, Paul; Wood, Kate; Phillips, Frances; Greenwood, John

    2015-01-01

    The importance of nutrition support delivery to the severe burn-injured patient is well recognized, however, nutrition provision to the patient may be sub optimal in practice. The aim of this study was to conduct a prospective multi-center audit across Australia and New Zealand using the Joanna Briggs Institute Burns Node Nutrition audit criteria. Thirty-four patients with severe burn injury (≥20% TBSA in adults and ≥10% TBSA in children) were identified on admission or on referral to the Dietitian at the eight participating Burn Units between February 1, 2012 and April 30, 2012 for inclusion in the study. De-identified patient data was analyzed using the Joanna Briggs Institute, Practical Application of Clinical Evidence System. Compliance with individual audit criterion ranged from 33 to 100%. Provision of prescribed enteral feed volumes and weekly weighing of patients were highlighted as key areas for clinical improvement. Clinical audit is a valuable tool for evaluating current practice against best evidence to ensure that quality patient care is delivered. The use of the Joanna Briggs Institute Burns Node audit criteria has allowed for a standardized multi-center audit to be conducted. Improving nutrition support delivery in burn patients was identified as a key area requiring ongoing clinical improvement across Australia and New Zealand. Clinician feedback on use of the audit criteria will allow for future refinement of individual criterion, and presentation of results of this audit has resulted in a review of the Bi-National Burns Registry nutrition quality indicators. PMID:25094004

  4. Validation of Anthropometric Indices of Adiposity against Whole-Body Magnetic Resonance Imaging – A Study within the German European Prospective Investigation into Cancer and Nutrition (EPIC) Cohorts

    PubMed Central

    Neamat-Allah, Jasmine; Wald, Diana; Hüsing, Anika; Teucher, Birgit; Wendt, Andrea; Delorme, Stefan; Dinkel, Julien; Vigl, Matthaeus; Bergmann, Manuela M.; Feller, Silke; Hierholzer, Johannes; Boeing, Heiner; Kaaks, Rudolf

    2014-01-01

    Background In epidemiological studies, measures of body fat generally are obtained through anthropometric indices such as the body mass index (BMI), waist (WC), and hip circumferences (HC). Such indices, however, can only provide estimates of a person’s true body fat content, overall or by adipose compartment, and may have limited accuracy, especially for the visceral adipose compartment (VAT). Objective To determine the extent to which different body adipose tissue compartments are adequately predicted by anthropometry, and to identify anthropometric measures alone, or in combination to predict overall adiposity and specific adipose tissue compartments, independently of age and body size (height). Methods In a sub-study of 1,192 participants of the German EPIC (European Prospective Investigation into Cancer and Nutrition) cohorts, whole-body MRI was performed to determine adipose and muscle tissue compartments. Additional anthropometric measurements of BMI, WC and HC were taken. Results After adjusting for age and height, BMI, WC and HC were better predictors of total body volume (TBV), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) than for VAT, coronary adipose tissue (CAT) and skeletal muscle tissue (SMT). In both sexes, BMI was the best predictor for TBV (men: r = 0.72 [0.68–0.76], women: r = 0.80 [0.77–0.83]) and SMT (men: r = 0.52 [0.45–0.57], women: r = 0.48 [0.41–0.54]). WC was the best predictor variable for TAT (r = 0.48 [0.41–0.54]), VAT (r = 0.44 [0.37–0.50]) and CAT (r = 0.34 [0.26–0.41]) (men), and for VAT (r = 0.42 [0.35–0.49]) and CAT (r = 0.29 [0.22–0.37]) (women). BMI was the best predictor for TAT (r = 0.49 [0.43–0.55]) (women). HC was the best predictor for SAT (men (r = 0.39 [0.32–0.45]) and women (r = 0.52 [0.46–0.58])). Conclusions Especially the volumes of internal body fat compartments are poorly predicted by anthropometry. A possible implication

  5. 77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ...-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal Register notice published on February 24, 2012 (77 FR 11136) announcing the submission to OMB of the project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (AsiaLymph) (NCI)'' was submitted with...

  6. Factors Influencing Medical Student Attrition and Their Implications in a Large Multi-Center Randomized Education Trial

    ERIC Educational Resources Information Center

    Kalet, A.; Ellaway, R. H.; Song, H. S.; Nick, M.; Sarpel, U.; Hopkins, M. A.; Hill, J.; Plass, J. L.; Pusic, M. V.

    2013-01-01

    Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the…

  7. Multi-Center Analysis of Novel and Established Variables Associated with Successful Human Islet Isolation Outcomes

    PubMed Central

    Kaddis, J.S; Danobeitia, J.S.; Niland, J.C.; Stiller, T.; Fernandez, L.A.

    2010-01-01

    Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as post-purification islet equivalent count, dichotomized into yields ≥ 315,000 or ≤ 220,000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution, and a fatty pancreas improves outcome. In conclusion, this multi-center analysis highlights the importance of carefully reviewing of all donor, pancreas, and processing parameters prior to isolation and transplantation. PMID:20055802

  8. Calculations of fast ion collisions with multi-center molecular targets

    NASA Astrophysics Data System (ADS)

    Kirchner, Tom

    2011-05-01

    The theoretical treatment of ion-molecule collisions is challenging for several reasons: the systems have many degrees of freedom, a rather complex geometry, and the electron dynamics might be nonperturbative and involve electron-electron interaction effects. However, the interest in accurate calculations has been growing recently. An important reason for this development is the relevance of ion-molecule collisions for a number of fields, such as atmospheric science, and the understanding of radiation damage of biological tissue. We have developed a new approach to meet these challenges. It disregards rovibrational motion, but it does address the multi-center geometry of the system and the generally nonperturbative nature of the electron dynamics. The key ingredients are an expansion of the initially populated molecular orbitals in terms of a single-center basis and a spectral representation of the molecular Hamiltonian. This facilitates a separation of molecular geometry and collision dynamics and makes it possible to use well-established ion-atom methods with relatively minor modifications. We have extended our basis generator method to deal with the collision dynamics and report on results for ionization and fragmentation of water molecules by proton and He+ ion impact over wide ranges of collision energies. For the case of He+ impact this will include a discussion of effects due to the presence of the projectile electron. This work has been supported by the Natural Sciences and Engineering Research Council of Canada.

  9. Photorejuvenation with intense pulsed light: results of a multi-center study.

    PubMed

    Sadick, Neil S; Weiss, Robert; Kilmer, Suzanne; Bitter, Patrick

    2004-01-01

    This multi-center study evaluating the role of Intense Pulsed Light (IPL) in the non-ablative rejuvenation of Type I and Type II photoaged skin study was conducted in order to evaluate the clinical efficacy and safety of using IPL in treating clinical indications associated with photoaged skin. Ninety-three patients of Fitzpatrick skin phenotypes I-III, Fitzpatrick Wrinkle Classes I-II, and Elastosis Scores 1-6 were enrolled in the study. Up to five treatments were performed at 4-week intervals with follow-up visits at 4 and 6 months after the last treatment. Patients received full-face treatments using the recommended parameters of the Quantum SR/HR (Lumenis Ltd.) with the 560 or 640 nm cutoff filter. Parameters of elastometry, physicians' evaluation of the Elastosis Score ('W/ES'), and global improvement as well as patient satisfaction were analyzed. Results showed that the average Fitzpatrick W/ES improved significantly (p<0.001) by 1.39 and 1.32 units at the 4 and 6 months follow-ups, respectively; an improved W/ES evaluation was recorded for 82% and 75% of the patients at each of these time points. In conclusion, IPL treatment is an effective non-invasive, non-ablative method for rejuvenating photoaged skin with minimal adverse events, no downtime, excellent long-term results, and a very high measure of patient satisfaction. PMID:14964745

  10. Vitamin D Deficiency in Healthy Male Population: Results of the Iranian Multi- Center Osteoporosis Study

    PubMed Central

    Rahnavard, Z; Eybpoosh, S; Homami, M Rezaei; Meybodi, HR Aghaei; Azemati, B; Heshmat, R; Larijani, B

    2010-01-01

    Background: The prevalence of vitamin D deficiency and its causative factors has been estimated more frequently in elder population, women, and patients with osteoporosis in different countries, but this issue is less defined in male population within different age groups especially in Asian countries. Therefore, we studied the role of effective factors in vitamin D deficiency and its prevalence in Iranian healthy men. Methods: This study was a multi center and carried out in five metropolitans in Iran. Serum 25 Hydroxy vitamin D and other biochemical variables were determined in 2396 healthy men in late winter of 2001. Results: 68.8% of participants suffered from vitamin D deficiency. Vitamin D levels were the highest in Bushehr (n= 111, 40.3%) (P< 0.05) and between Shiraz and Tabriz, Shiraz had the better values (P< 0.05). Tehran had the highest prevalence of vitamin D deficiency (n= 380, n= 85.7%). Geographical zone independently predicted vitamin D status (P< 0.05). There was not any association among age (r= 0.035, P> 0.05), physical activity (r= 0.023, P> 0.05), and exposure of face & hands to sunlight (r= 0.022, P> 0.05) with vitamin D levels. Conclusion: Prevalence of vitamin D deficiency in Iranian male population is high, considering Iranian cultural and geographical zones, food fortification and life style modification is recommended. PMID:23113022

  11. Multi-center, multi-topic heart sound databases and their applications.

    PubMed

    Xie, Meilan; Xiao, Shouzhong; Liu, Tianhu; Yi, Qijian; You, Fengzhi; Guo, Xingming; Shao, Yong; Huo, Junmimg; Du, Deqi; Xu, Dongmei; Wu, Wenzhu; Xiao, Zifu; Yang, Yong; Guo, Weizhen

    2012-02-01

    This paper describes a large resource of multi-center and multi-topic heart sound databases, which were based on the measured data from more than 9,000 heart sound samples (saved in WAV file format). According to different research topics, these samples were respectively stored in different folders (corresponding to different research topics and distributed over various cooperative research centers), most of which as subfolds were stored in a pooled folder in the principal center. According to different research topics, the measured data from these samples were used to create different databases. Relevant data for a specific topic can be pooled in a large database for further analysis. This resource is shared by members of related centers for their own specific topic. The applications of this resource include evaluation of cardiac safety of pregnant women, evaluation of cardiac reserve for children, athletes, addicts, astronauts, and general populations, as well as studies on a bedside method for evaluating cardiac energy, reversal of S1-S2 ratio, etc. PMID:20703751

  12. Distributed Scheduling Architecture for Multi-Center Time-Based Metering

    NASA Technical Reports Server (NTRS)

    Landry, Steven; Farley, Todd; Foster, John; Green, Steve; Hoang, Ty; Wong, Gregory L.

    2003-01-01

    The Traffic Management Advisor (TMA) is an air traffic control automation system currently in use in seven Air Route Traffic Control Centers (ARTCCs) to enable time based metering to busy airports within their airspace. However, this system is limited to operation within a single ARTCC, within about a 200 nautical mile radius of the airport, and on relatively simple streams of traffic. The need for coordinated metering within a greater (300+ nautical mile) radius of an airport, on streams of traffic with significant branching, and across ARTCC boundaries, has been identified. Early tests revealed that TMA could not simply be scaled up to handle such a problem. Instead, a loosely coupled hierarchy of schedules, in which constraints from downstream schedules are passed upstream, is required. Such an architecture reduces the reliance on distant projections of arrival times, making schedules robust to changes in sequence and to additions of aircraft (such as aircraft departing inside the system s scheduling horizon). This architecture is also scaleable, easily reconfigurable, and can be networked together. As such, it can be adapted for use in any size or configuration of airspace and with any number of airports delivering restrictions. An implementation of this distributed scheduling architecture is currently undergoing testing in the TMA-Multi Center system. This paper describes the architecture and its motivation.

  13. ImTK: an open source multi-center information management toolkit

    NASA Astrophysics Data System (ADS)

    Alaoui, Adil; Ingeholm, Mary Lou; Padh, Shilpa; Dorobantu, Mihai; Desai, Mihir; Cleary, Kevin; Mun, Seong K.

    2008-03-01

    The Information Management Toolkit (ImTK) Consortium is an open source initiative to develop robust, freely available tools related to the information management needs of basic, clinical, and translational research. An open source framework and agile programming methodology can enable distributed software development while an open architecture will encourage interoperability across different environments. The ISIS Center has conceptualized a prototype data sharing network that simulates a multi-center environment based on a federated data access model. This model includes the development of software tools to enable efficient exchange, sharing, management, and analysis of multimedia medical information such as clinical information, images, and bioinformatics data from multiple data sources. The envisioned ImTK data environment will include an open architecture and data model implementation that complies with existing standards such as Digital Imaging and Communications (DICOM), Health Level 7 (HL7), and the technical framework and workflow defined by the Integrating the Healthcare Enterprise (IHE) Information Technology Infrastructure initiative, mainly the Cross Enterprise Document Sharing (XDS) specifications.

  14. A multi-center milestone study of clinical vertebral CT segmentation.

    PubMed

    Yao, Jianhua; Burns, Joseph E; Forsberg, Daniel; Seitel, Alexander; Rasoulian, Abtin; Abolmaesumi, Purang; Hammernik, Kerstin; Urschler, Martin; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Castro-Mateos, Isaac; Pozo, Jose M; Frangi, Alejandro F; Summers, Ronald M; Li, Shuo

    2016-04-01

    A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention. PMID:26878138

  15. DICOM for Clinical Research: PACS-Integrated Electronic Data Capture in Multi-Center Trials.

    PubMed

    Haak, Daniel; Page, Charles-E; Reinartz, Sebastian; Krüger, Thilo; Deserno, Thomas M

    2015-10-01

    Providing surrogate endpoints in clinical trials, medical imaging has become increasingly important in human-centered research. Nowadays, electronic data capture systems (EDCS) are used but binary image data is integrated insufficiently. There exists no structured way, neither to manage digital imaging and communications in medicine (DICOM) data in EDCS nor to interconnect EDCS with picture archiving and communication systems (PACS). Manual detours in the trial workflow yield errors, delays, and costs. In this paper, requirements for a DICOM-based system interconnection of EDCS and research PACS are analysed. Several workflow architectures are compared. Optimized for multi-center trials, we propose an entirely web-based solution integrating EDCS, PACS, and DICOM viewer, which has been implemented using the open source projects OpenClinica, DCM4CHEE, and Weasis, respectively. The EDCS forms the primary access point. EDCS to PACS interchange is integrated seamlessly on the data and the context levels. DICOM data is viewed directly from the electronic case report form (eCRF), while PACS-based management is hidden from the user. Data privacy is ensured by automatic de-identification and re-labelling with study identifiers. Our concept is evaluated on a variety of 13 DICOM modalities and transfer syntaxes. We have implemented the system in an ongoing investigator-initiated trial (IIT), where five centers have recruited 24 patients so far, performing decentralized computed tomography (CT) screening. Using our system, the chief radiologist is reading DICOM data directly from the eCRF. Errors and workflow processing time are reduced. Furthermore, an imaging database is built that may support future research. PMID:26001521

  16. The Multi-Center Airborne Coherent Atmospheric Wind Sensor: Recent Measurements and Future Applications

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Howell, James N.; Darby, Lisa S.; Tratt, David M.; Menzies, Robert T.

    1999-01-01

    The coherent Doppler lidar, when operated from an airborne platform, offers a unique measurement capability for study of atmospheric dynamical and physical properties. This is especially true for scientific objectives requiring measurements in optically-clear air, where other remote sensing technologies such as Doppler radar are at a disadvantage in terms of spatial resolution and coverage. Recent experience suggests airborne coherent Doppler lidar can yield unique wind measurements of--and during operation within--extreme weather phenomena. This paper presents the first airborne coherent Doppler lidar measurements of hurricane wind fields. The lidar atmospheric remote sensing groups of National Aeronautics and Space Administration (NASA) Marshall Space Flight Center, National Oceanic and Atmospheric Administration (NOAA) Environmental Technology Laboratory, and Jet Propulsion Laboratory jointly developed an airborne lidar system, the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS). The centerpiece of MACAWS is the lidar transmitter from the highly successful NOAA Windvan. Other field-tested lidar components have also been used, when feasible, to reduce costs and development time. The methodology for remotely sensing atmospheric wind fields with scanning coherent Doppler lidar was demonstrated in 1981; enhancements were made and the system was reflown in 1984. MACAWS has potentially greater scientific utility, compared to the original airborne scanning lidar system, owing to a factor of approx. 60 greater energy-per-pulse from the NOAA transmitter. MACAWS development was completed and the system was first flown in 1995. Following enhancements to improve performance, the system was re-flown in 1996 and 1998. The scientific motivation for MACAWS is three-fold: obtain fundamental measurements of subgrid scale (i.e., approx. 2-200 km) processes and features which may be used to improve parameterizations in hydrological, climate, and general

  17. Multi-Center Implementation of NPR 7123.1A: A Collaborative Effort

    NASA Technical Reports Server (NTRS)

    Hall, Phillip B.; McNelis, Nancy B.

    2011-01-01

    Collaboration efforts between MSFC and GRC Engineering Directorates to implement the NASA Systems Engineering (SE) Engine have expanded over the past year to include other NASA Centers. Sharing information on designing, developing, and deploying SE processes has sparked further interest based on the realization that there is relative consistency in implementing SE processes at the institutional level. This presentation will provide a status on the ongoing multi-center collaboration and provide insight into how these NPR 7123.1A SE-aligned directives are being implemented and managed to better support the needs of NASA programs and projects. NPR 7123.1A, NASA Systems Engineering Processes and Requirements, was released on March 26, 2007 to clearly articulate and establish the requirements on the implementing organization for performing, supporting, and evaluating SE activities. In early 2009, MSFC and GRC Engineering Directorates undertook a collaborative opportunity to share their research and work associated with developing, updating and revising their SE process policy to comply and align with NPR 7123.1A. The goal is to develop instructions, checklists, templates, and procedures for each of the 17 SE process requirements so that systems engineers will be a position to define work that is process-driven. Greater efficiency and more effective technical management will be achieved due to consistency and repeatability of SE process implementation across and throughout each of the NASA centers. An added benefit will be to encourage NASA centers to pursue and collaborate on joint projects as a result of using common or similar processes, methods, tools, and techniques.

  18. Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

    PubMed

    van de Bank, B L; Emir, U E; Boer, V O; van Asten, J J A; Maas, M C; Wijnen, J P; Kan, H E; Oz, G; Klomp, D W J; Scheenen, T W J

    2015-03-01

    The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field. PMID:25581510

  19. Distribution of guidance models for cardiac resynchronization therapy in the setting of multi-center clinical trials

    NASA Astrophysics Data System (ADS)

    Rajchl, Martin; Abhari, Kamyar; Stirrat, John; Ukwatta, Eranga; Cantor, Diego; Li, Feng P.; Peters, Terry M.; White, James A.

    2014-03-01

    Multi-center trials provide the unique ability to investigate novel techniques across a range of geographical sites with sufficient statistical power, the inclusion of multiple operators determining feasibility under a wider array of clinical environments and work-flows. For this purpose, we introduce a new means of distributing pre-procedural cardiac models for image-guided interventions across a large scale multi-center trial. In this method, a single core facility is responsible for image processing, employing a novel web-based interface for model visualization and distribution. The requirements for such an interface, being WebGL-based, are minimal and well within the realms of accessibility for participating centers. We then demonstrate the accuracy of our approach using a single-center pacemaker lead implantation trial with generic planning models.

  20. MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

    PubMed Central

    Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

    2011-01-01

    Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

  1. MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

    PubMed

    Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

    2011-01-01

    Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

  2. Nested Cohort

    Cancer.gov

    NestedCohort is an R software package for fitting Kaplan-Meier and Cox Models to estimate standardized survival and attributable risks for studies where covariates of interest are observed on only a sample of the cohort.

  3. Clinical and functional outcomes of the PCCP study: a multi-center prospective study in Italy.

    PubMed

    Antonini, G; Giancola, R; Berruti, D; Blanchietti, E; Pecchia, P; Francione, V; Greco, P; Russo, T C; Pietrogrande, L

    2013-04-01

    The standard surgical management of hip fractures is associated with tissue trauma and bleeding which are added to the fracture injury. The percutaneous compression plate (PCCP) is a minimally invasive device that has been demonstrated in previous studies to reduce postoperative complications and blood loss. This prospective, multi-center, observational study assessed clinical and functional outcomes with PCCP as treatment for trochanteric fractures. Patients with a stable or unstable proximal femoral fracture of type AO 31.A1 or 31.A2 were enrolled in eight hospitals in Italy. The primary outcome of interest was the recovery of the pre-fracture functional status at 1-year follow-up; secondary outcomes of interest included blood transfusions, surgical time, complications, and mortality. A total of 273 patients were enrolled. The ASA score was 3 or 4 in 72.5 % of patients. The mean surgical time was 44.1 min; the mean post-surgery blood transfusions was 0.9 units. At 1 year, 48 patients (17.6 %) died, 28 (10.2 %) were lost to follow-up, 4 patients (1.5 %) were excluded, hence 193 patients (70.3 %) were available for final evaluation. At the 1-year follow-up visit, 51.9 % of patients recovered or improved their pre-fracture modified Harris Hip Score, 49.1 % of patients improved or maintained their walking abilities, and 66.6 % of patients residing at home pre-surgery maintained their domicile. The overall mortality rate was 17.6 %. Major complications included two fracture collapses, one excessive sliding of the cephalic screw leading to a partial fracture collapse and one back-out of the diaphyseal screw. This study demonstrates that treatment of trochanteric fractures with PCCP gives good outcomes and significant advantages such as low blood loss, short surgical time, low risk of complications, and good functional recovery in the majority of the patients. PMID:23543403

  4. The Effects of the Uncertainty of Departures on Multi-Center Traffic Management Advisor (TMA) Scheduling

    NASA Technical Reports Server (NTRS)

    Thipphavong, Jane; Landry, Steven J.

    2005-01-01

    The Multi-center Traffic Management Advisor (McTMA) provides a platform for regional or national traffic flow management, by allowing long-range cooperative time-based metering to constrained resources, such as airports or air traffic control center boundaries. Part of the demand for resources is made up of proposed departures, whose actual departure time is difficult to predict. For this reason, McTMA does not schedule the departures in advance, but rather relies on traffic managers to input their requested departure time. Because this happens only a short while before the aircraft's actual departure, McTMA is unable to accurately predict the amount of delay airborne aircraft will need to take in order to accommodate the departures. The proportion of demand which is made up by such proposed departures increases as the horizon over which metering occurs gets larger. This study provides an initial analysis of the severity of this problem in a 400-500 nautical mile metering horizon and discusses potential solutions to accommodate these departures. The challenge is to smoothly incorporate departures with the airborne stream while not excessively delaying the departures.' In particular, three solutions are reviewed: (1) scheduling the departures at their proposed departure time; (2) not scheduling the departures in advance; and (3) scheduling the departures at some time in the future based on an estimated error in their proposed time. The first solution is to have McTMA to automatically schedule the departures at their proposed departure times. Since the proposed departure times are indicated in their flight times in advance, this method is the simplest, but studies have shown that these proposed times are often incorrect2 The second option is the current practice, which avoids these inaccuracies by only scheduling aircraft when a confirmed prediction of departure time is obtained from the tower of the departure airport. Lastly, McTMA can schedule the departures at a

  5. Time to Positivity and Detection of Growth in Anaerobic Blood Culture Vials Predict the Presence of Candida glabrata in Candidemia: a Two-Center European Cohort Study

    PubMed Central

    Kaasch, Achim J.; Soriano, Alex; Torres, Jorge-Luis; Vergara, Andrea; Morata, Laura; Zboromyrska, Yuliya; De La Calle, Cristina; Alejo, Izaskun; Hernández, Cristina; Cardozo, Celia; Marco, Franscesc; Del Río, Ana; Almela, Manel; Mensa, Josep; Martínez, José Antonio

    2014-01-01

    This study shows the accuracy of exclusive or earlier growth in anaerobic vials to predict Candida glabrata in a large series of candidemic patients from two European hospitals using the Bactec 9240 system. Alternatively, C. glabrata can be predicted by a time to positivity cutoff value, which should be determined for each setting. PMID:24899027

  6. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study

    PubMed Central

    2014-01-01

    Introduction Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. Methods In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. Results Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). Conclusions A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality. PMID:24589043

  7. Data management in multi-center clinical trials and the role of a nation-wide computer network. A 5 year evaluation.

    PubMed Central

    Gerritsen, M. G.; Sartorius, O. E.; vd Veen, F. M.; Meester, G. T.

    1993-01-01

    Multidisciplinary collaboration in multi-center trials needs a formalized data management structure to ensure true progress monitoring and high quality research data. Cadans, a customized facility for data management, related to the Interuniversity Cardiology Institute of the Netherlands, designed a computer-based data management system for multidisciplinary multi-center collaborative research projects. In this paper we describe the system and the role of integrated access to research databases on a data network. Areas of concern are also discussed. PMID:8130557

  8. Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    PubMed

    Kyrø, Cecilie; Olsen, Anja; Bueno-de-Mesquita, H B As; Skeie, Guri; Loft, Steffen; Åman, Per; Leenders, Max; Dik, Vincent K; Siersema, Peter D; Pischon, Tobias; Christensen, Jane; Overvad, Kim; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Cottet, Vanessa; Kühn, Tilman; Chang-Claude, Jenny; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Oikonomidou, Despoina; Masala, Giovanna; Pala, Valeria; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Peeters, Petra H; Bakken, Toril; Weiderpass, Elisabete; Asli, Lene Angell; Sánchez, Soledad; Jakszyn, Paula; Sánchez, María-José; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Ljuslinder, Ingrid; Palmqvist, Richard; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Travis, Ruth C; Slimani, Nadia; Freisling, Heinz; Ferrari, Pietro; Gunter, Marc J; Murphy, Neil; Riboli, Elio; Tjønneland, Anne; Landberg, Rikard

    2014-05-28

    Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye. PMID:24521535

  9. Contraceptive Use and the Risk of Ectopic Pregnancy: A Multi-Center Case-Control Study

    PubMed Central

    Meng, Chun-Xia; Ping, Hua; Qin, Guo-Juan; Cao, Shu-Jun; Xi, Xiaowei; Zhu, Qian; Li, Xiao-Cui; Zhang, Jian

    2014-01-01

    Objective To evaluate the association between the risk of ectopic pregnancy (EP) and the use of common contraceptives during the previous and current conception/menstrual cycle. Methods A multi-center case-control study was conducted in Shanghai. Women diagnosed with EP were recruited as the case group (n = 2,411). Women with intrauterine pregnancy (IUP) (n = 2,416) and non-pregnant women (n = 2,419) were matched as controls at a ratio of 1∶1. Information regarding the previous and current use of contraceptives was collected. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and the corresponding 95% confidential intervals (CIs). Results Previous use of intrauterine devices (IUDs) was associated with a slight risk of ectopic pregnancy (AOR1 = 1.87 [95% CI: 1.48–2.37]; AOR2 = 1.84 [1.49–2.27]), and the risk increased with the duration of previous use (P1 for trend <10−4, P2 for trend <10−4). The current use of most contraceptives reduced the risk of both unwanted IUP (condom: AOR = 0.04 [0.03–0.05]; withdrawal method: AOR = 0.10 [0.07–0.13]; calendar rhythm method: AOR = 0.54 [0.40–0.73]; oral contraceptive pills [OCPs]: AOR = 0.03 [0.02–0.08]; levonorgestrel emergency contraception [LNG-EC]: AOR = 0.22 [0.16–0.30]; IUDs: AOR = 0.01 [0.005–0.012]; tubal sterilization: AOR = 0.01 [0.001–0.022]) and unwanted EP (condom: AOR1 = 0.05 [0.04–0.06]; withdrawal method: AOR1 = 0.13 [0.09–0.19]; calendar rhythm method: AOR1 = 0.66 [0.48–0.91]; OCPs: AOR1 = 0.14 [0.07–0.26]; IUDs: AOR1 = 0.17 [0.13–0.22]; tubal sterilization: AOR1 = 0.04 [0.02–0.08]). However, when contraception failed and pregnancy occurred, current use of OCPs (AOR2 = 4.06 [1.64–10.07]), LNG-EC (AOR2 = 4.87 [3.88–6.10]), IUDs (AOR2 = 21.08 [13.44–33.07]), and tubal sterilization (AOR2 = 7.68 [1.69–34.80]) increased the risk of EP compared

  10. Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin

    PubMed Central

    Eastwood, S. V.; Tillin, T.; Mayet, J.; Shibata, D. K.; Wright, A.; Heasman, J.; Beauchamp, N.; Forouhi, N. G.; Hughes, A. D.; Chaturvedi, N.

    2015-01-01

    Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South-Asian origin. Methods For 682 European and 520 South-Asian men and women, aged 58–85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist–hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P=0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the

  11. Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the European Prospective Investigation into Nutrition and Cancer (EPIC-Italy) cohort.

    PubMed

    Cordero, Francesca; Ferrero, Giulio; Polidoro, Silvia; Fiorito, Giovanni; Campanella, Gianluca; Sacerdote, Carlotta; Mattiello, Amalia; Masala, Giovanna; Agnoli, Claudia; Frasca, Graziella; Panico, Salvatore; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Naccarati, Alessio

    2015-10-01

    The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset. PMID:26168820

  12. Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models

    PubMed Central

    Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P.

    2016-01-01

    In a phase III multi-center cancer clinical trial or large public health studies, sample size is predetermined to achieve desired power and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date based on the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of NSABP trial B-38. The results showed that application of proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. PMID:22411544

  13. Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians

    PubMed Central

    Appleby, Paul N; Allen, Naomi E; Key, Timothy J

    2011-01-01

    Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort of mainly health conscious participants recruited from around the United Kingdom. Participants 47 033 men and women living in England or Scotland of whom 15 459 (33%) reported consuming a vegetarian diet. Main outcome measures Diet group was assessed at baseline; intake of dietary fibre was estimated from a 130 item validated food frequency questionnaire. Cases of diverticular disease were identified through linkage with hospital records and death certificates. Hazard ratios and 95% confidence intervals for the risk of diverticular disease by diet group and fifths of intake of dietary fibre were estimated with multivariate Cox proportional hazards regression models. Results After a mean follow-up time of 11.6 years, there were 812 cases of diverticular disease (806 admissions to hospital and six deaths). After adjustment for confounding variables, vegetarians had a 31% lower risk (relative risk 0.69, 95% confidence interval 0.55 to 0.86) of diverticular disease compared with meat eaters. The cumulative probability of admission to hospital or death from diverticular disease between the ages of 50 and 70 for meat eaters was 4.4% compared with 3.0% for vegetarians. There was also an inverse association with dietary fibre intake; participants in the highest fifth (≥25.5 g/day for women and ≥26.1 g/day for men) had a 41% lower risk (0.59, 0.46 to 0.78; P<0.001 trend) compared with those in the lowest fifth (<14 g/day for both women and men). After mutual adjustment, both a vegetarian diet and a higher intake of fibre were significantly associated with a lower risk of diverticular disease. Conclusions Consuming a vegetarian diet and a high intake of dietary fibre were both associated with a lower risk of admission to hospital or death from diverticular disease. PMID:21771850

  14. Consistency of vitamin and/or mineral supplement use and demographic, lifestyle and health-status predictors: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort.

    PubMed

    Li, Kuanrong; Kaaks, Rudolf; Linseisen, Jakob; Rohrmann, Sabine

    2010-10-01

    Cross-sectional studies suggest that dietary supplement use is associated with favourable demographic and lifestyle factors and certain health conditions. However, factors that affect the consistency of supplement use have not been investigated in prospective cohort studies. The aim of the present study was to seek baseline demographic, lifestyle and health-status predictors of subsequent consistent vitamin and/or mineral supplement use. A total of 8968 men and 10,672 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, who answered the supplement-use questions in the baseline survey and two follow-up surveys, were categorised into three groups: consistent, inconsistent and never users. At baseline, 28.5 % of men and 38.6 % of women reported vitamin and/or mineral supplement use. After a median follow-up of 8.5 years, 14.6 % of men and 22.9 % of women were consistent users. During follow-up, 36.0 % of male and 26.6 % of female initial users stopped supplement use, whereas 27.8 % of male and 39.4 % of female initial non-users started supplement use. Women were more likely to be consistent users than men. Older age (≥ 50 years), lower BMI (< 25 kg/m2) and self-reported hyperlipidaemia were common predictors of consistent use for both sexes. Additional predictors included higher educational level for men, and being more physically active and higher lifetime alcohol consumption for women. Consistent users had the highest intake of dairy products, fish, fruits and vegetables, and wine but the lowest intake of total meat. We concluded that supplement use is a fairly unstable behaviour in free-living individuals. Individuals with a favourable lifestyle and healthier diet are more likely to show consistent supplementation. PMID:20441685

  15. Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan.

    PubMed

    Ono, Nobuyuki; Niiro, Hiroaki; Ueda, Akira; Sawabe, Takuya; Nishizaka, Hiroaki; Furugo, Isao; Yoshizawa, Seiji; Yoshizawa, Shigeru; Tsukamoto, Hiroshi; Kiyohara, Chikako; Tada, Yoshifumi; Horiuchi, Takahiko

    2015-03-01

    We studied the clinico-pathological differences among PR3-ANCA-positive granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified using the European Medicines Agency classification. We retrospectively analyzed 38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %) of patients with MPO-GPA were woman, a significantly greater proportion than for PR3-GPA. We also found that ear, nose and throat (ENT), nervous system involvement were significantly more common in MPO-GPA, but renal function was less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more frequently than MPA, but overall survival was significantly better (P < 0.01 and P < 0.05, respectively). Univariate analysis identified the following factors as predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005) Cr ≥ 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older women and was associated with otitis media, nervous system involvement, mild renal impairment and more favorable outcome. It is clinically useful to differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV. PMID:25129031

  16. The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort

    PubMed Central

    Mencacci, Niccolo E.; R'bibo, Léa; Bandres-Ciga, Sara; Carecchio, Miryam; Zorzi, Giovanna; Nardocci, Nardo; Garavaglia, Barbara; Batla, Amit; Bhatia, Kailash P.; Pittman, Alan M.; Hardy, John; Weissbach, Anne; Klein, Christine; Gasser, Thomas; Lohmann, Ebba; Wood, Nicholas W.

    2015-01-01

    Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ∼30–50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregation Consortium). The variant was detected in a single sporadic case with M-D, but in none of the 146 probands with familial M-D. Overall, the variant was present at comparable frequencies in M-D cases (1 out of 520; 0.19%) and healthy controls (1 out of 489; 0.2%). A similar frequency of the variant was also reported in all publicly available databases. These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D. PMID:26157024

  17. LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants.

    PubMed

    Andreotti, Gabriella; Karami, Sara; Pfeiffer, Ruth M; Hurwitz, Lauren; Liao, Linda M; Weinstein, Stephanie J; Albanes, Demetrius; Virtamo, Jarmo; Silverman, Debra T; Rothman, Nathaniel; Moore, Lee E

    2014-03-01

    Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2-Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2-Q4 vs. Q1 OR = 1.48, 95% CI: 1.00-2.20) and statistically significant among male smokers (Q2-Q4 vs. Q1 OR = 1.83, 95% CI: 1.14-2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2-Q4 vs. Q1: OR = 2.31, 95% CI: 1.62-3.30) and a highly significant trend was observed (P = 8.7 × 10(-7)). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52-2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers. PMID:24316677

  18. Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

    PubMed Central

    Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

    2013-01-01

    New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

  19. Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

    PubMed Central

    Vogiatzoglou, Anna; Mulligan, Angela A.; Bhaniani, Amit; Lentjes, Marleen A.H.; McTaggart, Alison; Luben, Robert N.; Heiss, Christian; Kelm, Malte; Merx, Marc W.; Spencer, Jeremy P.E.; Schroeter, Hagen; Khaw, Kay-Tee; Kuhnle, Gunter G.C.

    2015-01-01

    Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034 mg/d (range: 0–8531 mg/d) for men and 970 mg/d (0–6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0–3248 mg/d) for men and 217 (0–2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk. PMID:25795512

  20. Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins

    PubMed Central

    Proebstle, T M; Alm, B J; Göckeritz, O; Wenzel, C; Noppeney, T; Lebard, C; Sessa, C; Creton, D; Pichot, O

    2015-01-01

    Background This was a prospective study of radiofrequency segmental thermal ablation (RFA) for the treatment of incompetent varicose great saphenous veins (GSVs). The present report describes long-term follow-up at 5 years. Methods The 5-year follow-up of this multicentre European study included assessment of the Venous Clinical Severity Score (VCSS), and GSV occlusion and reflux on duplex imaging. Results A total of 225 patients had 295 GSVs treated by RFA, achieving an initial vein occlusion rate of 100 per cent. With 80·0 per cent compliance, Kaplan–Meier analyses showed a GSV occlusion rate of 91·9 per cent and a reflux-free rate of 94·9 per cent at 5 years. Among the 15 GSVs noted with reflux during follow-up, only three showed full recanalization of the GSV at 1 week, 6 months and 3 years. Of the 12 legs with partial recanalization, reflux originated at the saphenofemoral junction in ten, with a mean length of the patent segment of 5·8 (range 3·2–10) cm; only six patients were symptomatic. Mean(s.d.) VCSS scores improved from 3·9(2·1) at baseline to 0·6(1·2), 0·9(1·3) and 1·3(1·7) at 1, 3 and 5 years. Conclusion At 5 years RFA proved to be an efficient endovenous treatment for incompetent GSVs in terms of sustained clinical and anatomical success for the vast majority of treated patients. PMID:25627262

  1. Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk).

    PubMed

    Vogiatzoglou, Anna; Mulligan, Angela A; Bhaniani, Amit; Lentjes, Marleen A H; McTaggart, Alison; Luben, Robert N; Heiss, Christian; Kelm, Malte; Merx, Marc W; Spencer, Jeremy P E; Schroeter, Hagen; Khaw, Kay-Tee; Kuhnle, Gunter G C

    2015-07-01

    Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034mg/d (range: 0-8531mg/d) for men and 970mg/d (0-6695mg/d) for women, median intake of flavan-3-ol monomers was 233mg/d (0-3248mg/d) for men and 217 (0-2712mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk. PMID:25795512

  2. ICA-based artifact removal diminishes scan site differences in multi-center resting-state fMRI

    PubMed Central

    Feis, Rogier A.; Smith, Stephen M.; Filippini, Nicola; Douaud, Gwenaëlle; Dopper, Elise G. P.; Heise, Verena; Trachtenberg, Aaron J.; van Swieten, John C.; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Mackay, Clare E.

    2015-01-01

    Resting-state fMRI (R-fMRI) has shown considerable promise in providing potential biomarkers for diagnosis, prognosis and drug response across a range of diseases. Incorporating R-fMRI into multi-center studies is becoming increasingly popular, imposing technical challenges on data acquisition and analysis, as fMRI data is particularly sensitive to structured noise resulting from hardware, software, and environmental differences. Here, we investigated whether a novel clean up tool for structured noise was capable of reducing center-related R-fMRI differences between healthy subjects. We analyzed three Tesla R-fMRI data from 72 subjects, half of whom were scanned with eyes closed in a Philips Achieva system in The Netherlands, and half of whom were scanned with eyes open in a Siemens Trio system in the UK. After pre-statistical processing and individual Independent Component Analysis (ICA), FMRIB's ICA-based X-noiseifier (FIX) was used to remove noise components from the data. GICA and dual regression were run and non-parametric statistics were used to compare spatial maps between groups before and after applying FIX. Large significant differences were found in all resting-state networks between study sites before using FIX, most of which were reduced to non-significant after applying FIX. The between-center difference in the medial/primary visual network, presumably reflecting a between-center difference in protocol, remained statistically significant. FIX helps facilitate multi-center R-fMRI research by diminishing structured noise from R-fMRI data. In doing so, it improves combination of existing data from different centers in new settings and comparison of rare diseases and risk genes for which adequate sample size remains a challenge. PMID:26578859

  3. Consulting Communities When Patients Cannot Consent: A Multi-Center Study of Community Consultation for Research in Emergency Settings

    PubMed Central

    Dickert, Neal W; Mah, Victoria A; Biros, Michelle H; Harney, Deneil M; Silbergleit, Robert; Sugarman, Jeremy; Veledar, Emir; Weinfurt, Kevin P; Wright, David W; Pentz, Rebecca D

    2013-01-01

    Objective To assess the range of responses to community consultation efforts conducted within a large network and the impact of different consultation methods on acceptance of exception from informed consent (EFIC) research and understanding of the proposed study. Design A cognitively pre-tested survey instrument was administered to 2,612 community consultation participants at 12 US centers participating in a multi-center trial of treatment for acute traumatic brain injury (TBI). Setting Survey nested within community consultation for a Phase III, randomized controlled trial of treatment for acute TBI conducted within a multi-center trial network and using EFIC. Subjects Adult participants in community consultation events. Interventions Community consultation efforts at participating sites. Measurements and Main Results Acceptance of EFIC in general, attitude toward personal EFIC enrollment, and understanding of the study content were assessed. 54% of participants agreed EFIC was acceptable in the proposed study; 71% were accepting of personal EFIC enrollment. Participants in interactive versus non-interactive community consultation events were more accepting of EFIC in general (63% vs. 49%) and personal EFIC inclusion (77% vs. 67%). Interactive community consultation participants had high-level recall of study content significantly more often than non-interactive consultation participants (77% vs. 67%). Participants of interactive consultation were more likely to recall possible study benefits (61% vs. 45%) but less likely to recall potential risks (56% vs. 69%). Conclusions Interactive community consultation methods were associated with increased acceptance of EFIC and greater overall recall of study information but lower recall of risks. There was also significant variability in EFIC acceptance among different interactive consultation events. These findings have important implications for IRBs and investigators conducting EFIC research and for community

  4. A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.

    PubMed

    Muresanu, Dafin F; Ciurea, Alexandru V; Gorgan, Radu M; Gheorghita, Eva; Florian, Stefan I; Stan, Horatiu; Blaga, Alin; Ianovici, Nicolai; Iencean, Stefan M; Turliuc, Dana; Davidescu, Horia B; Mihalache, Cornel; Brehar, Felix M; Mihaescu, Anca S; Mardare, Dinu C; Anghelescu, Aurelian; Chiparus, Carmen; Lapadat, Magdalena; Pruna, Viorel; Mohan, Dumitru; Costea, Constantin; Costea, Daniel; Palade, Claudiu; Bucur, Narcisa; Figueroa, Jesus; Alvarez, Anton

    2015-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome. PMID:25924999

  5. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry

    PubMed Central

    Evaniew, Nathan; Noonan, Vanessa K.; Fallah, Nader; Kwon, Brian K.; Rivers, Carly S.; Ahn, Henry; Bailey, Christopher S.; Christie, Sean D.; Fourney, Daryl R.; Hurlbert, R. John; Linassi, A.G.; Fehlings, Michael G.

    2015-01-01

    Abstract In prior analyses of the effectiveness of methylprednisolone for the treatment of patients with acute traumatic spinal cord injuries (TSCIs), the prognostic importance of patients' neurological levels of injury and their baseline severity of impairment has not been considered. Our objective was to determine whether methylprednisolone improved motor recovery among participants in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). We identified RHSCIR participants who received methylprednisolone according to the Second National Spinal Cord Injury Study (NASCIS-II) protocol and used propensity score matching to account for age, sex, time of neurological exam, varying neurological level of injury, and baseline severity of neurological impairment. We compared changes in total, upper extremity, and lower extremity motor scores using the Wilcoxon signed-rank test and performed sensitivity analyses using negative binomial regression. Forty-six patients received methylprednisolone and 1555 received no steroid treatment. There were no significant differences between matched participants for each of total (13.7 vs. 14.1, respectively; p=0.43), upper extremity (7.3 vs. 6.4; p=0.38), and lower extremity (6.5 vs. 7.7; p=0.40) motor recovery. This result was confirmed using a multivariate model and, as predicted, only cervical (C1–T1) rather than thoracolumbar (T2–L3) injury levels (p<0.01) and reduced baseline injury severity (American Spinal Injury Association [ASIA] Impairment Scale grades; p<0.01) were associated with greater motor score recovery. There was no in-hospital mortality in either group; however, the NASCIS-II methylprednisolone group had a significantly higher rate of total complications (61% vs. 36%; p=0.02) NASCIS-II methylprednisolone did not improve motor score recovery in RHSCIR patients with acute TSCIs in either the cervical or thoracic spine when the influence of anatomical level and severity of injury were included in the analysis. There was a significantly higher rate of total complications in the NASCIS-II methylprednisolone group. These findings support guideline recommendations against routine administration of methylprednisolone in acute TSCI. PMID:26065706

  6. Using a Validated Algorithm to Judge the Appropriateness of Total Knee Arthroplasty in the United States: A Multi-Center Longitudinal Cohort Study

    PubMed Central

    Riddle, Daniel L.; Jiranek, William A.; Hayes, Curtis W.

    2014-01-01

    Objective We used a modified version of validated appropriateness criteria to determine the prevalence rates of total knee arthroplasty (TKA) surgeries that were classified as appropriate, inconclusive or inappropriate. Based on prior evidence, we hypothesized that the prevalence of TKA surgeries classified as inappropriate would approximate 20%. Methods The appropriateness classification system was adapted for use on persons undergoing TKA in the Osteoarthritis Initiative dataset. A variety of pre-operative data were used including WOMAC Pain and Physical Function scores, radiographic and knee motion and laxity measures and age. Prevalence rates for classifications of appropriate, inconclusive and inappropriate were calculated. Results Data from 205 persons with TKA were examined. The prevalence rate was 44.0% (95%CI= 37, 51) for classifications of appropriate, 21.7% (95%CI = 16, 28) for inconclusive classifications and 34.3% (95%CI =27, 41) for inappropriate classifications. Conclusion Approximately a third of TKA surgeries were judged to be inappropriate. Variation in the characteristics of persons undergoing TKA was extensive. These data support the need for consensus development of criteria for patient selection among practitioners in the US treating potential TKA candidates. Among the important issues, consensus development needs to address variation in patient characteristics and the relative importance of pre-operative status and subsequent outcome. PMID:24974958

  7. Cognitive Dysfunction is Associated with Poor Socio-Economic Status in Patients with Cirrhosis: an International Multi-Center Study

    PubMed Central

    Bajaj, Jasmohan S; Riggio, Oliviero; Allampati, Sanath; Prakash, Ravi; Gioia, Stefania; Onori, Eugenia; Piazza, Nicole; Noble, Nicole A; White, Melanie B; Mullen, Kevin D

    2013-01-01

    Background & Aims In patients with cirrhosis, cognitive dysfunction most often results from covert hepatic encephalopathy (HE). These patients are not routinely tested for cognitive dysfunction, despite single-center evidence that it could be associated with poor socio-economic status (SES). We investigated the association between SES and cognition in a multi-center study of cirrhosis. Methods In a cross-sectional study, 236 cirrhotic patients from 3 centers (84 subjects from Virginia, 102 from Ohio, and 50 from Rome, Italy; age 57.7±8.6 y; 14% with prior overt HE) were given recommended cognitive tests and a validated SES questionnaire, which included questions about employment, personal and family income, and overall financial security. Comparisons were made among centers and between subjects who were employed or not. Regression analysis was performed using employment and personal income as outcomes. Results Only 37% of subjects had been employed in the last year. Subjects had substantial financial insecurity—their yearly personal income ranged from $16,000 to $24,999 and their family income ranged from $25,000 to $49,999. They were only able to maintain a residence for 3–6 months if their income stopped, and their current liquid assets were $500–$4999 (<$500 if debt was subtracted). Cognition and SES were worst in Ohio and best in Virginia. Cognition correlated with personal and family income, within and between centers. On regression analysis, cognitive performance (digit symbol, lures, and line tracing) was associated with personal yearly income, after controlling for demographics, country, employment, and overt HE. Unemployed subjects had a higher rate of overt HE, worse cognition, and lower personal income than employed subjects. On regression analysis, performance on digit symbol, line tracing, inhibitory control test lures, and serial dotting tests remained associated with income, similar to employment. Conclusions In an international, multi-center

  8. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study.

    PubMed

    Stewardson, Andrew J; Allignol, Arthur; Beyersmann, Jan; Graves, Nicholas; Schumacher, Martin; Meyer, Rodolphe; Tacconelli, Evelina; De Angelis, Giulia; Farina, Claudio; Pezzoli, Fabio; Bertrand, Xavier; Gbaguidi-Haore, Houssein; Edgeworth, Jonathan; Tosas, Olga; Martinez, Jose A; Ayala-Blanco, M Pilar; Pan, Angelo; Zoncada, Alessia; Marwick, Charis A; Nathwani, Dilip; Seifert, Harald; Hos, Nina; Hagel, Stefan; Pletz, Mathias; Harbarth, Stephan

    2016-08-18

    We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae. PMID:27562950

  9. Early problematic eating behaviours are associated with lower fruit and vegetable intake and less dietary variety at 4-5 years of age. A prospective analysis of three European birth cohorts.

    PubMed

    Oliveira, A; Jones, L; de Lauzon-Guillain, B; Emmett, P; Moreira, P; Charles, M A; Lopes, C

    2015-09-14

    Problematic eating behaviours during early childhood could be mediators of poor dietary habits. This study aims to prospectively relate early eating behaviours with fruit and vegetable (F&V) intake and a healthy diet variety score of children aged between 4 and 5 years. Eating behaviours were assessed in three European birth cohorts (Generation XXI from Portugal, ALSPAC from the UK and EDEN from France) at 4-6, 12-15, 24 and 48-54 months of age, based on the child's feeding difficulties, mother's perception of child's poor eating (eating small quantities at each meal, not eating enough or needing to be stimulated to eat), food refusal and difficulties in the establishment of daily food routines. Daily servings of F&V (>1 v. ≤1 serving/d, except in Generation XXI: >3 v. ≤3) and the Healthy Plate Variety Score (categorised by the median score of each sample) were calculated using FFQ. Associations were tested by logistic regressions adjusted for maternal age, education, smoking during pregnancy, any breast-feeding and the child's z-score BMI at 4-5 years of age. Children with more feeding difficulties, poor eating, food refusal/neophobia and difficulties in establishing a daily routine at 12-15, 24 and 48-54 months of age had in general lower F&V intake at 4-5 years of age. The association with vegetables was slightly stronger than with fruits. These early feeding problems were also inversely associated with the variety score at 4-5 years of age, particularly when eating behaviours were reported after 12-15 months of age. A better understanding of these early feeding difficulties may help define strategies to increase the dietary quality in children. PMID:26195187

  10. Comparison of the American-European Consensus Group Sjögren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterized sicca cohort

    PubMed Central

    Rasmussen, Astrid; Ice, John A.; Li, He; Grundahl, Kiely; Kelly, Jennifer A.; Radfar, Lida; Stone, Donald U.; Hefner, Kimberly S.; Anaya, Juan-Manuel; Rohrer, Michael; Gopalakrishnan, Rajaram; Houston, Glen D.; Lewis, David M.; Chodosh, James; Harley, John B.; Hughes, Pamela; Maier-Moore, Jacen S.; Montgomery, Courtney G.; Rhodus, Nelson L.; Farris, A. Darise; Segal, Barbara M.; Jonsson, Roland; Lessard, Christopher J.; Scofield, R. Hal; Moser Sivils, Kathy L.

    2013-01-01

    Objective To compare the performance of the American-European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome in a well-characterized sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. Methods In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. Results Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR- participants, the minor salivary gland biopsy focal score was ≥1 (74%), while 9 had positive anti-Ro/La (26%). There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. Conclusion The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available. PMID:23968620

  11. Comparison of performance of the Assessment of SpondyloArthritis International Society, the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis.

    PubMed

    Chung, Ho Yin; Lau, Chak Sing; Wu, Ka Pik; Wong, Woon Sing; MOK, Mo Yin

    2011-07-01

    Early diagnosis of spondyloarthritis (SpA) is essential as anti-tumor necrosis factor therapy can achieve significant symptomatic relief and control of disease activity. This study aims to compare the clinical characteristics, disease activity, and functional status of a Chinese cohort of SpA patients who were re-classified into ankylosing spondylitis (AS) patients fulfilling the modified New York (MNY) criteria, those with undifferentiated SpA (USpA) fulfilling the European Spondyloarthropathy Study Group (ESSG) classification criteria only (USpA/ESSG) and those who fulfill Assessment of SpondyloArthritis International Society (ASAS) only (USpA/ASAS). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), severity of morning stiffness, patient global assessment, and C-reactive protein. Functional status was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI), modified Schober index, and dimension of chest expansion. One hundred and twenty-eight patients with disease duration of 16.3 ± 10.4 years were recruited. Patients in USpA/ESSG and USpA/ASAS were significantly younger (p = 0.01), had shorter disease duration (p < 0.01), and lower BASFI (p = 0.03) than established AS patients. All three groups have active disease with comparable BASDAI >3. BASFI correlated inversely with dimension of chest expansion and negatively modified Schober index in AS patients (p < 0.01) and modestly with BASDAI (r = 0.25, p < 0.01). BASFI correlated moderately with BASDAI in USpA/ESSG (r = 0.61, p < 0.01) but not with chest expansion or modified Schober index. Compared with established AS patients recognized by MNY criteria, patients fulfilling USpA defined by ESSG or ASAS criteria had earlier disease, as active disease and less irreversible functional deficit. PMID:21336823

  12. Change in clinical indices following laser or scalpel treatment for periodontitis: A split-mouth, randomized, multi-center trial

    NASA Astrophysics Data System (ADS)

    Harris, David M.; Nicholson, Dawn M.; McCarthy, Delwin; Yukna, Raymond A.; Reynolds, Mark A.; Greenwell, Henry; Finley, James; McCawley, Thomas K.; Xenoudi, Pinelopi; Gregg, Robert H.

    2014-02-01

    Data are presented from a multi-center, prospective, longitudinal, clinical trial comparing four different treatments for periodontitis, (1) the LANAPTM protocol utilizing a FR pulsed-Nd:YAG laser; (2) flap surgery using the Modified Widman technique (MWF); (3) traditional scaling and root planing (SRP); and (4) coronal debridement (CD). Each treatment was randomized to a different quadrant. Fifty-one (54) subjects were recruited at five centers that included both private practice and university-based investigators. At 6-months and 12 months post-treatment the LANAPTM protocol and MWF yielded equivalent results based on changes in probing depths. The major difference observed between the two procedures was that patients reported significantly greater comfort following the LANAP™ procedure than following the MWF (P<0.001). There was greater reduction in bleeding in the LANAPTM quadrant than in the other three at both 6 and 12 months. Improvements following SRP were better than expected at 6 months and continued to improve, providing outcomes that were equivalent to both LANAPTM and MWF at 12 months. The improvement in the SRP quadrants suggests the hypothesis that an aspect of the LANAPTM protocol generated a significant, positive and unanticipated systemic (or trans-oral) effect on sub-gingival wound healing.

  13. Statistical Machines for Trauma Hospital Outcomes Research: Application to the PRospective, Observational, Multi-Center Major Trauma Transfusion (PROMMTT) Study

    PubMed Central

    Hubbard, Alan; Callcut, Rachael A.; Fox, Erin E.; del Junco, Deborah J.; Holcomb, John B.; Rahbar, Mohammad H.; Wade, Charles E.; Schreiber, Martin A.; Alarcon, Louis H.; Brasel, Karen J.; Bulger, Eileen M.; Cotton, Bryan A.; Muskat, Peter; Myers, John G.; Phelan, Herb A.; Cohen, Mitchell J.

    2015-01-01

    Improving the treatment of trauma, a leading cause of death worldwide, is of great clinical and public health interest. This analysis introduces flexible statistical methods for estimating center-level effects on individual outcomes in the context of highly variable patient populations, such as those of the PRospective, Observational, Multi-center Major Trauma Transfusion study. Ten US level I trauma centers enrolled a total of 1,245 trauma patients who survived at least 30 minutes after admission and received at least one unit of red blood cells. Outcomes included death, multiple organ failure, substantial bleeding, and transfusion of blood products. The centers involved were classified as either large or small-volume based on the number of massive transfusion patients enrolled during the study period. We focused on estimation of parameters inspired by causal inference, specifically estimated impacts on patient outcomes related to the volume of the trauma hospital that treated them. We defined this association as the change in mean outcomes of interest that would be observed if, contrary to fact, subjects from large-volume sites were treated at small-volume sites (the effect of treatment among the treated). We estimated this parameter using three different methods, some of which use data-adaptive machine learning tools to derive the outcome models, minimizing residual confounding by reducing model misspecification. Differences between unadjusted and adjusted estimators sometimes differed dramatically, demonstrating the need to account for differences in patient characteristics in clinic comparisons. In addition, the estimators based on robust adjustment methods showed potential impacts of hospital volume. For instance, we estimated a survival benefit for patients who were treated at large-volume sites, which was not apparent in simpler, unadjusted comparisons. By removing arbitrary modeling decisions from the estimation process and concentrating on parameters that

  14. Interaction of iron deficiency anemia and hemoglobinopathies among college students and pregnant women: a multi center evaluation in India.

    PubMed

    Mohanty, Dipika; Gorakshakar, Ajit C; Colah, Roshan B; Patel, Ramesh Z; Master, Dilip C; Mahanta, J; Sharma, Santanu K; Chaudhari, Utpal; Ghosh, Malay; Das, Sheila; Britt, Reitt P; Singh, Shawinder; Ross, Cecil; Jagannathan, Lata; Kaul, Rajni; Shukla, Deepak K; Muthuswamy, Vasantha

    2014-01-01

    Although iron deficiency anemia is very common in India, systematic large studies on the prevalence and hematological consequences of iron deficiency among carriers of β-thalassemia (β-thal) and other hemoglobinopathies are lacking. A multi center project was undertaken to screen college/university students and pregnant women for iron deficiency anemia and various hemoglobinopathies. Fifty-six thousand, seven hundred and seventy-two subjects from six states, Maharashtra, Gujarat, Karnataka, West Bengal, Assam and Punjab, were studied. Iron deficiency anemia was evaluated by measuring zinc protoporphyrin (ZPP) and hemoglobin (Hb) levels, while β-thal and other hemoglobinopathies were detected by measuring the red cell indices and by Hb analysis using high performance liquid chromatography (HPLC). College boys (2.2%), college girls (14.3%) and antenatal women (27.0%) without any hemoglobinopathies had iron deficiency anemia. Among the β-thal carriers, the prevalence of iron deficiency anemia was 17.3% in college boys, 38.1% in college girls and 55.9% in pregnant women, while in the Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] carriers, it was 7.3% in college boys, 25.4% in college girls and 78.0% in antenatal women. In individuals with Hb E disease, the prevalence of iron deficiency anemia varied from 31.2-77.3% in the three groups. A significant reduction in Hb levels was seen when iron deficiency anemia was associated with hemoglobinopathies. However, the Hb A2 levels in β-thal carriers were not greatly reduced in the presence of iron deficiency anemia. PMID:25023086

  15. Protective Effect of Dual-Strain Probiotics in Preterm Infants: A Multi-Center Time Series Analysis

    PubMed Central

    Schwab, Frank; Garten, Lars; Geffers, Christine; Gastmeier, Petra; Piening, Brar

    2016-01-01

    Objective To determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs). Design A multi-center interrupted time series analysis. Setting 44 German NICUs with routine use of dual-strain probiotics on neonatal ward level. Patients Preterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014. Intervention Routine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level. Main outcome measures Incidences of NEC, overall mortality, mortality following NEC and nosocomial BSI. Results Data from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38–0.62), overall mortality (HR = 0.60, 95% CI = 0.44–0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26–0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81–0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g. Conclusion In order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards. PMID:27332554

  16. The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study.

    PubMed

    Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

    2010-01-01

    Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies. PMID:19660557

  17. A multi-center evaluation of a powered surgical stapler in video-assisted thoracoscopic lung resection procedures in China

    PubMed Central

    Qiu, Bin; Yan, Wanpu; Chen, Keneng; Fu, Xiangning; Hu, Jian; Knippenberg, Susan; Schwiers, Michael; Kassis, Edmund; Yang, Tengfei

    2016-01-01

    Background Lung cancer is one of the most prevalent malignancies worldwide. The number of anatomic lung cancer resections performed via video-assisted thoracoscopic surgery (VATS) is growing rapidly. Staplers are widely used in VATS procedures, but there is limited clinical data regarding how they might affect performance and postoperative outcomes, including air leak. This clinical trial assessed the use of a powered stapler in VATS lung resection, with a primary study endpoint being occurrence and duration of air leak and prolonged air leak (PAL). Methods Data was collected from a single arm, multi-center study in Chinese patients receiving VATS wedge resection or lobectomy. Intra-operative data included surgery duration; cartridge selection for ligation/transection of bronchus, major vessels, and lung parenchyma; staple line interventions; blood loss; and device usage. Post-operative data included air leak assessments, chest tube duration, length of hospital stay, and adverse events (AEs). Results A total of 94 procedures across four institutions in China were included in the final analysis: 15 wedge resections, 74 lobectomies, and five wedge resections followed by lobectomies. Post-operative air leak occurred in five (5.3%) patients who had lobectomy procedures, with PAL in one (1.1%) patient. Sites were generally consistent relative to cartridge use by tissue type. The incidence of stapler firings requiring surgical interventions was seven out of 550 (1.3%). Surgeons participating in the study were satisfied with the articulation and overall usability of the stapler. Conclusions The powered staplers make the VATS procedure easier for the surgeons and have achieved intra- and post-operative patient outcomes comparable to those previously reported. PMID:27162678

  18. Blinded, multi-center validation of EEG and rating scales in identifying ADHD within a clinical sample.

    PubMed

    Snyder, Steven M; Quintana, Humberto; Sexson, Sandra B; Knott, Peter; Haque, A F M; Reynolds, Donald A

    2008-06-30

    Previous validation studies of attention deficit/hyperactivity disorder (ADHD) assessment by rating scales or EEG have provided Class-IV evidence per standards of the American Academy of Neurology. To investigate clinical applications, we collected Class-I evidence, namely from a blinded, prospective, multi-center study of a representative clinical sample categorized with a clinical standard. Participating males (101) and females (58) aged 6 to 18 had presented to one of four psychiatric and pediatric clinics because of the suspected presence of attention and behavior problems. DSM-IV diagnosis was performed by clinicians assisted with a semi-structured clinical interview. EEG (theta/beta ratio) and ratings scales (Conners Rating Scales-Revised and ADHD Rating Scales-IV) were collected separately in a blinded protocol. ADHD prevalence in the clinical sample was 61%, whereas the remainder had other childhood/adolescent disorders or no diagnosis. Comorbidities were observed in 66% of ADHD patients and included mood, anxiety, disruptive, and learning disorders at rates similar to previous findings. EEG identified ADHD with 87% sensitivity and 94% specificity. Rating scales provided sensitivity of 38-79% and specificity of 13-61%. While parent or teacher identification of ADHD by rating scales was reduced in accuracy when applied to a diverse clinical sample, theta/beta ratio changes remained consistent with the clinician's ADHD diagnosis. Because theta/beta ratio changes do not identify comorbidities or alternative diagnoses, the results do not support the use of EEG as a stand-alone diagnostic and should be limited to the interpretation that EEG may complement a clinical evaluation for ADHD. PMID:18423617

  19. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study.

    PubMed

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (> or =18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  20. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study

    PubMed Central

    Laks, Toivo; Keba, Ester; Leiner, Mariann; Merilind, Eero; Petersen, Mall; Reinmets, Sirje; Väli, Sille; Sööt, Terje; Otter, Karin

    2008-01-01

    The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (≥18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups. PMID:19337553

  1. A Multi-Center Controlled Study of the Acute and Chronic Effects of Cooling Therapy for MS

    NASA Technical Reports Server (NTRS)

    Luna, Bernadette; Schwid, Steven W.; Cutter, Gary; Murray, Ronald; Bowen, James; Pellegrino, Richard; Guisado, Raul; Webbon, Bruce W.; DeVincenzi, Donald (Technical Monitor)

    2000-01-01

    To determine the acute and chronic effects of cooling therapy on patients with MS using objective functional performance measures and self-assessed measures of fatigue. Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. Significant acute and chronic effects of cooling have not been demonstrated in a multi-center, controlled, blinded study using objective measures of neurologic function. Patients (N=84) with definite MS, mild to moderate disability (EDSS less than 6.0), and self-reported heat sensitivity were enrolled at 5 study sites. Acute effects of cooling were assessed by randomly assigning subjects to high-dose or low-dose cooling for one hour using an active cooling vest and cap (Life Enhancement Technologies, Santa Clara, CA). Settings were individualized to maintain the cooling garments at 55 F for the high-dose treatment and 70 F for the low-dose treatment. Both patients and examining investigators were blinded to treatment assignments. The MSFC and visual acuity/contrast sensitivity were assessed before and 30 minutes after treatment. The following week, subjects had an identical visit with the alternate cooling treatment. Chronic effects of cooling were assessed by randomly assigning the same subjects to unblinded daily home cooling or observation for 4 weeks. All subjects completed the Rochester Fatigue Diary (RFD) twice weekly and subjective measures of strength, cognition, and energy level daily. At the end of the period, subjects completed the Modified Fatigue Impact Scale (MFIS) and underwent another high-dose cooling session with assessment of the MSFC and vision. After a one-week washout period, subjects crossed over to the alternate 4-week treatment. Oral temperatures were reduced with both acute treatments (0.8 +/- .06 F, high and 0.5 +/- .06 F, low). While mean MSFC did not change significantly during individual cooling sessions, post hoc analysis pooling the 3 high-dose cooling sessions revealed an

  2. Variation of Community Consultation and Public Disclosure for a Pediatric Multi-centered “Exception from Informed Consent” Trial

    PubMed Central

    Holsti, Maija; Zemek, Roger; Baren, Jill; Stanley, Rachel M.; Prashant, Mahajan; Vance, Cheryl; Brown, Kathleen M.; Gonzalez, Victor; King, Denise; Jacobsen, Kammy; Shreve, Kate; van de Bruinhorst, Katrina; Jones, Anne Marie; Chamberlain, James M.

    2014-01-01

    Background The U.S. federal regulation “Exception from Informed Consent (EFIC) for Emergency Research,” 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards (IRBs) determine the adequacy of these activities at a local level. Thus there is potential for broad interpretation and practice variation. Aim To describe the variation of community consultation and public disclosure activities approved by IRBs, and the effectiveness of this process for a multi-center, EFIC, pediatric status epilepticus clinical research trial. Methods: Community consultation and public disclosure activities were analyzed for each of 15 participating sites. Surveys were conducted with participants enrolled in the status epilepticus trial to assess the effectiveness of public disclosure dissemination prior to study enrollment. Results Every IRB, among the 15 participating sites, had a varied interpretation of EFIC regulations for community consultation and public disclosure activities. IRBs required various combinations of focus groups, interviews, surveys, and meetings for community consultation; news releases, mailings, and public service announcements for public disclosure. At least 4,335 patients received information about the study from these efforts. 158 chose to be included in the “Opt Out” list. Of the 304 participants who were enrolled under EFIC, 12 (5%) had heard about the study through community consultation or public disclosure activities. The activities reaching the highest number of participants were surveys and focus groups associated with existing meetings. Public disclosure activities were more efficient and cost-effective if they were part of an in-hospital resource for

  3. Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies

    PubMed Central

    Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S.; Thwaites, David I.; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

    2016-01-01

    Abstract The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP ‘Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques’ was conducted in 2009–2012 as an extension of previously developed audit programs. Material and methods. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. Results. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Discussion. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these

  4. Knowledge of HPV and Surgery among Women Who Underwent Cervical Conization: A Korean Multi-Center Study

    PubMed Central

    Jun, So Yeun; Kim, Se Ik; Lee, Jung-Yun; Lee, San Hui; Song, Yong Jung; Chun, Kyoung-Chul; Kim, Jae Weon; Park, Sang-Yoon

    2016-01-01

    Purpose Human papillomavirus (HPV) infection is a well-known cause of cervical cancer, which, along with its precursors, can be diagnosed and treated with cervical conization (CC). This study aimed to assess HPV- and procedure-related knowledge among women who had undergone CC. Materials and Methods Between February and May 2014, consecutive women who had undergone CC at five different educational hospitals were recruited. All patients had undergone a loop electrosurgical excision procedure as the method of CC. A survey was conducted with a self-developed, 29-item questionnaire, measuring knowledge related to HPV and CC. We analyzed the responses of 160 patients who completed the questionnaire. Results Mean total knowledge scores (±standard deviation) for HPV and CC were 5.2±3.0 of a possible 13.0 and 8.3±4.2 of a possible 16.0, respectively. While 73% of the patients knew that HPV is the main cause of cervical cancer, only 44% knew that HPV is sexually transmitted. The purpose of CC was correctly identified by 71% of the patients. However, 35% failed to indicate the anatomical area resected at the time of CC in the schematic diagram. Women who were younger (p<0.001), had higher education level (p<0.001), and higher family income (p=0.008) had higher knowledge scores. In contrast, neither interval from CC to survey nor disease severity were associated with total knowledge score. Conclusion The level of knowledge related to HPV and CC was unexpectedly low in women who had undergone CC. Intuitive educational resources may improve this knowledge, and further cohort studies are warranted. PMID:27401655

  5. NCI Cohort Consortium Membership

    Cancer.gov

    The NCI Cohort Consortium membership is international and includes investigators responsible for more than 40 high-quality cohorts who are studying large and diverse populations in more than 15 different countries.

  6. Multi-center and multi-method evaluation of in vitro activities of ceftaroline against S. aureus.

    PubMed

    Koeth, Laura M; Apfalter, Petra; Becker, Karsten; Gesu, Giovanni; Martínez-Martínez, Luis; Lahiri, Sushmita D; Alm, Richard A; Ambler, Jane; Iaconis, Joseph

    2016-08-01

    This five-site study was performed to assess the reproducibility of ceftaroline MIC and disk results for Staphylococcus aureus. Three commercial broth microdilution, three gradient diffusion and ceftaroline 5μg disk diffusion methods were compared to a reference broth microdilution method against challenge isolates (n = 41) and isolates collected at four European sites (n = 30/site). For four MIC methods (Sensititre and three gradient diffusion methods), 99.0% of consolidated MIC results were within +/- 1 dilution of the reference MIC. Categorical agreement rates based on EUCAST breakpoints for the challenge isolates were 75.6-100% and for disk testing were 78.0-92.7%. There was no clear distinction between isolates with MIC results of 1 and 2mg/L with regard to variation in MIC or molecular genotyping results. The addition of an intermediate category for isolates with MIC results of 2mg/L would help to identify these isolates as borderline susceptible/non-susceptible isolates. PMID:27233426

  7. Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study

    PubMed Central

    2014-01-01

    Background The aim of this study is to investigate the inter-scan reproducibility of kinetic parameters in atherosclerotic plaque using dynamic contrast-enhanced (DCE) cardiovascular magnetic resonance (CMR) in a multi-center setting at 3T. Methods Carotid arteries of 51 subjects from 15 sites were scanned twice within two weeks on 3T scanners using a previously described DCE-CMR protocol. Imaging data with protocol compliance and sufficient image quality were analyzed to generate kinetic parameters of vessel wall, expressed as transfer constant (Ktrans) and plasma volume (vp). The inter-scan reproducibility was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CV). Power analysis was carried out to provide sample size estimations for future prospective study. Results Ten (19.6%) subjects were found to suffer from protocol violation, and another 6 (11.8%) had poor image quality (n = 6) in at least one scan. In the 35 (68.6%) subjects with complete data, the ICCs of Ktrans and vp were 0.65 and 0.28, respectively. The CVs were 25% and 62%, respectively. The ICC and CV for vp improved to 0.73 and 28% in larger lesions with analyzed area larger than 25 mm2. Power analysis based on the measured CV showed that 50 subjects per arm are sufficient to detect a 20% difference in change of Ktrans over time between treatment arms with 80% power without consideration of the dropout rate. Conclusion The result of this study indicates that quantitative measurement from DCE-CMR is feasible to detect changes with a relatively modest sample size in a prospective multi-center study despite the limitations. The relative high dropout rate suggested the critical needs for intensive operator training, optimized imaging protocol, and strict quality control in future studies. PMID:25084698

  8. European Mistletoe

    MedlinePlus

    ... gov Key References American mistletoe. Natural Medicines Comprehensive Database Web site. Accessed at www.naturaldatabase.com on July 7, 2009. European mistletoe. Natural Medicines Comprehensive Database Web site. Accessed at www.naturaldatabase.com on July ...

  9. A 6-year follow-up of a large European cohort of children with attention-deficit/hyperactivity disorder-combined subtype: outcomes in late adolescence and young adulthood.

    PubMed

    van Lieshout, Marloes; Luman, Marjolein; Twisk, Jos W R; van Ewijk, Hanneke; Groenman, Annabeth P; Thissen, Andrieke J A M; Faraone, Stephen V; Heslenfeld, Dirk J; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Rommelse, Nanda N J; Oosterlaan, Jaap

    2016-09-01

    There are very few studies on the long-term outcome of children and adolescents with ADHD-combined type in Europe. The objective of the present study is to assess the 6-year outcome (including pharmacological treatment) of a large cohort of participants with ADHD-combined type (N = 347, mean age 11.4 years) in late adolescence and early adulthood. At study entry and follow-up (mean age 17.4 years), participants were comprehensively assessed on ADHD and comorbid disorders by structured psychiatric interviews and multi-informant questionnaires. Overall functioning was assessed by the Children's Global Assessment Scale. The retention rate was 75.6 %. The majority of participants (86.5 %) persisted in a DSM-5 ADHD diagnosis, 8.4 % had a subthreshold diagnosis, and 5.1 % remitted from the disorder at follow-up. Comorbidities decreased strongly; oppositional defiant disorder: 58 > 31 %, conduct disorder: 19 > 7 %. At follow-up, mood- and anxiety disorders were virtually non-existent following strict criteria (1-3 %). Percentage of children having had pharmacological treatment at any time increased from 79 to 91 %. On the Children's Global Assessment Scale, 48.5 % of participants were still functionally impaired at follow-up. Parental ADHD, higher ADHD symptom severity at baseline and higher parent-reported impairment at baseline positively predicted current ADHD symptom severity (R (2) = 20.9 %). Younger baseline age, higher ADHD symptom severity at baseline and higher parent-reported impairment at baseline were positively associated with poorer overall functioning (R (2) = 17.8 %). Pharmacological treatment had no (beneficial) impact on either ADHD symptom severity or overall functioning. Results confirm that ADHD is largely persistent into late adolescence with severity and family history for the disorder as important risk factors. PMID:26837866

  10. Hepatitis B Virus Vaccination Coverage in Medical, Nursing, and Paramedical Students: A Cross-Sectional, Multi-Centered Study in Greece

    PubMed Central

    Papagiannis, Dimitrios; Tsimtsiou, Zoi; Chatzichristodoulou, Ioanna; Adamopoulou, Maria; Kallistratos, Ilias; Pournaras, Spyros; Arvanitidou, Malamatenia; Rachiotis, George

    2016-01-01

    Students of health professions are at high risk of hepatitis B Virus (HBV) infection during their clinical training. The aim of this cross-sectional, multi-centered study was to investigate the HBV vaccination coverage in Greek medical, nursing, and paramedical students, to look into their attitudes towards the importance of vaccines and to reveal reasons associated with not being vaccinated. A self-completed, anonymous questionnaire was distributed to 2119 students of health professions in Greece, during the academic year 2013–2014. The HBV vaccination coverage of students was high (83%), being higher among medical students (88.1%, vs. 81.4% among nursing and 80.1% among paramedical students; p < 0.001). The vast majority of them (95%) have been vaccinated during childhood. In addition, 30% of the unvaccinated students declared fear over HBV safety. Our results indicate that the healthcare students achieved higher reported immunization rates compared to the currently serving healthcare workers, but also to the students of the last decade. The fact that nursing and paramedical students have lower coverage figures underlines the importance of targeted interventions for the different subgroups of healthcare students in terms of educational programs and screening for HBV markers in order to increase HBV vaccination uptake. PMID:26999171

  11. The Development of the Multi-Center Traffic Management Advisor (MCTMA): Traffic Flow Management Research in a Multi-Facility Environment

    NASA Technical Reports Server (NTRS)

    Lee, Katharine K.; Davis, Thomas J.; Levin, Kerry M.; Rowe, Dennis W.

    2001-01-01

    The Traffic Management Advisor (TMA) is a decision-support tool for traffic managers and air traffic controllers that provides traffic flow visualization and other flow management tools. TMA creates an efficiently sequenced and safely spaced schedule for arrival traffic that meets but does not exceed specified airspace system constraints. TMA is being deployed at selected facilities throughout the National Airspace System in the US as part of the FAA's Free Flight Phase 1 program. TMA development and testing, and its current deployment, focuses on managing the arrival capacity for single major airports within single terminal areas and single en route centers. The next phase of development for this technology is the expansion of the TMA capability to complex facilities in which a terminal area or airport is fed by multiple en route centers, thus creating a multicenter TMA functionality. The focus of the multi-center TMA (McTMA) development is on the busy facilities in the Northeast comdor of the US. This paper describes the planning and development of McTMA and the challenges associated with adapting a successful traffic flow management tool for a very complex airspace.

  12. The Relationship Between Distance to Water Source and Moderate-to-Severe Diarrhea in the Global Enterics Multi-Center Study in Kenya, 2008-2011.

    PubMed

    Nygren, Benjamin L; O'Reilly, Ciara E; Rajasingham, Anangu; Omore, Richard; Ombok, Maurice; Awuor, Alex O; Jaron, Peter; Moke, Fenny; Vulule, John; Laserson, Kayla; Farag, Tamer H; Nasrin, Dilruba; Nataro, James P; Kotloff, Karen L; Levine, Myron M; Derado, Gordana; Ayers, Tracy L; Lash, R Ryan; Breiman, Robert F; Mintz, Eric D

    2016-05-01

    In the developing world, fetching water for drinking and other household uses is a substantial burden that affects water quantity and quality in the household. We used logistic regression to examine whether reported household water fetching times were a risk factor for moderate-to-severe diarrhea (MSD) using case-control data of 3,359 households from the Global Enterics Multi-Center Study in Kenya in 2009-2011. We collected additional global positioning system (GPS) data for a subset of 254 randomly selected households and compared GPS-based straight line and actual travel path distances to fetching times reported by respondents. GPS-based data were highly correlated with respondent-provided times (Spearman correlation coefficient = 0.81, P < 0.0001). The median estimated one-way distance to water source was 200 m for cases and 171 for controls (Wilcoxon rank sums/Mann-Whitney P = 0.21). A round-trip fetching time of > 30 minutes was reported by 25% of cases versus 15% of controls and was significantly associated with MSD where rainwater was not used in the last 2 weeks (odds ratio = 1.97, 95% confidence interval = 1.56-2.49). These data support the United Nations definition of access to an improved water source being within 30 minutes total round-trip travel time. PMID:26928833

  13. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial

    PubMed Central

    2014-01-01

    Background Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. Methods The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. Discussion As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. Trial registration NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013. Recruiting. Randomisation commenced on 1 January 2014. PMID:24661817

  14. Hepatitis B Virus Vaccination Coverage in Medical, Nursing, and Paramedical Students: A Cross-Sectional, Multi-Centered Study in Greece.

    PubMed

    Papagiannis, Dimitrios; Tsimtsiou, Zoi; Chatzichristodoulou, Ioanna; Adamopoulou, Maria; Kallistratos, Ilias; Pournaras, Spyros; Arvanitidou, Malamatenia; Rachiotis, George

    2016-03-01

    Students of health professions are at high risk of hepatitis B Virus (HBV) infection during their clinical training. The aim of this cross-sectional, multi-centered study was to investigate the HBV vaccination coverage in Greek medical, nursing, and paramedical students, to look into their attitudes towards the importance of vaccines and to reveal reasons associated with not being vaccinated. A self-completed, anonymous questionnaire was distributed to 2119 students of health professions in Greece, during the academic year 2013-2014. The HBV vaccination coverage of students was high (83%), being higher among medical students (88.1%, vs. 81.4% among nursing and 80.1% among paramedical students; p < 0.001). The vast majority of them (95%) have been vaccinated during childhood. In addition, 30% of the unvaccinated students declared fear over HBV safety. Our results indicate that the healthcare students achieved higher reported immunization rates compared to the currently serving healthcare workers, but also to the students of the last decade. The fact that nursing and paramedical students have lower coverage figures underlines the importance of targeted interventions for the different subgroups of healthcare students in terms of educational programs and screening for HBV markers in order to increase HBV vaccination uptake. PMID:26999171

  15. The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

    PubMed Central

    Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2014-01-01

    Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

  16. European Community.

    PubMed

    1987-05-01

    The European Community was established in 1951 to reconcile France and Germany after World War II and to make possible the eventual federation of Europe. By 1986, there were 12 member countries: France, Italy, Belgium, the Federal Republic of Germany, Luxembourg, the Netherlands, Denmark, Ireland, the United Kingdom, Greece, Spain, and Portugal. Principal areas of concern are internal and external trade, agriculture, monetary coordination, fisheries, common industrial and commercial policies, assistance, science and research, and common social and regional policies. The European Community has a budget of US$34.035 billion/year, funded by customs duties and 1.4% of each member's value-added tax. The treaties establishing the European Community call for members to form a common market, a common customs tariff, and common agricultural, transport, economic, and nuclear policies. Major European Community institutions include the Commission, Council of Ministers, European Parliament, Court of Justice, and Economic and Social Committee. The Community is the world's largest trading unit, accounting for 15% of world trade. The 2 main goals of the Community's industrial policy are to create an open internal market and to promote technological innovation in order to improve international competitiveness. The European Community aims to contribute to the economic and social development of Third World countries as well. PMID:12177941

  17. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

    PubMed

    Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M; Culverhouse, Robert C; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N; Maher, Brion S; Melroy, Whitney E; Nelson, Elliot C; Reid, Mark W; Robinson, Jason D; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A; Cannon, Dale S; Cichon, Sven; Corley, Robin P; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J; Grucza, Richard A; Hardin, Jill; Hartmann, Annette M; Heath, Andrew C; Herms, Stefan; Hodgkinson, Colin A; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O; Johnstone, Elaine; Kaneva, Radka P; Kendler, Kenneth S; Kiefer, Falk; Kranzler, Henry R; Krauter, Ken S; Levran, Orna; Lucae, Susanne; Lynskey, Michael T; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G; Mattheisen, Manuel; Montgomery, Grant W; Müller-Myhsok, Bertram; Murphy, Michael F; Neale, Michael C; Nikolov, Momchil A; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W; Chen, Jingchun; Cinciripini, Paul M; Edenberg, Howard J; Ehringer, Marissa A; Ferrell, Robert E; Gelernter, Joel; Goldman, David; Hewitt, John K; Hopfer, Christian J; Iacono, William G; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M; Madden, Pamela A F; McGue, Matt; Munafò, Marcus R; Philibert, Robert A; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T; Swan, Gary E; Todorov, Alexandre A; Vanyukov, Michael M; Weiss, Robert B; Bierut, Laura J; Saccone, Nancy L

    2016-03-01

    The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. PMID:26392368

  18. Cohort profile: UK Millennium Cohort Study (MCS).

    PubMed

    Connelly, Roxanne; Platt, Lucinda

    2014-12-01

    The UK Millennium Cohort Study (MCS) is an observational, multidisciplinary cohort study that was set up to follow the lives of children born at the turn of the new century. The MCS is nationally representative and 18 552 families (18 827 children) were recruited to the cohort in the first sweep. There have currently been five main sweeps of data collection, at ages 9 months and 3, 5, 7 and 11 years. A further sweep of data collection is planned for age 14 years. A range of health-related data have been collected as well as measures concerning child development, cognitive ability and educational attainment. The data also include a wealth of information describing the social, economic and demographic characteristics of the cohort members and their families. In addition, the MCS data have been linked to administrative data resources including health records. The MCS provides a unique and valuable resource for the analysis of health outcomes and health inequalities. The MCS data are freely available to bona fide researchers under standard access conditions via the UK Data Service (http://ukdataservice.ac.uk) and the MCS website provides detailed information on the study (http://www.cls.ioe.ac.uk/mcs). PMID:24550246

  19. High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: results from the European Prospective Investigation into Cancer and Nutrition–Oxford study☆☆☆

    PubMed Central

    Sobiecki, Jakub G.; Appleby, Paul N.; Bradbury, Kathryn E.; Key, Timothy J.

    2016-01-01

    The aim of this study was to investigate differences in dietary intakes between 30 251 participants in the European Prospective Investigation into Cancer and Nutrition–Oxford study, comprising 18 244 meat eaters, 4 531 fish eaters, 6 673 vegetarians, and 803 vegans aged 30 to 90 years who completed semiquantitative food frequency questionnaires. We hypothesized that these groups characterized by varying degrees of animal product exclusion have significantly different intakes of many nutrients, with possible implications for dietary adequacy and compliance with population dietary goals. Nutrient intakes were estimated including fortification in foods, but excluding dietary supplements. Dietary supplementation practices were also evaluated. Highly significant differences were found in estimated nutrient intakes between meat eaters and vegans, with fish eaters and vegetarians usually having intermediate values. Meat eaters had the highest energy intakes, followed by fish eaters and vegetarians, whereas vegans had the lowest intakes. Vegans had the highest intakes of polyunsaturated fatty acids, dietary fiber, vitamins C and E, folate, magnesium, iron, and copper. Meat eaters had the highest intake of saturated fatty acids, protein, vitamin B2, vitamin B12, vitamin D, zinc, and iodine. Fish eaters had the highest intakes of calcium and selenium. There were no statistically significant differences in sodium and potassium intakes between dietary groups. With the exception of sodium intake, compliance with population dietary goals was high across diet groups. The results suggested a high prevalence of inadequacy for dietary vitamin B12 and iodine in vegans. The diet groups under study showed striking differences in dietary intakes, with possible implications for compliance with dietary recommendations, as well as cardiometabolic diseases risk. PMID:27101764

  20. High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: results from the European Prospective Investigation into Cancer and Nutrition-Oxford study.

    PubMed

    Sobiecki, Jakub G; Appleby, Paul N; Bradbury, Kathryn E; Key, Timothy J

    2016-05-01

    The aim of this study was to investigate differences in dietary intakes between 30251 participants in the European Prospective Investigation into Cancer and Nutrition-Oxford study, comprising 18 244 meat eaters, 4 531 fish eaters, 6 673 vegetarians, and 803 vegans aged 30 to 90 years who completed semiquantitative food frequency questionnaires. We hypothesized that these groups characterized by varying degrees of animal product exclusion have significantly different intakes of many nutrients, with possible implications for dietary adequacy and compliance with population dietary goals. Nutrient intakes were estimated including fortification in foods, but excluding dietary supplements. Dietary supplementation practices were also evaluated. Highly significant differences were found in estimated nutrient intakes between meat eaters and vegans, with fish eaters and vegetarians usually having intermediate values. Meat eaters had the highest energy intakes, followed by fish eaters and vegetarians, whereas vegans had the lowest intakes. Vegans had the highest intakes of polyunsaturated fatty acids, dietary fiber, vitamins C and E, folate, magnesium, iron, and copper. Meat eaters had the highest intake of saturated fatty acids, protein, vitamin B2, vitamin B12, vitamin D, zinc, and iodine. Fish eaters had the highest intakes of calcium and selenium. There were no statistically significant differences in sodium and potassium intakes between dietary groups. With the exception of sodium intake, compliance with population dietary goals was high across diet groups. The results suggested a high prevalence of inadequacy for dietary vitamin B12 and iodine in vegans. The diet groups under study showed striking differences in dietary intakes, with possible implications for compliance with dietary recommendations, as well as cardiometabolic diseases risk. PMID:27101764

  1. Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study.

    PubMed

    Hasserius, R; Karlsson, M K; Nilsson, B E; Redlund-Johnell, I; Johnell, O

    2003-01-01

    The aim of this study was to evaluate whether a prevalent vertebral deformity predicts mortality and fractures in both men and women. In the city of Malmö, 598 individuals (298 men, 300 women; age 50-80 years) were selected from the city's population and were included in the Swedish part of the European Vertebral Osteoporosis Study (EVOS). At baseline the participants answered a questionnaire and lateral spine radiographs were performed. The prevalence of subjects with vertebral deformity was assessed using a morphometric method. The mortality during a 10-year follow-up period was determined through the register of the National Swedish Board of Health and Welfare. Eighty-five men and 43 women died during the study period. The subsequent fracture incidence during the follow-up period was ascertained by postal questionnaires, telephone interviews and by a survey of the archives of the Department of Radiology in the city hospital. Thirty-seven men and 69 women sustained a fracture during the study period. Data are presented as hazard ratios (HR) with 95% confidence interval (95% CI) within brackets. Prevalent vertebral deformity, defined as a reduction by more than 3 standard deviations (SD) in vertebral height ratio, predicted mortality during the forthcoming decade in both men [age-adjusted HR 2.4 (95% CI 1.6-3.9)] and women [age-adjusted HR 2.3 (95% CI 1.3-4.3)]. In men there was an increased mortality due to cardiovascular and pulmonary diseases and in women due to cancer. Prevalent vertebral deformity predicted an increased risk of any fracture during the forthcoming decade in both men [age-adjusted HR 2.7 (95% CI 1.4-5.3)] and women [age-adjusted HR 1.8 (95% CI 1.1-2.9)]. Prevalent vertebral deformity predicted an increased risk of any subsequent fragility fracture in women [age-adjusted HR 2.0 (95% CI 1.1-3.5)]; however, in men the increased risk was nonsignificant [age-adjusted HR 1.9 (95% CI 0.7-5.1)]. In summary, a prevalent vertebral deformity can predict

  2. Diagnosis, Clinical Course, and 1-Year Outcome in Patients Hospitalized for Heart Failure With Preserved Ejection Fraction (from the Polish Cohort of the European Society of Cardiology Heart Failure Long-Term Registry).

    PubMed

    Kapłon-Cieślicka, Agnieszka; Tymińska, Agata; Peller, Michał; Balsam, Paweł; Ozierański, Krzysztof; Galas, Michalina; Marchel, Michał; Crespo-Leiro, Maria G; Maggioni, Aldo Pietro; Drożdż, Jarosław; Filipiak, Krzysztof J; Opolski, Grzegorz

    2016-08-15

    Compared with heart failure (HF) with reduced ejection fraction (HF-REF), the diagnosis of HF with preserved EF (HF-PEF) is more challenging. The aim of the study was to assess the prevalence of HF-PEF among patients hospitalized for HF, to evaluate the pertinence of HF-PEF diagnosis and to compare HF-PEF and HF-REF patients with respect to outcomes. The analysis included 661 Polish patients hospitalized for HF, selected from the European Society of Cardiology (ESC)-HF Long-Term Registry. Patients with an EF of ≥50% were included in the HF-PEF group and patients with an EF of <50% - in the HF-REF group. The primary end point was all-cause death at 1 year. The secondary end point was a composite of all-cause death and rehospitalization for HF at 1 year. HF-PEF was present in 187 patients (28%). Of those 187 patients, mitral inflow pattern was echocardiographically assessed in 116 patients (62%) and classified as restrictive/pseudonormal in 37 patients (20%). Compared with HF-REF subjects, patients with HF-PEF were older, more often female, and had a higher prevalence of hypertension, atrial fibrillation and sleep apnea. Despite lower B-type natriuretic peptide concentrations and lower prevalence of moderate-to-severe mitral regurgitation in patients with HF-PEF, congestive symptoms at admission were as severe as in patients with HF-REF. There were no significant differences in in-hospital mortality between the HF groups. One-year mortality was high in both groups (17% in HF-PEF vs 21% in HF-REF, p = 0.22). There was a trend toward a lower frequency of the secondary end point in the HF-PEF group (32% vs 40%, p = 0.07). In conclusion, in clinical practice, even easily obtainable echocardiographic indexes of diastolic dysfunction are relatively rarely acquired. One-year survival rate of patients with HF-PEF is not significantly better than that of patients with HF-REF. PMID:27374606

  3. Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial.

    PubMed

    Hifumi, Toru; Kuroda, Yasuhiro; Kawakita, Kenya; Yamashita, Susumu; Oda, Yasutaka; Dohi, Kenji; Maekawa, Tsuyoshi

    2016-06-01

    In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4). PMID:26413933

  4. Management of Adult Chronic Immune Thrombocytopenia in Japan: Patient and Hematologist Perspectives from a Multi-center Cross-sectional Questionnaire Survey.

    PubMed

    Tsukune, Yutaka; Komatsu, Norio

    2016-01-01

    Objective The objective of this study was to explore the perspective of hematologists and their patients regarding the management of adult chronic immune thrombocytopenia (ITP). Methods This was a multi-center, questionnaire-based, cross-sectional study conducted between 2012 and 2013 throughout Japan. Patients Hematologists, members of the Japanese Society of Hematology in 171 institutions, and their patients were invited to participate in this study. The hematologists were mainly asked about their treatment strategies, while patients were asked about their opinion of the applied treatments, treatment effect, impact on their quality of life (QOL), and treatment satisfaction. Results Questionnaires from 204 hematologists and 213 patients were collected. One hundred sixty hematologists (78.4%) started treatment based on the patient's platelet count. Corticosteroids were considered to be the most effective treatment (44.1%). Forty-six percent of hematologists responded that treatment would be started after the platelet count fell below 20×10(9)/L with bleeding symptoms, compared to 62.9% for patients with no bleeding symptoms. A platelet count of 50×10(9)/L or lower was acceptable for 94.0% of hematologists and 66.8% of patients. Fatigue was most frequently experienced by patients (44.6%). Patients also experienced psychological symptoms (feeling of anxiety or depressive mood: 29.1%, labyrinthitis: 23.5%). While 70.6% of hematologists assumed that the patient QOL was impaired to a moderate to substantial degree, the QOL was impaired in 34.3% of patients. Conclusion A substantial gap which exists between hematologists and their patients highlights a need for better understanding of potential conflicts for establishing effective strategies for ITP management. PMID:27580537

  5. Impaired visual fixation at age 2 years in children born before the 28th week of gestation. Antecedents and correlates in the multi-center ELGAN Study

    PubMed Central

    Phadke, Anuradha; Msall, Michael E; Droste, Patrick; Allred, Elizabeth N; O'Shea, T. Michael; Kuban, Karl; Dammann, Olaf; Leviton, Alan

    2014-01-01

    Background Very little is known about the prevalence, antecedents and correlates of impaired visual fixation in former very preterm newborns. Methods In the multi-center ELGAN Study sample of 1057 infants born before the 28th week of gestation who had a developmental assessment at 2 years corrected age, we identified 73 who were unable to follow an object across the midline. We compared them to the 984 infants who could follow an object across the midline. Results In this sample of very preterm newborns, those who had impaired visual fixation were much more likely than those without impaired visual fixation to have been born after the shortest of gestations (odds ratio = 3.2; 99% confidence interval =1.4, 7.5) and exposed to maternal aspirin (OR: 5.2; 99% CI: 2.2, 12). They were also more likely than their peers to have had prethreshold ROP (OR: 4.1; 99% CI: 1.8, 9.0). At age 2 years, the children with impaired fixation were more likely than others to be unable to walk (even with assistance) (OR: 7.5; 99% CI: 2.2, 26) and have a Mental Development Index more than 3 standard deviations below the mean of a normative sample (OR:3.6; 99% CI: 1.4, 8.2). Conclusion Risk factors for brain and retinal damage, such as very low gestational age, appear to be risk factors for impaired visual fixation. This inference is further supported by the co-occurrence at age 2 years of impaired visual fixation, inability to walk, and a very low Mental Development Index PMID:24938138

  6. Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse.

    PubMed

    Jongen, Peter Joseph; Stavrakaki, Ioanna; Voet, Bernard; Hoogervorst, Erwin; van Munster, Erik; Linssen, Wim H; Sinnige, Ludovicus G; Verhagen, Wim I; Visser, Leo H; van der Kruijk, Ruud; Verheul, Freek; Boringa, Jan; Heerings, Marco; Gladdines, Werner; Lönnqvist, Fredrik; Gaillard, Pieter

    2016-08-01

    In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-report questionnaires stating IVMP's most common AEs were completed at baseline, the 2nd day of treatment, and 1 day and 1 week after treatment. Eighty-five patients were included, 66 completed the baseline questionnaire, and 59 completed at least one post-baseline questionnaire. Patients reported on average 4 (median) AEs; two (3.4 %) reported no AE. Most frequent was change in taste (61 %), facial flushing (61 %), sick/stomach pain (53 %), sleep disturbance (44 %), appetite change (37 %), agitation (36 %), and behavioral changes (36 %). Of all AEs, 34.3 % were severe and 37.9 % impacted on ADL. A 3-day course resulted in 4 (median) AEs and a 5-day course in 7. All patients with high disease impact had two or more AEs, compared with 79 % of those with low impact (p < 0.01). Of patients with high disability, 45 % had severe AEs, compared with 16 % of those with low disability. Severe central nervous system (CNS)-related AEs occurred two times more frequently in patients with high disease impact, and two-and-a-half times more frequently in patients with high disability. Therefore, in virtually all patients, high-dose IVMP leads to AEs, with about one of three AEs being severe with impact on ADL. Patients with high disease impact or high disability may experience more (severe) AEs, due to a higher occurrence of severe CNS-related AEs. PMID:27272956

  7. Multi-center evaluation of the novel fully-automated PCR-based Idylla™ BRAF Mutation Test on formalin-fixed paraffin-embedded tissue of malignant melanoma.

    PubMed

    Melchior, Linea; Grauslund, Morten; Bellosillo, Beatriz; Montagut, Clara; Torres, Erica; Moragón, Ester; Micalessi, Isabel; Frans, Johan; Noten, Veerle; Bourgain, Claire; Vriesema, Renske; van der Geize, Robert; Cokelaere, Kristof; Vercooren, Nancy; Crul, Katrien; Rüdiger, Thomas; Buchmüller, Diana; Reijans, Martin; Jans, Caroline

    2015-12-01

    The advent of BRAF-targeted therapies led to increased survival in patients with metastatic melanomas harboring a BRAF V600 mutation (implicated in 46-48% of malignant melanomas). The Idylla(™) System (Idylla(™)), i.e., the real-time-PCR-based Idylla(™) BRAF Mutation Test performed on the fully-automated Idylla(™) platform, enables detection of the most frequent BRAF V600 mutations (V600E/E2/D, V600K/R/M) in tumor material within approximately 90 min and with 1% detection limit. Idylla(™) performance was determined in a multi-center study by analyzing BRAF mutational status of 148 archival formalin-fixed paraffin-embedded (FFPE) tumor samples from malignant melanoma patients, and comparing Idylla(™) results with assessments made by commercial or in-house routine diagnostic methods. Of the 148 samples analyzed, Idylla(™) initially recorded 7 insufficient DNA input calls and 15 results discordant with routine method results. Further analysis learned that the quality of 8 samples was insufficient for Idylla(™) testing, 1 sample had an invalid routine test result, and Idylla(™) results were confirmed in 10 samples. Hence, Idylla(™) identified all mutations present, including 7 not identified by routine methods. Idylla(™) enables fully automated BRAF V600 testing directly on FFPE tumor tissue with increased sensitivity, ease-of-use, and much shorter turnaround time compared to existing diagnostic tests, making it a tool for rapid, simple and highly reliable analysis of therapeutically relevant BRAF mutations, in particular for diagnostic units without molecular expertise and infrastructure. PMID:26407762

  8. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma

    PubMed Central

    Brown, Nicholas; McBain, Catherine; Nash, Stephen; Hopkins, Kirsten; Sanghera, Paul; Saran, Frank; Phillips, Mark; Dungey, Fiona; Clifton-Hadley, Laura; Wanek, Katharina; Krell, Daniel; Jeffries, Sarah; Khan, Iftekhar; Smith, Paul; Mulholland, Paul

    2016-01-01

    Background Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. Methods and Findings This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Conclusions Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. Trial Registration ClinicalTrials.gov NCT01310855 PMID:27232884

  9. Six-month healing success rates after endodontic treatment using the novel GentleWave™ System: The pure prospective multi-center clinical study

    PubMed Central

    Le, Khang T.; Woo, Stacey M.; Rassoulian, Shahriar A.; McLachlan, Kimberly; Abbassi, Farah; Garland, Randy W.

    2016-01-01

    Background This prospective multi-center (PURE) clinical study evaluated healing rates for molars after root canal treatment employing the GentleWave® System (Sonendo, Inc., Laguna Hills, CA). Material and Methods Eighty-nine patients met the inclusion criteria and consented for this clinical study after referral for a root canal treatment. All enrolled patients were treated with the GentleWave System. Five endodontists performed the clinical procedures and follow-up evaluations. Pre-operative, intra-operative, and post-operative data were collected from the consented patients. Each patient was evaluated for clinical signs and symptoms. Two trained, blinded, and independent evaluators scored the subject tooth radiographs for apical periodontitis using the periapical index (PAI). The teeth classified as healing or healed were considered as a success and composed of a cumulative success rate of healing. Statistical analysis was performed by using the Fisher’s exact test, Pearson correlation, and multivariate logistic regression analyses of the pre-operative prognostic factors at 0.05 significance level. Results Seventy-seven patients were evaluated at six months with a follow-up rate of 86.5%. The cumulative success rate of healing was 97.4%. Eleven prognostic factors were identified using bivariate analyses. Using logistic analyses, the two prognostic significant variables that were directly correlated to healing were the pre-operative presence of periapical index (p value=0.016), and single treatment visits (p value=0.024). Conclusions In this six-month PURE clinical study, the cumulative success rate of healing was 97.4% when patients were treated with the GentleWave® System. Key words:Healing rate, root canal treatment, molar, GentleWave™, Sonendo®, Multisonic Ultracleaning™ . PMID:27398180

  10. Cancer Epidemiology Cohorts

    Cancer.gov

    Cohort studies are fundamental for epidemiological research by helping researchers better understand the etiology of cancer and provide insights into the key determinants of this disease and its outcomes.

  11. Public perceptions of cohort studies and biobanks in Germany.

    PubMed

    Starkbaum, Johannes; Gottweis, Herbert; Gottweis, Ursula; Kleiser, Christina; Linseisen, Jakob; Meisinger, Christa; Kamtsiuris, Panagiotis; Moebus, Susanne; Jöckel, Karl-Heinz; Börm, Sonja; Wichmann, H-Erich

    2014-04-01

    Cohort studies and biobank projects have led to public discussions in several European countries in the past. In Germany, many medium-sized studies are currently running successfully in terms of respondent rates. However, EU-wide research on general public perceptions of biobanks and cohort studies have shown that Germany is among those countries where people express the highest reluctance for providing body material and other data for research purposes. Because of early efforts of the just-initiated German National Cohort Study, we are able to begin to investigate in greater detail how various groups of people across Germany reflect and discuss the ongoing implementation of cohort studies and biobanking in Germany. Our research is based on 15 focus group discussions in four German regions, as well as on Eurobarometer poll data on biobanking. PMID:24749879

  12. The design and rationale of a multi-center clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT)

    PubMed Central

    2014-01-01

    Background High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. Purpose To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. Methods SPRINT is a multi-center, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. SPRINT recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first occurrence of a myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease

  13. Progress in Multi-Center Probabilistic Wave Forecasting and Ensemble-Based Data Assimilation using LETKF at the US National Weather Service

    NASA Astrophysics Data System (ADS)

    Alves, Jose-Henrique; Bernier, Natacha; Etala, Paula; Wittmann, Paul

    2015-04-01

    The combination of ensemble predictions of Hs made by the US National Weather Service (NEW) and the US Navy Fleet Numerical Meteorological and Oceanography Center (FNMOC) has established the NFCENS, a probabilistic wave forecast system in operations at NCEP since 2011. Computed from 41 combined wave ensemble members, the new product outperforms deterministic and probabilistic forecasts and nowcasts of Hs issued separately at each forecast center, at all forecast ranges. The successful implementation of the NFCENS has brought new opportunities for collaboration with Environment Canada (EC). EC is in the process of adding new global wave model ensemble products to its existing suite of operational regional products. The planned upgrade to the current NFCENS wave multi-center ensemble includes the addition of 20 members from the Canadian WES. With this upgrade, the NFCENS will be renamed North American Wave Ensemble System (NAWES). As part of the new system implementation, new higher-resolution grids and upgrades to model physics using recent advances in source-term parameterizations are being tested. We provide results of a first validation of NAWES relative to global altimeter data, and buoy measurements of waves, as well as its ability to forecast waves during the 2012 North Atlantic hurricane Sandy. A second line of research involving wave ensembles at the NWS is the implementation of a LETKF-based data assimilation system developed in collaboration with the Argentinian Navy Meteorological Service. The project involves an implementation of the 4D-LETKF in the NWS global wave ensemble forecast system GWES. The 4-D scheme initializes a full 81-member ensemble in a 6-hour cycle. The LETKF determines the analysis ensemble locally in the space spanned by the ensemble, as a linear combination of the background perturbations. Observations from three altimeters and one scatterometer were used. Preliminary results for a prototype system running at the NWS, including

  14. THE ASSOCIATION BETWEEN PHYSIOLOGIC DEAD-SPACE FRACTION AND MORTALITY IN PATIENTS WITH THE ACUTE RESPIRATORY DISTRESS SYNDROME ENROLLED INTO A PROSPECTIVE MULTI-CENTERED CLINICAL TRIAL

    PubMed Central

    Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D.; Calfee, Carolyn S.; Matthay, Michael A

    2014-01-01

    Objective To test the association between pulmonary dead-space fraction (VD/VT) and mortality in patients with ARDS (Berlin Definition, PaO2/FiO2 ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. Design Prospective, multi-center study. Setting Medical-surgical intensive care units in the United States. Subjects 126 ALI patients enrolled into a phase III randomized, placebo-controlled study of aerosolized albuterol. Interventions None Measurements and Main Results VD/VT and pulmonary mechanics were measured within 4 hours of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend towards higher VD/VT compared to survivors (0.62 ± 0.11 vs. 0.56 ± 0.11 respectively, p = 0.08). Differences in VD/VT between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs. 0.55 ± 0.11 respectively, p = 0.01) and 2 (0.67 ± 0.12 vs. 0.56 ± 0.11 respectively, p=0.004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in VD/VT [95% confidence interval]: 6.84 [1.62–28.84] p = 0.01; and study day 2: 4.90 [1.28–18.73] p = 0.02) after adjusting for VD/VT, PaO2/FiO2, oxygenation index, vasopressor use and the primary risk for ARDS. Using a Cox proportional hazard model, VD/VT was associated with a trend towards higher mortality (HR = 4.37 [CI: 0.99 – 19.32]; p = 0.052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI: 1.12 – 3.35] p = 0.04). Conclusions Markedly elevated VD/VT (≥ 0.60) in early ARDS is associated with higher mortality. Measuring VD/VT may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. PMID:24381187

  15. Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

    PubMed Central

    de Vos, Alexander M; Rutten, Annemarieke; van de Zaag-Loonen, Hester J; Bots, Michiel L; Dikkers, Riksta; Buiskool, Robert A; Mali, Willem P; Lubbers, Daniel D; Mosterd, Arend; Prokop, Mathias; Rensing, Benno J; Cramer, Maarten J; van Es, H Wouter; Moll, Frans L; van de Pavoordt, Eric D; Doevendans, Pieter A; Velthuis, Birgitta K; Mackaay, Albert J; Zijlstra, Felix; Oudkerk, Matthijs

    2008-01-01

    Background Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about

  16. A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. Via the inhibition of inflammatory reactions and of apoptosis, stem cell recruitment, advancement of angiogenesis and growth factor release, EPO enhances healing and thus restitutio ad integrum after trauma. Human skin contains EPO receptors and is able to synthesize EPO. We therefore hypothesize that EPO is able to optimize wound healing in thermally injured patients. Methods/Design This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. Discussion We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. Trial registration EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT

  17. A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto™ (fluralaner) against Frontline™ (fipronil) in flea- and tick-infested dogs

    PubMed Central

    2014-01-01

    Background Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs. Methods A randomized, investigator-blinded, multi-centered field study compared the flea- and tick-control efficacy for dogs over a 12-week period with either a single oral dose of Bravecto™ (fluralaner) formulated as a chewable tablet or with three sequential topical Frontline™ (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto™ (fluralaner) and 54 tick-infested dogs were treated with Frontline™ (fipronil). Dogs in 115 flea-infested households received Bravecto™ (fluralaner) and dogs in 61 flea-infested households received Frontline™ (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tick-free and flea-free households were determined. Results At weeks 2, 4, 8, and 12, Bravecto™ (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline™ (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto™ (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and Frontline™ (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline™ (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion. Conclusions

  18. Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study

    PubMed Central

    Ni, Zhaohui; Zhong, Yifei; Qi, Yinghui; Shao, Xinghua; Wang, Qin; Cao, Liou; Zhang, Minfang; Xie, Yuanyuan; Qi, Chaojun; Tian, Lei; Mou, Shan

    2015-01-01

    Background and Objectives Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored. Design and Patients Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study. Results Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort. Conclusions This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse. PMID:26371477

  19. Occupational Cohort Time Scales

    PubMed Central

    Roth, H. Daniel

    2015-01-01

    Purpose: This study explores how highly correlated time variables (occupational cohort time scales) contribute to confounding and ambiguity of interpretation. Methods: Occupational cohort time scales were identified and organized through simple equations of three time scales (relational triads) and the connections between these triads (time scale web). The behavior of the time scales was examined when constraints were imposed on variable ranges and interrelationships. Results: Constraints on a time scale in a triad create high correlations between the other two time scales. These correlations combine with the connections between relational triads to produce association paths. High correlation between time scales leads to ambiguity of interpretation. Conclusions: Understanding the properties of occupational cohort time scales, their relational triads, and the time scale web is helpful in understanding the origins of otherwise obscure confounding bias and ambiguity of interpretation. PMID:25647318

  20. Associations between smoking and caffeine consumption in two European cohorts

    PubMed Central

    Taylor, Amy E.; Ware, Jennifer J.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Willemsen, Gonneke; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

    2016-01-01

    Abstract Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self‐reported smoking behaviour and caffeine consumption. Setting Adults from the general population in the Netherlands and the United Kingdom. Participants Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). Measurements Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. Findings After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6–60.0; NTR] and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. Conclusions There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom. PMID:26750569

  1. NCI Cohort Consortium

    Cancer.gov

    The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

  2. Personal exposure to PM2.5, genetic variants and DNA damage: a multi-center population-based study in Chinese.

    PubMed

    Chu, Minjie; Sun, Chongqi; Chen, Weihong; Jin, Guangfu; Gong, Jianhang; Zhu, Meng; Yuan, Jing; Dai, Juncheng; Wang, Meilin; Pan, Yun; Song, Yuanchao; Ding, Xiaojie; Guo, Xuejiang; Du, Mulong; Xia, Yankai; Kan, Haidong; Zhang, Zhengdong; Hu, Zhibin; Wu, Tangchun; Shen, Hongbing

    2015-06-15

    Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00×10(-3) after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels (P=5.11×10(-3) for POLH, P=2.88×10(-3) for RIT2 and P=2.29×10(-2) for CNTN4). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels. PMID:25889363

  3. International Childhood Cancer Cohort Consortium

    Cancer.gov

    An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

  4. Sample Design and Cohort Selection in the Hispanic Community Health Study/Study of Latinos

    PubMed Central

    LaVange, Lisa M.; Kalsbeek, William; Sorlie, Paul D.; Avilés-Santa, Larissa M.; Kaplan, Robert C.; Barnhart, Janice; Liu, Kiang; Giachello, Aida; Lee, David J.; Ryan, John; Criqui, Michael H.; Elder, John P.

    2010-01-01

    PURPOSE The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a multi-center, community based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this paper. METHODS The study design calls for recruitment and follow-up of a cohort of 16,000 Hispanics/Latinos aged 18-74 years, with 62.5% (10,000) over 44 years of age and adequate subgroup sample sizes to support inference by Hispanic/Latino background. Participants are recruited in community areas surrounding four field centers in the Bronx, Chicago, Miami, and San Diego. A two-stage area probability sample of households is selected with stratification and over-sampling incorporated at each stage to provide a broadly diverse sample, offer efficiencies in field operations, and ensure that the target age distribution is obtained. CONCLUSIONS Embedding probability sampling within this traditional, multi-site cohort study design enables competing research objectives to be met. However, the use of probability sampling requires developing solutions to some unique challenges in both sample selection and recruitment, as described here. PMID:20609344

  5. Cohort Profile: Mysore Parthenon Birth Cohort

    PubMed Central

    Krishnaveni, Ghattu V; Veena, Sargoor R; Hill, Jacqueline C; Karat, Samuel C; Fall, Caroline HD

    2015-01-01

    The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997–98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6–12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up. PMID:24609067

  6. Cohort profile: Mysore parthenon birth cohort.

    PubMed

    Krishnaveni, Ghattu V; Veena, Sargoor R; Hill, Jacqueline C; Karat, Samuel C; Fall, Caroline H D

    2015-02-01

    The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997-98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6-12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up. PMID:24609067

  7. A multi-center randomized proof-of-concept clinical trial applying [¹⁸F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's disease.

    PubMed

    Tzimopoulou, Sofia; Cunningham, Vincent J; Nichols, Thomas E; Searle, Graham; Bird, Nick P; Mistry, Prafull; Dixon, Ian J; Hallett, William A; Whitcher, Brandon; Brown, Andrew P; Zvartau-Hind, Marina; Lotay, Narinder; Lai, Robert Y K; Castiglia, Mary; Jeter, Barbara; Matthews, Julian C; Chen, Kewei; Bandy, Dan; Reiman, Eric M; Gold, Michael; Rabiner, Eugenii A; Matthews, Paul M

    2010-01-01

    Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPARγ agonist Rosiglitazone XR versus placebo in 80 mild to moderate AD patients. Secondary objectives included testing for reduction in the progression of brain atrophy and improvement in cognition. Active treatment was associated with a sustained but not statistically significant trend from the first month for higher mean values in Kiindex and CMRgluindex, novel quantitative indices related to the combined forward rate constant for [18F]FDG uptake and to the rate of cerebral glucose utilization, respectively. However, neither these nor another analytical approach recently validated using data from the Alzheimer's Disease Neuroimaging Initiative indicated that active treatment decreased the progression of decline in brain glucose metabolism. Rates of brain atrophy were similar between active and placebo groups and measures of cognition also did not suggest clear group differences. Our study demonstrates the feasibility of using [18F]FDG-PET as part of a multi-center therapeutics trial. It suggests that Rosiglitazone is associated with an early increase in whole brain glucose metabolism, but not with any biological or clinical evidence for slowing progression over a 1 year follow up in the symptomatic stages of AD. PMID:20930300

  8. Deferiprone versus deferoxamine in sickle cell disease: results from a 5-year long-term Italian multi-center randomized clinical trial.

    PubMed

    Calvaruso, Giusi; Vitrano, Angela; Di Maggio, Rosario; Ballas, Samir; Steinberg, Martin H; Rigano, Paolo; Sacco, Massimiliano; Telfer, Paul; Renda, Disma; Barone, Rita; Maggio, Aurelio

    2014-12-01

    Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although the basal serum ferritin levels were higher in transfused compared with non-transfused group (p=0.031), the changes over time in serum ferritin levels were not statistically significantly different between transfused and non-transfused cohort of patients (p=0.389). Kaplan-Meier curve, during 5-years of study, suggests that Deferiprone does not alter survival in comparison with Deferoxamine (p=0.38). In conclusion, long-term iron chelation therapy with Deferiprone was associated with efficacy and safety similar to that of Deferoxamine. Therefore, in patients with Sickle-Cell-Disease, Deferiprone may represent an effective long-term treatment option. PMID:24814618

  9. A phase I, open-label, multi-center study of the JAK2 inhibitor AZD1480 in patients with myelofibrosis.

    PubMed

    Verstovsek, Srdan; Hoffman, Ronald; Mascarenhas, John; Soria, Jean-Charles; Bahleda, Ratislav; McCoon, Patricia; Tang, Weifeng; Cortes, Jorge; Kantarjian, Hagop; Ribrag, Vincent

    2015-02-01

    The anti-tumor activity of AZD1480, a potent, selective inhibitor of Janus-associated kinases 1 and 2, was demonstrated in preclinical models of myeloproliferative neoplasms. In a phase I clinical study, 35 patients with myelofibrosis received 2.5-70mg AZD1480 orally once daily (QD) or 10 or 15mg twice daily (BID) continuously during repeated 28-day cycles. Two patients experienced dose-limiting toxicities: one patient in the 2.5mg QD cohort had a grade 3 lung infiltration/acute pneumonia, and one patient receiving 50mg QD had grade 3 presyncope. Dosing was stopped at 70mg QD after the first patient experienced an adverse neurological event (AE) and evidence of low-grade neurological toxicity in patients on lower doses after the initial month of therapy became apparent. The most common AZD1480-related AEs were dizziness and anemia. AZD1480 was absorbed quickly and eliminated from the plasma rapidly, with a mean terminal half-life of 2.45-8.06h; accumulation was not observed after repeated daily dosing for 28 days. Four patients showed evidence of clinical improvement based on IWG-MRT 2006 criteria. AZD1480 was relatively well tolerated, however, low-grade, reversible neurological toxicity was therapy limiting and led to study termination. PMID:25530567

  10. Mineral Metabolism in European Children Living with a Renal Transplant: A European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry Study

    PubMed Central

    Bonthuis, Marjolein; Busutti, Marco; Jager, Kitty J.; Baiko, Sergey; Bakkaloğlu, Sevcan; Battelino, Nina; Gaydarova, Maria; Gianoglio, Bruno; Parvex, Paloma; Gomes, Clara; Heaf, James G.; Podracka, Ludmila; Kuzmanovska, Dafina; Molchanova, Maria S.; Pankratenko, Tatiana E.; Papachristou, Fotios; Reusz, György; Sanahuja, Maria José; Shroff, Rukshana; Groothoff, Jaap W.; Schaefer, Franz; Verrina, Enrico

    2015-01-01

    Background and objectives Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. Design, setting, participants, & measurements This study included 1237 children (0–17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. Results Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. Conclusions Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction. PMID:25710805

  11. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. PMID:25964057

  12. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN)

    PubMed Central

    Cairns, Nigel J.; Perrin, Richard J.; Franklin, Erin E.; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J.; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M.; McLean, Catriona; Ghetti, Bernardino; Morris, John C.

    2015-01-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (8), Australia (3), UK (1), and Germany (2). By 2014, 41 ADNI and 24 DIAN autopsies (involving 9 participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform, and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final ‘gold standard’ neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. PMID:25964057

  13. Cohort Size Effects and Migration.

    ERIC Educational Resources Information Center

    Wilson, Franklin D.

    1983-01-01

    Explores whether changes in the size of cohorts entering the labor force affected the propensity within the U.S. labor force to migrate and socioeconomic circumstances of migrants at destination within 1965-76. Suggests that a significant reduction in the volume of migration among members of the baby boom cohort was the primary adjustment…

  14. Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study

    PubMed Central

    Avila-Rios, Santiago; Ormsby, Christopher E; Carlson, Jonathan M; Valenzuela-Ponce, Humberto; Blanco-Heredia, Juan; Garrido-Rodriguez, Daniela; Garcia-Morales, Claudia; Heckerman, David; Brumme, Zabrina L; Mallal, Simon; John, Mina; Espinosa, Enrique; Reyes-Teran, Gustavo

    2009-01-01

    Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC)-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q < 0.2). Strikingly, 23 (53%) of these associations differed from those observed in the well-powered IHAC cohort, strongly suggesting the existence of unique characteristics in HLA-mediated HIV evolution in the Mexican cohort. Furthermore, 17 of the 23 novel associations involved HLA alleles whose frequencies were not significantly different from those in IHAC, suggesting that their detection was not due to increased statistical power but to differences in patterns of epitope targeting. Interestingly, the consensus differed in four positions between the two cohorts and three of these positions could be explained by HLA-associated selection. Additionally, different HLA-HIV codon associations were seen when comparing HLA-mediated selection in plasma viruses and PBMC archived proviruses at the population level, with a significantly lower number of associations in the proviral dataset. Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic

  15. A Cohort, Is a Cohort, Is a Cohort...or Is It?

    ERIC Educational Resources Information Center

    Pemberton, Cynthia Lee A.; Akkary, Rima Karami

    2010-01-01

    This paper presents findings from a multi-year qualitative study based upon life-history narratives of women pursuing doctoral degrees in Educational Leadership. This paper focuses on findings specific to educational cohort models, and suggests that perhaps, at least for women, naturally emergent cohorts--born of relationships of choice--may be…

  16. Cohort: critical science

    NASA Astrophysics Data System (ADS)

    Digney, Bruce L.

    2007-04-01

    Unmanned vehicle systems is an attractive technology for the military, but whose promises have remained largely undelivered. There currently exist fielded remote controlled UGVs and high altitude UAV whose benefits are based on standoff in low complexity environments with sufficiently low control reaction time requirements to allow for teleoperation. While effective within there limited operational niche such systems do not meet with the vision of future military UxV scenarios. Such scenarios envision unmanned vehicles operating effectively in complex environments and situations with high levels of independence and effective coordination with other machines and humans pursing high level, changing and sometimes conflicting goals. While these aims are clearly ambitious they do provide necessary targets and inspiration with hopes of fielding near term useful semi-autonomous unmanned systems. Autonomy involves many fields of research including machine vision, artificial intelligence, control theory, machine learning and distributed systems all of which are intertwined and have goals of creating more versatile broadly applicable algorithms. Cohort is a major Applied Research Program (ARP) led by Defence R&D Canada (DRDC) Suffield and its aim is to develop coordinated teams of unmanned vehicles (UxVs) for urban environments. This paper will discuss the critical science being addressed by DRDC developing semi-autonomous systems.

  17. The WISTAH hand study: A prospective cohort study of distal upper extremity musculoskeletal disorders

    PubMed Central

    2012-01-01

    Background Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors. Methods/design A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain’s stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. Discussion A prospective cohort study of

  18. Study protocol title: a prospective cohort study of low back pain

    PubMed Central

    2013-01-01

    Background Few prospective cohort studies of workplace low back pain (LBP) with quantified job physical exposure have been performed. There are few prospective epidemiological studies for LBP occupational risk factors and reported data generally have few adjustments for many personal and psychosocial factors. Methods/design A multi-center prospective cohort study has been incepted to quantify risk factors for LBP and potentially develop improved methods for designing and analyzing jobs. Due to the subjectivity of LBP, six measures of LBP are captured: 1) any LBP, 2) LBP ≥ 5/10 pain rating, 3) LBP with medication use, 4) LBP with healthcare provider visits, 5) LBP necessitating modified work duties and 6) LBP with lost work time. Workers have thus far been enrolled from 30 different employment settings in 4 diverse US states and performed widely varying work. At baseline, workers undergo laptop-administered questionnaires, structured interviews, and two standardized physical examinations to ascertain demographics, medical history, psychosocial factors, hobbies and physical activities, and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of low back pain. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. The lifetime cumulative incidence of low back pain will also include those with a past history of low back pain. Incident cases will exclude prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. Discussion Data analysis of a prospective cohort study of low back pain is underway and has successfully enrolled over 800 workers to date. PMID:23497211

  19. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    PubMed Central

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  20. The PanAM study: a multi-center, double-blinded, randomized, non-inferiority study of paracetamol versus non-steroidal anti-inflammatory drugs in treating acute musculoskeletal trauma

    PubMed Central

    2013-01-01

    Background Acute musculoskeletal trauma, including strains, sprains or contusions, occur frequently. Pain management is a crucial component of treatment. However, there is no convincing evidence which drug is superior in managing pain in these patients. The aim of the PanAM Study is to compare analgesic efficacy of three strategies of pain management: paracetamol, diclofenac, or a combination of both in patients with acute musculoskeletal trauma. Methods/design The PanAM Study is a multi-center, double blind randomized controlled trial with non-inferiority design. Included are adult patients presenting to an academic, urban Emergency Department or to a General Practice with acute, blunt, traumatic limb injury. In total, 547 patients will be included using a predefined list of exclusion criteria, to be allocated by randomization to treatment with paracetamol + placebo diclofenac, diclofenac + placebo paracetamol or paracetamol + diclofenac. The hypothesis is that paracetamol will not be inferior to treatment with diclofenac, or the combination of both. Primary outcome will be between-group differences in decrease in pain, measured with Numerical Rating Scales at baseline and at 90 minutes after study drug administration. Secondary outcomes are Numerical Rating Scales at 30 and 60 minutes and measured frequently during three consecutive days after discharge; occurrence of adverse effects; patient satisfaction and an analysis of quality of life and cost-effectiveness. Recruitment started July 2013 and is expected to last a year. Discussion With this multi-center randomized clinical trial we will investigate whether treatment with paracetamol alone is not inferior to diclofenac alone or a combination of both drugs in adult patients with acute musculoskeletal trauma. The main relevance of the trial is to demonstrate the benefits and risks of three commonly used treatment regimens for musculoskeletal trauma. Data that lead to the prevention of severe Non

  1. Improving Music Appreciation Class Using Cohort Analysis.

    ERIC Educational Resources Information Center

    Buel, Dona L.; Welch, Samuel C.

    2000-01-01

    Presents a college level music appreciation course that combines cohort analysis, action research methods, and distance learning. Students identify generational cohorts and use research methods to determine the preferred musical forms of the cohort. Describes a "cohort," a music appreciation Web site, the course structure, and benefits of the…

  2. Cohort Profile Update: The 1982 Pelotas (Brazil) Birth Cohort Study

    PubMed Central

    Horta, Bernardo Lessa; Gigante, Denise P; Gonçalves, Helen; dos Santos Motta, JanainaVieira; Loret de Mola, Christian; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G

    2015-01-01

    In this manuscript, we update the profile of the 1982 Pelotas Birth Cohort Study.In 1982, 5914 live births whose families lived in the urban are of Pelotas were enrolled in the cohort. In 2012–13, we tried to locate the whole original cohort; 3701 participants were interviewed who, added to the 325 known deaths, represented a follow-up rate of 68.1%. In contrast to the previous home interviews, in this wave all participants were invited to visit the research clinic to be interviewed and examined. The visit was carried out at a mean age of 30.2 years and mainly focused on four categories of outcomes: (i) mental health; (ii) body composition; (iii) precursors of complex chronic diseases; and (iv) human capital. Requests for collaboration by outside researchers are welcome. PMID:25733577

  3. Statistical analysis plan for the Stroke Oxygen Study (SO2S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome

    PubMed Central

    2014-01-01

    Background The Stroke Oxygen Study (SO2S) is a multi-center randomized controlled trial of oxygen supplementation in patients with acute stroke. The main hypothesis for the trial is that fixed-dose oxygen treatment during the first 3 days after an acute stroke improves outcome. The secondary hypothesis is that restricting oxygen supplementation to night time only is more effective than continuous supplementation. This paper describes the statistical analysis plan for the study. Methods and design Patients (n = 8000) are randomized to three groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen supplementation for three nights; and (3) no routine oxygen supplementation. Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary outcome measure is the modified Rankin scale at 90 days. Data will be analyzed according to the intention-to-treat principle. Methods of statistical analysis are described, including the handling of missing data, the covariates used in adjusted analyses, planned subgroups analyses, and planned sensitivity analyses. Trial registration This trial is registered with the ISRCTN register, number ISRCTN52416964 (30 September 2005). PMID:24939648

  4. Prospective multi-center study for quantification of chemotherapies and CTX-related direct medication costs avoided by use of biomarkers uPA and PAI-1 in primary breast cancer.

    PubMed

    Jacobs, Volker R; Augustin, Doris; Wischnik, Arthur; Kiechle, Marion; Höss, Cornelia; Steinkohl, Oliver; Rack, Brigitte; Kapitza, Thomas; Krase, Peter

    2013-08-01

    Biomarkers uPA/PAI-1 as recommended by ASCO and AGO are used in primary breast cancer to avoid unnecessary CTX in medium risk-recurrence patients. This study verified how many CTX cycles and CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. A prospective, non-interventional, multi-center study was performed among six Certified Breast Centers to analyze application of uPA/PAI-1 and consecutive decision-making. CTX avoided were identified and direct costs for CTX, CTX-related concomitant medication and febrile neutropenia (FN) prophylaxis with G-CSF calculated. In n = 93 breast cancers n = 35 CTX (37.6%) with 210 CTX cycles were avoided according to uPA/PAI-1 test result. uPA/PAI-1 testing saved direct medication costs for CTX of 177,453 €, CTX-related concomitant medication of 27,482 € and FN prophylaxis of 20,599 €, overall 225,534 €. At test costs at 287.50 € uPA/PAI-1 testing resulted in additional costs of 26,737.50 €. uPA/PAI-1 has proven to be cost-effective at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. These results support decision-making for cost-effective diagnostics and therapy in breast cancer. PMID:23643802

  5. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein–Zernike self-consistent field approach

    SciTech Connect

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-07

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein–Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple S{sub N}2 reaction (Cl{sup −} + CH{sub 3}Cl → ClCH{sub 3} + Cl{sup −}) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  6. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein-Zernike self-consistent field approach

    NASA Astrophysics Data System (ADS)

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl- + CH3Cl → ClCH3 + Cl-) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  7. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

    PubMed

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF. PMID:26156461

  8. A Phase III, Randomized, Multi-Center, Double-Masked, Matched-Pairs, Active-Controlled Trial to Compare the Efficacy and Safety between Neuramis Deep and Restylane in the Correction of Nasolabial Folds

    PubMed Central

    Pak, Changsik; Park, Jihoon; Hong, Jinmyung; Jeong, Jaehoon; Bang, Saik

    2015-01-01

    Background We conducted this clinical study to compare the efficacy and safety between Neuramis Deep and Restylane in the correction of nasolabial folds. Methods In this phase III, randomized, multi-center, double-masked, matched-pairs, active-controlled trial (ClinicalTrials.gov Identifier: NCT01585220), we evaluated a total of 67 subjects (n=67). All the subjects underwent Neuramis Deep treatment on one side and Restylane on the contralateral side of the bilateral nasolabial folds at a ratio of 1:1. To compare the efficacy of Neuramis Deep and Restylane, we evaluated the Wrinkle Severity Rating Scale scores and those of the Global Aesthetic Improvement Scale. In addition, we compared the safety of Neuramis Deep and Restylane based on adverse events, physical examination, and clinical laboratory tests. Results Neuramis Deep was not inferior in improving the nasolabial folds as compared with Restylane. In addition, there was no significant difference in the efficacy between Neuramis Deep and Restylane. There were no significant differences in safety parameters between Neuramis Deep and Restylane. Conclusions In conclusion, our results indicate that Neuramis Deep may be a safe, effective material for improving the nasolabial folds. However, further studies are warranted to compare the tolerability of Neuramis Deep and Restylane based on histopathologic findings. PMID:26618119

  9. Evaluations of treatment efficacy of depression from perspective of both patients' symptoms and general sense of mental health and wellbeing: A large scale, multi-centered, longitudinal study in China.

    PubMed

    Zeng, Qingzhi; Wang, Wei Chun; Fang, Yiru; Mellor, David; Mccabe, Marita; Byrne, Linda; Zuo, Sai; Xu, Yifeng

    2016-07-30

    Relying on the absence, presence of level of symptomatology may not provide an adequate indication of the effects of treatment for depression, nor sufficient information for the development of treatment plans that meet patients' needs. Using a prospective, multi-centered, and observational design, the present study surveyed a large sample of outpatients with depression in China (n=9855). The 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Remission Evaluation and Mood Inventory Tool (REMIT) were administered at baseline, two weeks later and 4 weeks, to assess patients' self-reported symptoms and general sense of mental health and wellbeing. Of 9855 outpatients, 91.3% were diagnosed as experiencing moderate to severe depression. The patients reported significant improvement over time on both depressive symptoms and general sense after 4-week treatment. The effect sizes of change in general sense were lower than those in symptoms at both two week and four week follow-up. Treatment effects on both general sense and depressive symptomatology were associated with demographic and clinical factors. The findings indicate that a focus on both general sense of mental health and wellbeing in addition to depressive symptomatology will provide clinicians, researchers and patients themselves with a broader perspective of the status of patients. PMID:27156024

  10. [Biobanks European infrastructure].

    PubMed

    Kinkorová, Judita; Topolčan, Ondřej

    2016-01-01

    Biobanks are structured repositories of human tissue samples connected with specific information. They became an integral part of personalized medicine in the new millennium. At the European research area biobanks are isolated not well coordinated and connected to the network. European commission supports European infrastructure BBMRI-ERIC (Biobanks and Biomolecular Resources Research Infrastructure European Research Infrastructure Consortium), consortium of 54 members with more than 225 associated organizations, largely biobanks from over 30 countries. The aim is to support biomedical research using stored samples. Czech Republic is a member of the consortium as a national node BBMRI_CZ, consisting of five partners. PMID:27256149

  11. The Lisbon Cohort of men who have sex with men

    PubMed Central

    Meireles, Paula; Lucas, Raquel; Martins, Ana; Carvalho, Ana Cláudia; Fuertes, Ricardo; Brito, João; Campos, Maria José; Mendão, Luís; Barros, Henrique

    2015-01-01

    Purpose Newly diagnosed HIV infections among men who have sex with men (MSM) are rising in many European countries. Surveillance tools must be tailored to the current state of the epidemic, and include decentralised prospective monitoring of HIV incidence and behavioural changes in key populations. In this scenario, an open prospective cohort study was assembled—The Lisbon Cohort of MSM—aiming to dynamically monitor the frequency of disease and its predictors. Participants The Lisbon Cohort of MSM is an ongoing observational prospective study conducted at a community-based voluntary HIV counselling and testing centre in Lisbon, Portugal (CheckpointLX). Men testing negative for HIV, aged 18 or over and reporting having had sex with men are invited to follow-up visits every 6 months. At each evaluation, a face-to-face interview using a structured questionnaire is conducted, and HIV and syphilis rapid tests are performed by trained peer counsellors. From April 2011 to February 2014, 3106 MSM were eligible to the cohort of whom 923 (29.7%) did not participate. The remaining 2183 (70.3%) MSM were enrolled and 804 had at least one follow-up evaluation, for a total of 893 person-years of observation. Future plans The study findings will be disseminated in peer-reviewed journals and presented at national and international conferences. The follow-up of this cohort of HIV-negative MSM will be a valuable tool for monitoring HIV incidence in a setting where limited prospective information existed. Moreover, it will allow for a deeper analytical approach to the study of population time trends and individual changes in risk factors that currently shape the HIV epidemic among MSM. PMID:25967995

  12. European auxiliary propulsion, 1972

    NASA Technical Reports Server (NTRS)

    Holcomb, L. B.

    1972-01-01

    The chemical and electric auxiliary propulsion technology of the United Kingdom, France, and West Germany is discussed in detail, and the propulsion technology achievements of Italy, India, Japan, and Russia are reviewed. A comparison is presented of Shell 405 catalyst and a European spontaneous hydrazine catalyst called CNESRO I. Finally, conclusions are drawn regarding future trends in European auxiliary propulsion technology development.

  13. Methodology Series Module 1: Cohort Studies

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies. PMID:26955090

  14. Cohort Default Rates in Context

    ERIC Educational Resources Information Center

    Looney, Shannon M.

    2011-01-01

    Burgeoning student loan debt indicates problems not only for the country's borrowers but also for the postsecondary system. The rise in student loan defaults signifies a rise in institutional cohort default rates (CDRs)--a measure of accountability that informs the government and the general public how well an institution prepares its students for…

  15. Fit to WHO weight standard of European infants over time

    PubMed Central

    Levin, Daniel; Marryat, Louise; Cole, Tim J; McColl, John; Harjunmaa, Ulla; Ashorn, Per; Wright, Charlotte

    2016-01-01

    Objectives The 2006 WHO growth charts were created to provide an international standard for optimal growth, based on healthy, breastfed populations, but it has been suggested that Northern European children fit them poorly. This study uses infant weight data spanning 50 years to determine how well-nourished preschool children from different eras fit the WHO standard, and discuss the implications of deviations. Design Four longitudinal datasets from the UK and one from Finland were used comprising over 8000 children born between1959 and 2003. Weights from birth to 2 years were converted to age–sex-adjusted Z scores using the WHO standard and summarised using Generalized Additive Models for Location, Scale and Shape. Results Weights showed a variable fit to the WHO standard. Mean weights for all cohorts were above the WHO median at birth, but dipped by up to 0.5 SD to a nadir at 8 weeks before rising again. Birth weights increased in successive cohorts and the initial dip became slightly shallower. By age 1 year, cohorts were up to 0.75 SD above the WHO median, but there was no consistent pattern by era. Conclusions The WHO standard shows an acceptable, but variable fit for Northern European infants. While birth weights increased over time, there was, unexpectedly, no consistent variation by cohort beyond this initial period. Discrepancies in weight from the standard may reflect differences in measurement protocol and trends in infant feeding practice. PMID:26883079

  16. Clinical utility of simultaneous measurement of alpha-fetoprotein and des-γ-carboxy prothrombin for diagnosis of patients with hepatocellular carcinoma in China: A multi-center case-controlled study of 1,153 subjects.

    PubMed

    Song, Peipei; Feng, Xiaobin; Inagaki, Yoshinori; Song, Tianqiang; Zhang, Keming; Wang, Zhigang; Zheng, Shuguo; Ma, Kuansheng; Li, Qiang; Kong, Dalu; Wu, Qiang; Zhang, Ti; Zhao, Xin; Hasegawa, Kiyoshi; Sugawara, Yasuhiko; Kokudo, Norihiro; Tang, Wei

    2014-10-01

    This study aimed to investigate the clinical utility of simultaneous measurement of alphafetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma (HCC) diagnosis in Chinese patients predominantly caused by hepatitis B virus infection by a multi-center case-controlled study. Subjects were 1,153 individuals from three major hospitals in China, including 550 cases in HCC group, 164 in Malignant disease group, 182 in Benign disease group, 85 in Chronic liver disease group, and 173 in Normal group. Serum levels of AFP and DCP were measured and clinicopathological features were determined for all subjects. Results showed that the levels of DCP and AFP were significantly higher in HCC group (550 patients, 74.18% with HBV infection) than that in other four groups (P < 0.001). Receiver operating curves (ROC) indicated the optimal cut-off value was 86 mAU/mL for DCP with a sensitivity of 71.50% and specificity of 86.30%, and 21 ng/mL for AFP with a sensitivity of 68.00% and specificity of 93.20%. The area under ROC curve was 0.846 for DCP, 0.832 for AFP, and 0.890 for the combination of DCP and AFP. The combination of DCP and AFP resulted in a higher Youden index and a sensitivity of approximately 90%, even for small tumors. The simultaneous measurement of AFP and DCP could achieve a better sensitivity in diagnosing Chinese HCC patients, even for small tumors. PMID:25382443

  17. Real-world Experience of Carotid Artery Stenting in Japan: Analysis of 7,134 Cases from JR-NET1 and 2 Nationwide Retrospective Multi-center Registries

    PubMed Central

    EGASHIRA, Yusuke; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; ENOMOTO, Yukiko

    2014-01-01

    The present study aimed to demonstrate the “real-world” experiences of carotid artery stenting (CAS) in Japan using Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2, retrospective nationwide multi-center surveillances. JR-NET1 and 2 registries are retrospective surveillances conducted between January 2005 and December 2007 and January 2008 and December 2009, respectively, in Japan regarding neuroendovascular therapy. A total of 7,134 procedures (1,943 for JR-NET1 and 5,191 for JR-NET2) were included in this study and retrieved data were analyzed retrospectively. Treatment results of two surveillance periods were similar. In JR-NET2 registry, total of 5,191 lesions were treated by CAS and 5,008 of 5,191 procedures (96.5%) were performed by the board-certified surgeons of Japanese Society of Neuroendovascular Therapy. The rate of technical success was extremely high (99.99%), and the rate of clinically significant complication was low (3.2%). These results were comparable to a previous large study in Japan. Multivariate logistic analysis revealed that age [odds ratio (OR), 1.04 per year; 95% confidence interval (CI), 1.02–1.07; p = 0.0004), symptomatic lesion (OR, 1.87; 95% CI; p = 0.0004), and the use of closed-cell type stent (OR, 0.58; 95% CT, 0.32–1.00; p = 0.05) were independently associated with clinically significant complications. It was revealed that good clinical results were achieved in patients who underwent CAS in Japan. It is expected that the evolution of devices and increasing experiences of surgeons would lead to further improvement of the clinical results, and further investigation would be required to clarify the optimal treatment strategy and therapeutic efficacy of CAS, especially in symptomatic lesions. PMID:24305031

  18. A Randomized, Double-blind, Placebo-controlled, Multi-center, Extension Trial Evaluating the Efficacy of a New Oral Supplement in Women with Self-perceived Thinning Hair

    PubMed Central

    Dayan, Steven

    2015-01-01

    Objective: The purpose of this six-month, randomized, double-blind, multi-center, placebo-controlled study was to determine if the administration of a new oral supplement will promote terminal hair growth. Design: A randomized, double-blind study. Setting: Two private practices (dermatology and facial plastics). Participants: Women 21 to 75 years of age with self-perceived thinning hair. Measurements: The primary efficacy endpoint was the change in terminal and vellus hairs in a 4cm2 target area of the scalp after 90 and 180 days of treatment. Secondary endpoints were change in hair diameter and responses to Quality of Life and Self-Assessment questionnaires. Results: Subjects treated with the new oral supplement achieved a significant increase in the number of baseline terminal hairs at 90 and 180 days (for each, p<0.0001, respectively) and were significantly greater then placebo (p<0.0001). Treatment with the new oral supplement was also associated with a significant increase in baseline terminal hair diameter after 90 (p=0.006) and 180 days of treatment (p=0.001) which was significantly greater than placebo at the end of the study (p=0.003). Improvements in hair growth and hair diameter were associated with significant improvement in most responses to Self-Assessment and Quality of Life Questionnaire responses. There were no adverse events. Conclusion: The daily administration of a new oral supplement was associated with significant increases in the number of terminal and vellus hairs and hair diameter. Most study participants believed the use of the oral supplement resulted in significant improvement in skin and hair quality and quality of life. PMID:26705444

  19. A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

    PubMed Central

    Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

    2010-01-01

    Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

  20. HHV8 and Kaposi's sarcoma: a time cohort study.

    PubMed Central

    Kennedy, M M; Lucas, S B; Jones, R R; Howells, D D; Picton, S J; Hanks, E E; McGee, J O; O'Leary, J J

    1997-01-01

    AIMS: The recent finding that human herpes virus 8 (HHV8) is found in the majority of Kaposi's sarcoma (KS) cases supports the epidemiological observation that the tumour may be caused by an infectious agent. This study aimed to address when and how HHV8 evolved. METHODS: A cohort of African endemic KS (49 samples from 45 patients) and European KS (18 samples from 13 patients), spanning 27 years, was assessed for the presence of HHV8 by both standard solution phase polymerase chain reaction (PCR) and the newly described technique of TaqMan PCR. RESULTS: HHV8 was present in approximately 49% (24 of 49 tissue samples) of the African cases and in more than 90% (16 of 18 tissue samples) of the European cohort, in keeping with recent seroepidemiological data. CONCLUSIONS: HHV8 is strongly linked to the development of KS; however, in some patients, other factors may operate. The utility and flexibility of TaqMan PCR in detecting low copy viral target in human tissues was demonstrated. Images PMID:9231158

  1. EpiDEA: Extracting Structured Epilepsy and Seizure Information from Patient Discharge Summaries for Cohort Identification

    PubMed Central

    Cui, Licong; Bozorgi, Alireza; Lhatoo, Samden D.; Zhang, Guo-Qiang; Sahoo, Satya S.

    2012-01-01

    Sudden Unexpected Death in Epilepsy (SUDEP) is a poorly understood phenomenon. Patient cohorts to power statistical studies in SUDEP need to be drawn from multiple centers due to the low rate of reported SUDEP incidences. But the current practice of manual chart review of Epilepsy Monitoring Units (EMU) patient discharge summaries is time-consuming, tedious, and not scalable for large studies. To address this challenge in the multi-center NIH-funded Prevention and Risk Identification of SUDEP Mortality (PRISM) Project, we have developed the Epilepsy Data Extraction and Annotation (EpiDEA) system for effective processing of discharge summaries. EpiDEA uses a novel Epilepsy and Seizure Ontology (EpSO), which has been developed based on the International League Against Epilepsy (ILAE) classification system, as the core knowledge resource. By extending the cTAKES natural language processing tool developed at the Mayo Clinic, EpiDEA implements specialized functions to address the unique challenges of processing epilepsy and seizure-related clinical free text in discharge summaries. The EpiDEA system was evaluated on a corpus of 104 discharge summaries from the University Hospitals Case Medical Center EMU and achieved an overall precision of 93.59% and recall of 84.01% with an F-measure of 88.53%. The results were compared against a gold standard created by two epileptologists. We demonstrate the use of EpiDEA for cohort identification through use of an intuitive visual query interface that can be directly used by clinical researchers. PMID:23304396

  2. A Study of Group Dynamics in Educational Leadership Cohort and Non-Cohort Groups

    ERIC Educational Resources Information Center

    Greenlee, Bobbie J.; Karanxha, Zorka

    2010-01-01

    The purpose of this study was to examine group dynamics of educational leadership students in cohorts and make comparisons with the group dynamics characteristics of non-cohort students. Cohorts have emerged as dynamic and adaptive entities with attendant group dynamic processes that shape collective learning and action. Cohort (n=42) and…

  3. The European Spallation Source

    NASA Astrophysics Data System (ADS)

    Lindroos, M.; Bousson, S.; Calaga, R.; Danared, H.; Devanz, G.; Duperrier, R.; Eguia, J.; Eshraqi, M.; Gammino, S.; Hahn, H.; Jansson, A.; Oyon, C.; Pape-Møller, S.; Peggs, S.; Ponton, A.; Rathsman, K.; Ruber, R.; Satogata, T.; Trahern, G.

    2011-12-01

    In 2003 the joint European effort to design a European Spallation Source (ESS) resulted in a set of reports, and in May 2009 Lund was agreed to be the ESS site. The ESS Scandinavia office has since then worked on setting all the necessary legal and organizational matters in place so that the Design Update and construction can be started in January 2011, in collaboration with European partners. The Design Update phase is expected to end in 2012, to be followed by a construction phase, with first neutrons expected in 2018-2019.

  4. European PTTI report

    NASA Technical Reports Server (NTRS)

    Cordara, Franco; Grimaldi, Sabrina; Leschiutta, Sigfrido

    1994-01-01

    Time and frequency metrology in Europe presents some peculiar features in its three main components: research on clocks, comparisons and dissemination methods, and dissemination services. Apart from the usual activities of the national metrological laboratories, an increasing number of cooperation between the European countries are promoted inside some European organizations, such as the ECC, EFTA, EUROMET, and WECC. Cooperation between these organizations is covered. The present, evolving situation will be further influenced by the recent political changes in Eastern Europe.

  5. Birth cohorts in asthma and allergic diseases: report of a NIAID/NHLBI/MeDALL joint workshop.

    PubMed

    Bousquet, Jean; Gern, James E; Martinez, Fernando D; Anto, Josep M; Johnson, Christine C; Holt, Patrick G; Lemanske, Robert F; Le Souëf, Peter N; Tepper, Robert S; von Mutius, Erika R M; Arshad, S Hasan; Bacharier, Leonard B; Becker, Allan; Belanger, Kathleen; Bergström, Anna; Bernstein, David I; Cabana, Michael D; Carroll, Kecia N; Castro, Mario; Cooper, Philip J; Gillman, Matthew W; Gold, Diane R; Henderson, John; Heinrich, Joachim; Hong, Soo-Jong; Jackson, Daniel J; Keil, Thomas; Kozyrskyj, Anita L; Lødrup Carlsen, Karin C; Miller, Rachel L; Momas, Isabelle; Morgan, Wayne J; Noel, Patricia; Ownby, Dennis R; Pinart, Mariona; Ryan, Patrick H; Schwaninger, Julie M; Sears, Malcolm R; Simpson, Angela; Smit, Henriette A; Stern, Debra A; Subbarao, Padmaja; Valenta, Rudolf; Wang, Xiaobin; Weiss, Scott T; Wood, Robert; Wright, Anne L; Wright, Rosalind J; Togias, Alkis; Gergen, Peter J

    2014-06-01

    Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. PMID:24636091

  6. The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol

    PubMed Central

    2014-01-01

    Background Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion. Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. Methods/Design This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18–75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. Discussion In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled

  7. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial

    PubMed Central

    2011-01-01

    Background Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation. Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. Methods/Design ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool. The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central

  8. Safety and effectiveness of minimally invasive sacroiliac joint fusion in women with persistent post-partum posterior pelvic girdle pain: 12-month outcomes from a prospective, multi-center trial.

    PubMed

    Capobianco, Robyn; Cher, Daniel

    2015-01-01

    Postpartum posterior pelvic girdle pain (PPGP) affects nearly 20 % of women who experience back pain in the peripartum period. The sacroiliac joint is a source of this pain in 75 % of women with persistent PPGP. A subset of women will fail to obtain acceptable pain relief from the current array of non-surgical treatment options. The purpose of this study is to assess the safety and effectiveness of minimally invasive sacroiliac (SI) joint fusion in women with chronic SI joint dysfunction whose pain began in the peri-partum period whose symptoms were recalcitrant to non-surgical management. A sub-group analysis of subjects with sacroiliac joint disruption and/or degenerative sacroiliitis enrolled in a prospective, multi-center trial of SI joint fusion was performed. Subjects with PPGP were identified and compared with women without PPGP and with men. Of 172 enrolled subjects, 52 were male, 100 were females without PPGP and 20 females had PPGP. PPGP subjects were significantly younger (43.3 years, vs. 52.8 for females without PPGP and 50.5 for men, p = 0.002). There were no differences in any other demographic or baseline clinical measure. Women with PPGP experienced a significant improvement in pain (-51 mm on VAS), function (-20.6 pts on ODI) and quality of life (SF-36 PCS +10.4, MCS +7.2, EQ-5D +0.31) at 12 months after surgery. These improvements were characteristic of the overall study results; no difference was detected between sub-groups. The sacroiliac joint can be a source of pain in women with persistent PPGP and should be investigated as a pain generator. In this study, women with carefully diagnosed chronic SI joint pain from PPGP recalcitrant to conservative therapies experienced clinically beneficially improvements in pain, disability and quality of life after minimally invasive SI joint fusion using a series of triangular porous plasma spray coated implants. PMID:26543705

  9. Riyadh Mother and Baby Multicenter Cohort Study: The Cohort Profile

    PubMed Central

    Esmaeil, Samia; Alzeidan, Rasmieh; Elawad, Mamoun; Tabassum, Rabeena; Hansoti, Shehnaz; Magzoup, Mohie Edein; Al-Kadri, Hanan; Elsherif, Elham; Al-Mandil, Hazim; Al-Shaikh, Ghadeer; Zakaria, Nasria

    2016-01-01

    Objectives To assess the effects of non-communicable diseases, such as diabetes, hypertension and obesity, on the mother and the infant. Methods A multicentre cohort study was conducted in three hospitals in the city of Riyadh in Saudi Arabia. All Saudi women and their babies who delivered in participating hospitals were eligible for recruitment. Data on socio-demographic characteristics in addition to the maternal and neonatal outcomes of pregnancy were collected. The cohort demographic profile was recorded and the prevalence of maternal conditions including gestational diabetes, pre-gestational diabetes, hypertensive disorders in pregnancy and obesity were estimated. Findings The total number of women who delivered in participating hospitals during the study period was 16,012 of which 14,568 women participated in the study. The mean age of the participants was 29 ± 5.9 years and over 40% were university graduates. Most of the participants were housewives, 70% were high or middle income and 22% were exposed to secondhand smoke. Of the total cohort, 24% were married to a first cousin. More than 68% of the participants were either overweight or obese. The preterm delivery rate was 9%, while 1.5% of the deliveries were postdate. The stillbirth rate was 13/1000 live birth. The prevalence of gestational diabetes was 24% and that of pre-gestational diabetes was 4.3%. The preeclampsia prevalence was 1.1%. The labour induction rate was 15.5% and the cesarean section rate was 25%. Conclusion Pregnant women in Saudi Arabia have a unique demographic profile. The prevalence of obesity and diabetes in pregnancy are among the highest in the world. PMID:26937965

  10. Issues of methods and interpretation in the National Cancer Institute formaldehyde cohort study

    PubMed Central

    2014-01-01

    In 2004, the International Agency for Research on Cancer (IARC) reclassified formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group 1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up through 1994 of the National Cancer Institute formaldehyde cohort study. To the contrary, in 2012, the Committee for Risk Assessment of the European Chemicals Agency disagreed with the proposal to classify FA as a known human carcinogen (Carc. 1A), proposing a lower but still protective category, namely as a substance which is presumed to have carcinogenic potential for humans (Carc. 1B). Thus, U.S. and European regulatory agencies currently disagree about the potential human carcinogenicity of FA. In 2013, the National Cancer Institute reported results from their follow-up through 2004 of the formaldehyde cohort and concluded that the results continue to suggest a link between FA exposure and NPC. We discuss in this commentary why we believe that this interpretation is neither consistent with the available data from the most recent update of the National Cancer Institute cohort study nor with other research findings from that cohort, other large cohort studies and the series of publications by some of the current authors, including an independent study of one of the National Cancer Institute’s study plants. Another serious concern relates to the incorrectness of the data from the follow-up through 1994 of the National Cancer Institute study stemming from incomplete mortality ascertainment. While these data were corrected by the National Cancer Institute in subsequent supplemental publications, incorrect data from the original publications have been cited extensively in recent causal evaluations of FA, including IARC. We conclude that the NCI publications that contain incorrect data from the incomplete 1994 mortality follow-up should be retracted entirely or corrected via published errata in the corresponding journals, and efforts