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1

HPV-associated lung cancers: an international pooled analysis.  

PubMed

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship. PMID:24523449

Ragin, Camille; Obikoya-Malomo, Monisola; Kim, Sungjin; Chen, Zhengjia; Flores-Obando, Rafael; Gibbs, Denise; Koriyama, Chihaya; Aguayo, Francisco; Koshiol, Jill; Caporaso, Neil E; Carpagnano, Giovanna E; Ciotti, Marco; Dosaka-Akita, Hirotoshi; Fukayama, Masashi; Goto, Akiteru; Spandidos, Demetrios A; Gorgoulis, Vassilis; Heideman, Daniëlle A M; van Boerdonk, Robert A A; Hiroshima, Kenzo; Iwakawa, Reika; Kastrinakis, Nikolaos G; Kinoshita, Ichiro; Akiba, Suminori; Landi, Maria T; Eugene Liu, H; Wang, Jinn-Li; Mehra, Ranee; Khuri, Fadlo R; Lim, Wan-Teck; Owonikoko, Taofeek K; Ramalingam, Suresh; Sarchianaki, Emmanuela; Syrjanen, Kari; Tsao, Ming-Sound; Sykes, Jenna; Hee, Siew Wan; Yokota, Jun; Zaravinos, Apostolos; Taioli, Emanuela

2014-06-01

2

Parental age and risk of childhood cancer: A pooled analysis  

PubMed Central

Background Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. Methods We assessed the relationship between parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0–14 years during 1980–2004 and 57,966 controls born during 1970–2004. Persons with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. Results Positive linear trends per 5-year maternal age increase were –observed for childhood cancers overall (odds ratio = 1.08 [95% confidence interval = 1.06–1.10]) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 [1.05–1.11]), lymphoma (1.06 [1.01–1.12]), central nervous system tumors (1.07 [1.03–1.10]), neuroblastoma (1.09 [1.04–1.15]), Wilms’ tumor (1.16 [1.09–1.22]), bone tumors (1.10 [ 1.00–1.20]), and soft tissue sarcomas (1.10 [1.04–1.17]). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. Conclusions Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.

Johnson, Kimberly J.; Carozza, Susan E.; Chow, Eric J.; Fox, Erin E.; Horel, Scott; McLaughlin, Colleen C.; Mueller, Beth A.; Puumala, Susan E.; Reynolds, Peggy; Behren, Julie Von; Spector, Logan G.

2009-01-01

3

Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium.  

PubMed

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984-2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk. PMID:22986146

Brenner, Darren R; Boffetta, Paolo; Duell, Eric J; Bickeböller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E; Yang, Ping; Wichmann, H-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G; Cote, Michele L; Tjønneland, Anne; Friis, Søren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N; Lazarus, Philip; Field, John K; Raji, Olaide; McLaughlin, John R; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J; Hung, Rayjean J

2012-10-01

4

Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the International Lung Cancer Consortium  

PubMed Central

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.

Brenner, Darren R.; Boffetta, Paolo; Duell, Eric J.; Bickeboller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E.; Yang, Ping; Wichmann, H.-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G.; Cote, Michele L.; Tj?nneland, Anne; Friis, S?ren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N.; Lazarus, Philip; Field, John K.; Raji, Olaide; McLaughlin, John R.; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S.; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J.; Hung, Rayjean J.

2012-01-01

5

A pooled analysis of case-control studies of thyroid cancer ¶II. Menstrual and reproductive factors  

Microsoft Academic Search

Objective: It has been suggested that female hormones, and hence menstrual and reproductive factors, play a role in thyroid cancer etiology. Epidemiological data, however, are limited and inconsistent, partly because of the small number of cases included in each study. To clarify the etiology of thyroid cancer, we conducted a pooled analysis of original data from 14 case-control studies, 4

Eva Negri; Luigino Dal Maso; Elaine Ron; Carlo La Vecchia; Steven D. Mark; Susan Preston-Martin; Anne McTiernan; Laurence Kolonel; Yasuhiko Yoshimoto; Fan Jin; Gun Wingren; Maria Rosaria Galanti; Lennart Hardell; Eystein Glattre; Eiliv Lund; Fabio Levi; Dimitrios Linos; Claudia Braga; Silvia Franceschi

1999-01-01

6

Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies  

PubMed Central

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case–control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529?638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86–1.44 comparing ?30 to 0?g?day?1 of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.

Genkinger, J M; Hunter, D J; Spiegelman, D; Anderson, K E; Buring, J E; Freudenheim, J L; Goldbohm, R A; Harnack, L; Hankinson, S E; Larsson, S C; Leitzmann, M; McCullough, M L; Marshall, J; Miller, A B; Rodriguez, C; Rohan, T E; Schatzkin, A; Schouten, L J; Wolk, A; Zhang, S M; Smith-Warner, S A

2006-01-01

7

International Pooled Analysis of Risk Factors for Thyroid Cancer  

Cancer.gov

For reasons that are not currently well understood, the incidence of thyroid cancer has rapidly increased in several countries over the past three decades.  Individual case-control and cohort studies have suggested links between taller height and greater

8

Vitamin D and prevention of breast cancer: Pooled analysis  

Microsoft Academic Search

BackgroundInadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose–response relationship in individuals has not been adequately studied.

Cedric F. Garland; Edward D. Gorham; Sharif B. Mohr; William B. Grant; Edward L. Giovannucci; Martin Lipkin; Harold Newmark; Michael F. Holick; Frank C. Garland

2007-01-01

9

Vitamin D and prevention of breast cancer: Pooled analysis  

Microsoft Academic Search

Background: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose-response relationship in individuals has not been adequately studied. 17 18 Methods: A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with

Cedric F. Garland; Edward D. Gorham; Sharif B. Mohr; William B. Grant; Edward L. Giovannucci; Martin Lipkin; Harold Newmark; Michael F. Holick; Frank C. Garland

2006-01-01

10

Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium  

PubMed Central

Purpose Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). Methods The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case–control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Results Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2–8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). Conclusions These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

Steplowski, Emily; Yu, Kai; Hartge, Patricia; Tobias, Geoffrey S.; Brotzman, Michelle J.; Chanock, Stephen J.; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Helzlsouer, Kathy; Jacobs, Eric J.; LaCroix, Andrea; Petersen, Gloria; Zheng, Wei; Albanes, Demetrius; Allen, Naomi E.; Amundadottir, Laufey; Bao, Ying; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Gaziano, J. Michael; Giovannucci, Edward L.; Duell, Eric J.; Hallmans, Goran; Howard, Barbara V.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kooperberg, Charles; Kraft, Peter; Mendelsohn, Julie B.; Michaud, Dominique S.; Palli, Domenico; Phillips, Lawrence S.; Overvad, Kim; Patel, Alpa V.; Sansbury, Leah; Shu, Xiao-Ou; Simon, Michael S.; Slimani, Nadia; Trichopoulos, Dimitrios; Visvanathan, Kala; Virtamo, Jarmo; Wolpin, Brian M.; Zeleniuch-Jacquotte, Anne; Fuchs, Charles S.; Hoover, Robert N.; Gross, Myron

2012-01-01

11

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.  

PubMed

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ?500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ?1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk. PMID:24631943

Genkinger, J M; Wang, M; Li, R; Albanes, D; Anderson, K E; Bernstein, L; van den Brandt, P A; English, D R; Freudenheim, J L; Fuchs, C S; Gapstur, S M; Giles, G G; Goldbohm, R A; Håkansson, N; Horn-Ross, P L; Koushik, A; Marshall, J R; McCullough, M L; Miller, A B; Robien, K; Rohan, T E; Schairer, C; Silverman, D T; Stolzenberg-Solomon, R Z; Virtamo, J; Willett, W C; Wolk, A; Ziegler, R G; Smith-Warner, S A

2014-06-01

12

Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies  

PubMed Central

Purpose The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. Methods We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Results Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose– response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Conclusions Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

Faber, Mette T.; Kjaer, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K.; H?gdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Doherty, Jennifer A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Ness, Roberta B.; Modugnos, Francesmary; Edwards, Robert P.; Bunker, Clareann H.; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Larson, Melissa C.; Schildkraut, Joellen; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Bandera, Elisa V.; Olson, Sara H.; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H.; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P.; Moysich, Kirsten B.; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H.; Pike, Malcolm C.; Risch, Harvey A.

2013-01-01

13

Sinonasal cancer and occupational exposures: a pooled analysis of 12 case–control studies  

Microsoft Academic Search

Objective: In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case–control studies conducted in seven countries were pooled and reanalyzed. Methods: The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls

Danièle Luce; Annette Leclerc; Denis Bégin; Paul A. Demers; Michel Gérin; Ewa Orlowski; Manolis Kogevinas; Stefano Belli; Isabelle Bugel; Ulrich Bolm-Audorff; Louise A. Brinton; Pietro Comba; Lennart Hardell; Richard B. Hayes; Corrado Magnani; Enzo Merler; Susan Preston-Martin; Thomas L. Vaughan; Wei Zheng; Paolo Boffetta

2002-01-01

14

A Pooled Analysis of Thyroid Cancer Incidence Following Radiotherapy for Childhood Cancer  

PubMed Central

Childhood cancer five-year survival now exceeds 70–80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9–14.9), 4.5 (1.4–17.8) and 3.2 (0.8–10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10–15-fold for 10–30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0–24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Veiga, Lene H. S.; Lubin, Jay H.; Anderson, Harald; de Vathaire, Florent; Tucker, Margaret; Bhatti, Parveen; Schneider, Arthur; Johansson, Robert; Inskip, Peter; Kleinerman, Ruth; Shore, Roy; Pottern, Linda; Holmberg, Erik; Hawkins, Michael M.; Adams, M. Jacob; Sadetzki, Siegal; Lundell, Marie; Sakata, Ritsu; Damber, Lena; Neta, Gila; Ron, Elaine

2012-01-01

15

A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer.  

PubMed

Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors. PMID:22857014

Veiga, Lene H S; Lubin, Jay H; Anderson, Harald; de Vathaire, Florent; Tucker, Margaret; Bhatti, Parveen; Schneider, Arthur; Johansson, Robert; Inskip, Peter; Kleinerman, Ruth; Shore, Roy; Pottern, Linda; Holmberg, Erik; Hawkins, Michael M; Adams, M Jacob; Sadetzki, Siegal; Lundell, Marie; Sakata, Ritsu; Damber, Lena; Neta, Gila; Ron, Elaine

2012-10-01

16

Chrysotile and Lung Cancer: Time-Related Effects and Pooled Analysis.  

National Technical Information Service (NTIS)

The project aimed to: conduct pooled analyses of the association of lung cancer with exposure to chrysotile asbestos in previously-enumerated cohorts of asbestos textile workers in North Carolina and South Carolina; evaluate exposure-time-response relatio...

D. Loomis D. Richardson J. Dement L. Elliott M. Lu

2011-01-01

17

International Lung Cancer Consortium: Pooled Analysis of Sequence Variants in DNA Repair and Cell Cycle Pathways  

PubMed Central

Background The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies. Methods Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects. Results Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79–0.99 and homozygote OR, 0.84; 95% CI, 0.71–1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89–1.10 and homozygote OR, 1.19; 95% CI, 1.02–1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00–1.29 and homozygote OR, 1.20; 95% CI, 1.02–1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01–1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk. Discussion In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies.

Hung, Rayjean J.; Christiani, David C.; Risch, Angela; Popanda, Odilia; Haugen, Aage; Zienolddiny, Shan; Benhamou, Simone; Bouchardy, Christine; Lan, Qing; Spitz, Margaret R.; Wichmann, H.-Erich; LeMarchand, Loic; Vineis, Paolo; Matullo, Giuseppe; Kiyohara, Chikako; Zhang, Zuo-Feng; Pezeshki, Benhnaz; Harris, Curtis; Mechanic, Leah; Seow, Adeline; Ng, Daniel P.K.; Szeszenia-Dabrowska, Neonila; Zaridze, David; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Caporaso, Neil; Chen, Chu; Duell, Eric J.; Goodman, Gary; Field, John K.; Houlston, Richard S.; Hong, Yun-Chul; Landi, Maria Teresa; Lazarus, Philip; Muscat, Joshua; McLaughlin, John; Schwartz, Ann G.; Shen, Hongbing; Stucker, Isabelle; Tajima, Kazuo; Matsuo, Keitaro; Thun, Michael; Yang, Ping; Wiencke, John; Andrew, Angeline S.; Monnier, Stephanie; Boffetta, Paolo; Brennan, Paul

2009-01-01

18

Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies  

PubMed Central

Purpose Although many studies have linked obesity with increased risk of thyroid cancer, few have investigated the role of obesity-related lifestyle characteristics and medical conditions in the etiology of this disease. We examined the associations of self-reported physical activity and diabetes history with thyroid cancer risk in a large pooled analysis of prospective cohort studies. Methods Data from five prospective studies in the U.S. (n=362,342 men, 312,149 women) were coded using standardized exposure, covariate, and outcome definitions. Hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer were estimated using age as the time metric and adjusting for sex, education, race, marital status, cigarette smoking, body mass index, alcohol intake, and cohort. Effect modification by other risk factors (e.g. age, sex, body mass index) and differences by cancer subtype (e.g. papillary, follicular) were also examined. Results Over follow-up (median=10.5 years), 308 men and 510 women were diagnosed with a first primary thyroid cancer. Overall, subjects reporting the greatest amount of physical activity had an increased risk of the disease (HR=1.18, 95% CI:1.00-1.39); however, this association was restricted to participants who were overweight/obese (?25 kg/m2; HR=1.34, 95% CI:1.09-1.64) as opposed to normal-weight (<25 kg/m2; HR=0.92, 95% CI:0.69-1.22; P-interaction=0.03). We found no overall association between self-reported history of diabetes and thyroid cancer risk (HR=1.08, 95% CI:0.83-1.40). Conclusion Neither physical inactivity nor diabetes history was associated with increased risk of thyroid cancer. While it may have been a chance finding, the possible increased risk associated with greater physical activity warrants further investigation.

Kitahara, Cari M.; Platz, Elizabeth A.; Beane Freeman, Laura E; Black, Amanda; Hsing, Ann W.; Linet, Martha S.; Park, Yikyung; Schairer, Catherine; Berrington de Gonzalez, Amy

2012-01-01

19

Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies  

PubMed Central

Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world’s published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for ?-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), ?-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). ?-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER?) than for ER+ tumors (eg, ?-carotene: ER?: top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER+: RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of ?-carotene, ?-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.

2012-01-01

20

Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts.  

PubMed

We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations. Cancer Res; 74(15); 4090-8. ©2014 AACR. PMID:24853549

Seow, Wei Jie; Cawthon, Richard M; Purdue, Mark P; Hu, Wei; Gao, Yu-Tang; Huang, Wen-Yi; Weinstein, Stephanie J; Ji, Bu-Tian; Virtamo, Jarmo; Hosgood, H Dean; Bassig, Bryan A; Shu, Xiao-Ou; Cai, Qiuyin; Xiang, Yong-Bing; Min, Shen; Chow, Wong-Ho; Berndt, Sonja I; Kim, Christopher; Lim, Unhee; Albanes, Demetrius; Caporaso, Neil E; Chanock, Stephen; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

2014-08-01

21

Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies  

PubMed Central

Background Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. Methods We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. Results Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. Conclusions We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation.

Sieh, Weiva; Salvador, Shannon; McGuire, Valerie; Weber, Rachel Palmieri; Terry, Kathryn L; Rossing, Mary Anne; Risch, Harvey; Wu, Anna H; Webb, Penelope M; Moysich, Kirsten; Doherty, Jennifer A; Felberg, Anna; Miller, Dianne; Jordan, Susan J; Goodman, Marc T; Lurie, Galina; Chang-Claude, Jenny; Rudolph, Anja; Kjaer, Susanne Kruger; Jensen, Allan; H?gdall, Estrid; Bandera, Elisa V; Olson, Sara H; King, Melony G; Rodriguez-Rodriguez, Lorna; Kiemeney, Lambertus A; Marees, Tamara; Massuger, Leon F; van Altena, Anne M; Ness, Roberta B; Cramer, Daniel W; Pike, Malcolm C; Pearce, Celeste Leigh; Berchuck, Andrew; Schildkraut, Joellen M; Whittemore, Alice S

2013-01-01

22

Re: HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials  

Microsoft Academic Search

Background Adjuvant chemotherapy with anthracyclines improves disease-free and overall survival compared with non - anthracycline-based adjuvant chemotherapy regimens in the treatment of early breast cancer. The role of HER2 status as a marker of anthracycline responsiveness has been explored by subset analy- ses within randomized clinical trials, with inconsistent results. We performed a pooled analysis of the interaction between HER2

RITA S. MEHTA; ALESSANDRA GENNARI; MARIA PIA SORMANI; PAOLO PRONZATO; PAOLO BRUZZI; Ulrich Pfeffer

2008-01-01

23

Intakes of fruit, vegetables, and carotenoids and renal cell cancer risk: a pooled analysis of 13 prospective studies  

PubMed Central

Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RRs) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with <200 g/d of fruit and vegetable intake, the pooled multivariate RR for ?600 g/d was 0.68 (95% CI = 0.54–0.87; P value, test for between-studies heterogeneity = 0.86; P value, test for trend = 0.001). Compared with <100 g/d, the pooled multivariate RRs (95% CIs) for ?400 g/d were 0.79 (0.63–0.99; P value, test for trend = 0.03) for total fruit, and 0.72 (0.48–1.08; P value, test for trend = 0.07) for total vegetables. For specific carotenoids, the pooled multivariate RRs (95% CIs) comparing the highest and lowest quintiles were 0.87 (0.73–1.03) for ?-carotene, 0.82 (0.69–0.98) for ?-carotene, 0.86 (0.73–1.01) for ?-cryptoxanthin, 0.82 (0.64–1.06) for lutein/zeaxanthin, and 1.13 (0.95–1.34) for lycopene. In conclusion, increasing fruit and vegetable consumption is associated with decreasing risk of renal cell cancer; carotenoids present in fruit and vegetables may partly contribute to this protection.

Lee, Jung Eun; Mannisto, Satu; Spiegelman, Donna; Hunter, David J.; Bernstein, Leslie; van den Brandt, Piet A.; Buring, Julie E.; Cho, Eunyoung; English, Dallas R.; Flood, Andrew; Freudenheim, Jo L.; Giles, Graham G.; Giovannucci, Edward; Hakansson, Niclas; Horn-Ross, Pamela L.; Jacobs, Eric J.; Leitzmann, Michael F.; Marshall, James R.; McCullough, Marjorie L.; Miller, Anthony B.; Rohan, Thomas E.; Ross, Julie A.; Schatzkin, Arthur; Schouten, Leo J.; Virtamo, Jarmo; Wolk, Alicja; Zhang, Shumin M.; Smith-Warner, Stephanie A.

2010-01-01

24

Sequence Variants and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium  

PubMed Central

Previous molecular epidemiological studies on head and neck cancer have examined various single nucleotide polymorphisms (SNPs), but there are very few documented associations. In the International head and neck cancer epidemiology (INHANCE) consortium, we evaluated associations between SNPs in the metabolism, cell cycle, and DNA repair pathways and the risk of head and neck cancer. We analyzed individual-level pooled data from 14 European, North American, Central American, and Asia case–control studies (5,915 head and neck cancer cases and 10,644 controls) participating in the INHANCE consortium. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for SNP effects, adjusting for age, sex, race, and country. We observed an association between head and neck cancer risk and MGMT Leu84Phe heterozygotes (OR?=?0.79, 95% CI?=?0.68–0.93), XRCC1 Arg194Trp homozygotes Arg/Arg (OR?=?2.3, 95% CI?=?1.1–4.7), ADH1B Arg48His homozygotes Arg/Arg (OR?=?2.7, 95% CI?=?1.9–4.0), ADH1C Ile350Val homozygotes Ile/Ile (OR?=?1.2, 95% CI?=?1.1–1.4), and the GSTM1 null genotype (OR?=?1.1, 95% CI?=?1.0–1.2). Among these results, MGMT Leu84Phe, ADH1B Arg48His, ADH1C Ile350Arg, and the GSTM1 null genotype had fairly low false positive report probabilities (<20%). We observed associations between ADH1B Arg48His, ADH1C Ile350Arg, and GSTM1 null genotype and head and neck cancer risk. No functional study currently supports the observed association for MGMT Leu84Phe, and the association with XRCC1 Arg194Trp may be a chance finding.

Chuang, Shu-Chun; Agudo, Antonio; Ahrens, Wolfgang; Anantharaman, Devasena; Benhamou, Simone; Boccia, Stefania; Chen, Chu; Conway, David I.; Fabianova, Eleonora; Hayes, Richard B.; Healy, Claire M.; Holcatova, Ivana; Kjaerheim, Kristina; Lagiou, Pagona; Lazarus, Philip; Macfarlane, Tatiana V.; Mahimkar, Manoj B.; Mates, Dana; Matsuo, Keitaro; Merletti, Franco; Metspalu, Andres; Morgenstern, Hal; Muscat, Joshua; Cadoni, Gabriella; Olshan, Andrew F.; Purdue, Mark; Ramroth, Heribert; Rudnai, Peter; Schwartz, Stephen M.; Simonato, Lorenzo; Smith, Elaine M.; Sturgis, Erich M.; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Thomson, Peter; Wei, Qingyi; Zaridze, David; Zhang, Zuo-Feng; Znaor, Ariana; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia

2011-01-01

25

Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010.  

PubMed

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

Olsson, Ann C; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

2013-11-01

26

The association between two polymorphisms in the TS gene and risk of cancer: a systematic review and pooled analysis.  

PubMed

Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA replication. Thymidylate synthase enhancer region (TSER) and TS1494del6, two functionally important and ethnically diverse polymorphisms mapping to its gene region, are the most extensively studied. Considering the potential influence of altering TS activity, it is plausible that TS polymorphisms might play a role in the development of cancer. Although the effects of TS polymorphisms on susceptibility to human cancer have been investigated in many studies, the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and cancer risk, including 63 studies (19,707 cases and 27,398 controls) for TSER polymorphism and 39 studies (13,489 cases and 16,297 controls) for TS1494del6 polymorphism. Our meta-analysis suggested that these two polymorphisms are not associated with cancer risk when all studies were pooled together. In the stratified analyses, we found that individuals with 2R/2R genotype had a significantly higher cancer risks among Asians (2R/2R vs. 3R/3R: odds ratio [OR] = 1.24, 95% confidence interval (95% CI) = 1.05-1.45; recessive model: OR = 1.23, 95% CI = 1.05-1.44). Further analyses revealed that 2R/2R genotype was significantly associated with an increased risk of gastroesophageal cancer among Asians, whereas it might provide protecting effects against colorectal cancer risk in a dominant genetic model for Caucasians. Additionally, TS1494del6 polymorphism may contribute to genetic susceptibility of breast cancer among Asians. PMID:22307944

Zhou, Jue-Yu; Shi, Rong; Yu, Hai-Lang; Zeng, Ye; Zheng, Wen-Ling; Ma, Wen-Li

2012-11-01

27

Revised Tumor and Node Categorization for Rectal Cancer Based on Surveillance, Epidemiology, and End Results and Rectal Pooled Analysis Outcomes  

PubMed Central

Purpose The sixth edition of the American Joint Committee on Cancer (AJCC) rectal cancer staging subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III as a result of improved survival with T1-2N2 versus T3-4N2 and survival of T4N1 more similar to T3-4N2 than T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival. Methods Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 35,829 patients with rectal cancer were compared with rectal pooled analysis data (3,791 patients). T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of positive nodes as follows: N1a/N1b (one v two to three nodes) and N2a/N2b (four to six v ? seven nodes). Five-year observed and relative survival rates were obtained for each TN category. Results SEER rectal cancer analyses confirm that T1-2N2 cancers have better prognosis than T3-4N2, T4bN1 have similar prognosis to T4N2, T1-2N1 have similar prognosis to T2N0/T3N0, and T1-2N2a have similar prognosis to T2N0/T3N0 (T1N2a) or T4aN0 (T2N2a). Prognosis for T4a lesions is better than T4b by N category. The number of positive nodes affects prognosis. Conclusion This SEER population-based rectal cancer analysis validates the rectal pooled analyses and supports the shift of T1-2N2 lesions from IIIC to IIIA or IIIB and T4bN1 from IIIB to IIIC. SEER outcomes support subdividing T4, N1, and N2 and revised substaging of stages II and III. Survival by TN category suggests a complex biologic interaction between depth of invasion and nodal status.

Gunderson, Leonard L.; Jessup, John Milburn; Sargent, Daniel J.; Greene, Frederick L.; Stewart, Andrew

2010-01-01

28

In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium  

PubMed Central

Background Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A). Objectives We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods Using questionnaire data, we classified subjects as predominant solid-fuel users (e.g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center. Results Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49–1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73–6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06–1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Conclusions Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations.

Hosgood, H. Dean; Boffetta, Paolo; Greenland, Sander; Lee, Yuan-Chin Amy; McLaughlin, John; Seow, Adeline; Duell, Eric J.; Andrew, Angeline S.; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Morgenstern, Hal; Rothman, Nathaniel; Hung, Rayjean J.; Brennan, Paul; Lan, Qing

2010-01-01

29

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies  

PubMed Central

Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13?226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13?226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45). Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne; Lee, Alice; Near, Aimee M; Webb, Penelope M; Nagle, Christina M; Doherty, Jennifer A; Cushing-Haugen, Kara L; Wicklund, Kristine G; Chang-Claude, Jenny; Hein, Rebecca; Lurie, Galina; Wilkens, Lynne R; Carney, Michael E; Goodman, Marc T; Moysich, Kirsten; Kjaer, Susanne K; Hogdall, Estrid; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Larson, Melissa C; Schildkraut, Joellen M; Palmieri, Rachel T; Cramer, Daniel W; Terry, Kathryn L; Vitonis, Allison F; Titus, Linda J; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Gentry-Maharaj, Alexandra; Ramus, Susan J; Anderson, A Rebecca; Brueggmann, Doerthe; Fasching, Peter A; Gayther, Simon A; Huntsman, David G; Menon, Usha; Ness, Roberta B; Pike, Malcolm C; Risch, Harvey; Wu, Anna H; Berchuck, Andrew

2012-01-01

30

COFFEE AND TEA INTAKE AND RISK OF HEAD AND NECK CANCER: POOLED ANALYSIS IN THE INTERNATIONAL HEAD AND NECK CANCER EPIDEMIOLOGY CONSORTIUM  

PubMed Central

Background Only a few studies have explored the relation between coffee and tea intake and head and neck (HN) cancers, with inconsistent results. Methods We pooled individual-level data from nine case-control studies of HN cancers, including 5139 cases and 9028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for potential confounders. Results Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx (OP): the ORs were 0.96 (95% CI 0.94–0.98) for an increment of one cup per day and 0.61 (95% CI 0.47–0.80) in drinkers of >4 cups per day vs. non-drinkers. This latter estimate was consistent for different anatomical sites (ORs were 0.46, 95%CI 0.30–0.71 for oral cavity, 0.58, 95% CI 0.41–0.82 for oropharyngeal/hypopharyngeal and 0.61, 95% CI 0.37–1.01 for OP not otherwise specified), and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR=0.96, 95% CI 0.64–1.45 in drinkers of >4 cups per day vs. non-drinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with HN cancer risk (OR=0.99, 95% CI 0.89–1.11 for drinkers vs. non-drinkers). Conclusions This pooled-analysis of case-control studies support the hypothesis of an inverse association between caffeinated coffee drinking and OP cancer risk. Impact Given widespread use of coffee and the relatively high incidence and low survival of HN cancers, the observed inverse association may have appreciable public health relevance.

Galeone, Carlotta; Tavani, Alessandra; Pelucchi, Claudio; Turati, Federica; Winn, Deborah M.; Levi, Fabio; Yu, Guo-Pei; Morgenstern, Hal; Kelsey, Karl; Maso, Luigino Dal; Purdue, Mark P.; McClean, Michael; Talamini, Renato; Hayes, Richard B.; Franceschi, Silvia; Schantz, Stimson; Zhang, Zuo-Feng; Ferro, Gilles; Chuang, Shu-Chun; Boffetta, Paolo; La Vecchia, Carlo; Hashibe, Mia

2011-01-01

31

Proposing the lymphatic target volume for elective radiation therapy for pancreatic cancer: a pooled analysis of clinical evidence  

PubMed Central

Background Radiation therapy is an important cancer treatment modality in both adjuvant and definitive setting, however, the use of radiation therapy for elective treatment of regional lymph nodes is controversial for pancreatic cancer. No consensus on proper selection and delineation of subclinical lymph nodal areas in adjuvant or definitive radiation therapy has been suggested either conclusively or proposed for further investigation. This analysis aims to study the pattern of lymph node metastasis through a pooled analysis of published results after radical tumor and lymph nodal resection with histological study in pancreatic cancer. Methods Literature search using electronic databases including MEDLINE, EMBASE, and CANCERLIT from January 1970 to June 2009 was performed, supplemented by review of references. Eighteen original researches and a total of 5954 pancreatic cancer patients underwent radical surgical resection were included in this analysis. The probability of metastasis in regional lymph nodal stations (using Japan Pancreas Society [JPS] Classification) was calculated and analyzed based on the location and other characteristics of the primary disease. Results Commonly involved nodal regions in patients with pancreatic head tumor include lymph nodes around the common hepatic artery (Group 8, 9.79%), posterior pancreaticoduodenal lymph nodes (Group 13, 32.31%), lymph nodes around the superior mesenteric artery (Group 14, 15.85%), paraaortic lymph nodes (Group 16, 10.92%), and anterior pancreaticoduodenal lymph nodes (Group 17, 19.78%); The probability of metastasis in other lymph nodal regions were <9%. Commonly involved nodal regions in patients with pancreatic body/tail tumor include lymph nodes around the common hepatic artery (Group 8, 15.07%), lymph nodes around the celiac trunk (Group 9, 9.59%), lymph nodes along the splenic artery (Group 11, 35.62%), lymph nodes around the superior mesenteric artery (Group 14, 9.59%), paraaortic lymph nodes (Group 16, 16.44%), and inferior body lymph nodes (Group 18, 24.66%). The probability of metastasis in other lymph nodal regions were <9%. Conclusions Pancreatic cancer has a high propensity of regional lymphatic metastases; however, clear patterns including the site and probability of metastasis can be identified and used as a guide of treatment in patients with resectable pancreatic cancer. Further clinical investigation is needed to study the efficacy of elective treatment to CTV defined based on these patterns using high-dose conformal or intensity-modulated radiation therapy.

2010-01-01

32

Green tea consumption and gastric cancer in Japanese: a pooled analysis of six cohort studies  

Microsoft Academic Search

Background:Previous experimental studies have suggested many possible anti-cancer mechanisms for green tea, but epidemiological evidence for the effect of green tea consumption on gastric cancer risk is conflicting.Objective:To examine the association between green tea consumption and gastric cancer.Methods:We analysed original data from six cohort studies that measured green tea consumption using validated questionnaires at baseline. Hazard ratios (HRs) in the

M Inoue; S Sasazuki; K Wakai; T Suzuki; K Matsuo; T Shimazu; I Tsuji; K Tanaka; T Mizoue; C Nagata; A Tamakoshi; N Sawada; S Tsugane

2009-01-01

33

Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium  

PubMed Central

Background and Methods Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analyzed. Unconditional logistic regression models and generalized estimating equations were used to estimate odds ratios and 95% confidence intervals. Results Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in risk of lung cancer, after adjustment for smoking and other potential confounders(95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (OR=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions The increased risk among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those associated with cigarette smoking. While the role of genetic variation in the etiology of lung cancer remains to be fully characterized, family history assessment is immediately available and those with a positive history represent a higher risk group.

Cote, Michele L.; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G.; Christiani, David C.; Spitz, Margaret R.; Muscat, Joshua E.; Rennert, Gad; Aben, Katja K.; Andrew, Angeline S.; Bencko, Vladimir; Bickeboller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J.; Fabianova, Eleonora; Field, John K.; Foretova, Lenka; Friis, S?ren; Harris, Curtis C.; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A.; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Marchand, Loic Le; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I.; McLaughlin, John R.; Morgenstern, Hal; Mueller, Heiko; Orlow, Irene; Park, Bernard J.; Pinchev, Mila; Raji, Olaide Y.; Rennert, Hedy S.; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Teare, M. Dawn; Tj?nnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F.M.; Wichmann, Erich; Wiencke, John K.; Woll, Penella J.; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J.; Hung, Rayjean J.

2012-01-01

34

Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies  

Microsoft Academic Search

Background More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consump- tion and to assess whether non-dietary risk factors modify the relation. Methods We combined the primary data from eight prospective cohort

Stacey A Missmer; Stephanie A Smith-Warner; Donna Spiegelman; Shiaw-Shyuan Yaun; P. A. van den Brandt

2002-01-01

35

Welding and lung cancer in a pooled analysis of case-control studies.  

PubMed

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. PMID:24052544

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; 't Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-11-15

36

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies  

Microsoft Academic Search

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein þ zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in

Satu Mannisto; Shiaw-Shyuan Yaun; David J. Hunter; Donna Spiegelman; Hans-Olov Adami; Demetrius Albanes; Brandt van den Piet A; Julie E. Buring; James R. Cerhan; Graham A. Colditz; Jo L. Freudenheim; Charles S. Fuchs; Edward Giovannucci; R. Alexandra Goldbohm; Lisa Harnack; Michael Leitzmann; Marjorie L. McCullough; Anthony B. Miller; Thomas E. Rohan; Arthur Schatzkin; Jarmo Virtamo; Walter C. Willett; Alicja Wolk; Shumin M. Zhang; Stephanie A. Smith-Warner

2007-01-01

37

Pooled Bayesian analysis of twenty-eight studies on radon induced lung cancers.  

PubMed

The influence of ionizing radiation of (222)Rn and its progeny on lung cancer risks that were published in 28 papers was re-analyzed using seven alternative dose-response models. The risks of incidence and mortality were studied in two ranges of low annual radiation dose: 0-70 mSv per year (391 Bq m(-3)) and 0-150 mSv per year (838 Bq m(-3)). Assumption-free Bayesian statistical methods were used. The analytical results demonstrate that the published incidence and mortality data do not show that radiation dose is associated with increased risk in this range of doses. This conclusion is based on the observation that the model assuming no dependence of the lung cancer induction on the radiation doses is at least ?90 times more likely to be true than the other models tested, including the linear no-threshold (LNT) model. PMID:21799343

Fornalski, Krzysztof Wojciech; Dobrzy?ski, Ludwik

2011-09-01

38

Single-port laparoscopic colorectal cancer surgery in Korea: retrospective analysis of the multicenter, pooled database.  

PubMed

Abstract Introduction: Single-port laparoscopic surgery (SPLS), one of the advanced techniques of laparoscopic surgery, is performed through a single multichannel port. Regarding colorectal surgery, several colorectal procedures, including right colectomy, sigmoidectomy, and total proctocelectomy with ileal pouch anal anastomosis, have been performed successfully. The aim of this study was to elucidate the feasibility and safety of SPLS for the treatment of the patient with colorectal cancer in Korea. Subjects and Methods: Data were collected retrospectively from six hospitals through a Web-based case reporting form, which requested baseline characteristics of the patient, intraoperative findings, postoperative course, pathologic results of the tumor, and postoperative surveillance. Results: From May 2009 to June 2012, 257 patients were included in this study. Anterior resection was performed in 117 patients, low anterior resection in 66 patients, and right colectomy in 53 patients. The primary entry incision site was umbilicus in all patients except for 2 cases; in these, stoma sites were used for the entry of the single port. The total mean incision length was 3.8±2.3?cm. Among 257 initially SPLS-attempted patients, 45 (17.5%) patients needed additional ports (one additional port in 44 patients), and 2 patients (0.78%) had to be converted to open laparotomy. Intraoperative complications were noted in 5 patients, including anastomotic failures in 3 patients and bleeding in 1 patient. Postoperative complications were noted in 34 patients (13.2%). Anastomotic leak developed in 11 patients, urinary retention in 5 patients, and wound complications in 4 patients. Re-admission was needed in 15 patients (5.8%). Conclusions: SPLS could be performed safely and appropriately in selected colorectal cancer cases by experts in laparoscopic colorectal surgery in Korea. Prospective randomized trials to demonstrate the benefit and effectiveness of SPLS in colorectal cancer surgery with long-term oncologic results are needed. PMID:24818648

Kim, Hyung Jin; Kang, Byung Mo; Lee, Suk-Hwan; Lee, Sang Chul; Lee, Kil Yeon; Park, Sun Jin; Lim, Sang Woo; Kim, Jun-Gi

2014-07-01

39

Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method  

PubMed Central

Background Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings. Methods We compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13?140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided. Results Of 13?004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing. Conclusions The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.

Zhao, Fang-Hui; Lewkowitz, Adam K.; Chen, Feng; Lin, Margaret J.; Hu, Shang-Ying; Zhang, Xun; Pan, Qin-Jing; Ma, Jun-Fei; Niyazi, Mayineur; Li, Chang-Qing; Li, Shu-Min; Smith, Jennifer S.; Belinson, Jerome L.; Castle, Philip E.

2012-01-01

40

Meta- and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oropharyngeal cancer: a HuGE-GSEC review  

PubMed Central

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9–3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9–1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4–2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3–3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1–1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1–4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer.

Varela-Lema, L; Taioli, E; Ruano-Ravina, A; Barros-Dios, JM; Benhamou, S; Bhisey, RA; Chen, CJ; Coutelle, C; Foulkes, W.D; Hayes, RB; Katoh, T; Lazarus, P; Manni, JJ; Morita, S; Park, JY; Roy, B; Spitz, MR; Strange, RC; Wei, Q; Ragin, C

2014-01-01

41

Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case–control studies  

Microsoft Academic Search

Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection

N Costet; C M Villanueva; J J K Jaakkola; M Kogevinas; K P Cantor; W D King; C F Lynch; M J Nieuwenhuijsen; S Cordier

2011-01-01

42

Data Pooling and Analysis to Build a Preliminary Item BankAn Example Using Bowel Function in Prostate Cancer  

Microsoft Academic Search

Assessing bowel function (BF) in prostate cancer can help determine therapeutic trade-offs. We determined the components of BF commonly assessed in prostate cancer studies as an initial step in creating an item bank for clinical and research application. We analyzed six archived data sets representing 4,246 men with prostate cancer. Thirty-one items from validated instruments were available for analysis. Items

David T. Eton; Jin-Shei Lai; David Cella; Bryce B. Reeve; James A. Talcott; Jack A. Clark; Carol P. McPherson; Mark S. Litwin; Carol M. Moinpour

2005-01-01

43

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium  

PubMed Central

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case–control studies for 11?645 lung cancer case patients and 14?954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10?26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10?10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10?8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10?5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Truong, Therese; Hung, Rayjean J.; Amos, Christopher I.; Wu, Xifeng; Bickeboller, Heike; Rosenberger, Albert; Sauter, Wiebke; Illig, Thomas; Wichmann, H.-Erich; Risch, Angela; Dienemann, Hendrik; Kaaks, Rudolph; Yang, Ping; Jiang, Ruoxiang; Wiencke, John K.; Wrensch, Margaret; Hansen, Helen; Kelsey, Karl T.; Matsuo, Keitaro; Tajima, Kazuo; Schwartz, Ann G.; Wenzlaff, Angie; Seow, Adeline; Ying, Chen; Staratschek-Jox, Andrea; Nurnberg, Peter; Stoelben, Erich; Wolf, Jurgen; Lazarus, Philip; Muscat, Joshua E.; Gallagher, Carla J.; Zienolddiny, Shanbeh; Haugen, Aage; van der Heijden, Henricus F. M.; Kiemeney, Lambertus A.; Isla, Dolores; Mayordomo, Jose Ignacio; Rafnar, Thorunn; Stefansson, Kari; Zhang, Zuo-Feng; Chang, Shen-Chih; Kim, Jin Hee; Hong, Yun-Chul; Duell, Eric J.; Andrew, Angeline S.; Lejbkowicz, Flavio; Rennert, Gad; Muller, Heiko; Brenner, Hermann; Le Marchand, Loic; Benhamou, Simone; Bouchardy, Christine; Teare, M. Dawn; Xue, Xiaoyan; McLaughlin, John; Liu, Geoffrey; McKay, James D.; Spitz, Margaret R.

2010-01-01

44

Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies.  

PubMed

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development. PMID:22052329

Pesch, Beate; Kendzia, Benjamin; Gustavsson, Per; Jöckel, Karl-Heinz; Johnen, Georg; Pohlabeln, Hermann; Olsson, Ann; Ahrens, Wolfgang; Gross, Isabelle Mercedes; Brüske, Irene; Wichmann, Heinz-Erich; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Fortes, Cristina; Siemiatycki, Jack; Parent, Marie-Elise; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Zaridze, David; Cassidy, Adrian; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Stücker, Isabelle; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudin, Charles M; Brennan, Paul; Boffetta, Paolo; Straif, Kurt; Brüning, Thomas

2012-09-01

45

Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference in-gel electrophoresis analysis of pooled clinical samples  

PubMed Central

Introduction: Ovarian cancer is the leading cause of death from gynecological cancer. Non-specific symptoms early in disease and the lack of specific biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown promise for improving identification of early stage disease; however, available tests lack sensitivity, and specificity. Materials and Methods: In this study, pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and healthy controls were used to compare the 2-dimensional gel electrophoresis (2-DE) protein profiles and identify potential novel markers of ovarian cancer progression. Results/Discussion: Stage-specific variation in biomarker expression was observed. For example, apolipoprotein A1 expression is relatively low in control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus, potential of utility for disease confirmation rather than early detection. A better marker for early stage disease was tropomyosin 4 (TPM4). The expression of TPM4 increased by 2-fold in Stage 2 before returning to “normal” levels in Stage 3 disease. Multiple isoforms were also identified for some proteins and in some cases, displayed stage-specific expression. An interesting example was fibrinogen alpha, for which 8 isoforms were identified. Four displayed a moderate increase at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed only moderate increases. Conclusion: Herein is provided an improved summary of blood protein profiles for women with ovarian cancer stratified by stage.

Bailey, Mark J.; Shield-Artin, Kristy L.; Oliva, Karen; Ayhan, Mustafa; Reisman, Simone; Rice, Gregory E.

2013-01-01

46

The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: a pooled analysis of 41 sets of data from case-control studies.  

PubMed

Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768-0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa. PMID:24177231

Chen, Yang; Li, Tianyu; Yu, Xiaoqiang; Xu, Jianfeng; Li, Jianling; Luo, Dexiang; Mo, Zengnan; Hu, Yanling

2014-01-25

47

Analysis of deoxyribonucleotide pools in human cancer cell lines using a liquid chromatography coupled with tandem mass spectrometry technique  

PubMed Central

Endogenous ribonucleotides and deoxyribonucleotides play a critical role in cell function, and determination of their levels is of fundamental importance in understanding key cellular processes involved in energy metabolism and molecular and biochemical signaling pathways. In this study, we determined the respective ribonucleotide and deoxyribonucleotide pool sizes in different human cell lines using a simple sample preparation method and LC/MS/MS. This assay was used to determine alterations in deoxyribonucleotide pools in human pancreatic PANC-1 cells in response to hypoxia and to treatment with either hydroxyurea or aphidicolin. The levels of all deoxyribonucleotide metabolites decreased with hypoxia treatment, except for dUMP, which increased by two-fold. This LC/MS/MS assay is simple, fast, and sensitive, and it represents a significant advance over previously published methodologies.

Zhang, Wei; Tan, Shenglan; Paintsil, Elijah; Dutschman, Ginger E.; Gullen, Elizabeth A.; Chu, Edward; Cheng, Yung-Chi

2011-01-01

48

Association between SPARC mRNA Expression, Prognosis and Response to Neoadjuvant Chemotherapy in Early Breast Cancer: A Pooled in-silico Analysis  

PubMed Central

Introduction SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC). Methods We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7), composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1) expression of SPARC/SPARC7 according to breast cancer subtype, 2) association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3) association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors. Results 948 (10 datasets), and 791 (8 datasets) patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p<0.0001). There was a positive correlation between SPARC and stroma-related modules but negative correlation with proliferation modules. High SPARC expression was associated with poor prognosis in patients with basal and HER2+ breast cancer even after adjusting for clinicopathologic parameters. In the neoadjuvant cohort, a subgroup analysis suggested that high SPARC is associated with low rates of pCR in the HER2 subtype. Same results were observed on replacing SPARC by SPARC7. Conclusion This analysis suggests a potential role of SPARC in determining prognosis and response to primary chemotherapy in early BC. This information could guide further development of albumin-bound cytotoxics in BC.

Ignatiadis, Michail; Desmedt, Christine; Fumagalli, Debora; Veys, Isabelle; Larsimont, Denis; Piccart, Martine; Michiels, Stefan; Sotiriou, Christos

2013-01-01

49

Proposing the lymphatic target volume for elective radiation therapy for pancreatic cancer: a pooled analysis of clinical evidence  

Microsoft Academic Search

BACKGROUND: Radiation therapy is an important cancer treatment modality in both adjuvant and definitive setting, however, the use of radiation therapy for elective treatment of regional lymph nodes is controversial for pancreatic cancer. No consensus on proper selection and delineation of subclinical lymph nodal areas in adjuvant or definitive radiation therapy has been suggested either conclusively or proposed for further

Wenjie Sun; Cheng N Leong; Zhen Zhang; Jiade J Lu

2010-01-01

50

The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case-control studies  

PubMed Central

Background The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting. Methods To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism. Results The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55). The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646). Conclusions Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not.

2013-01-01

51

Breast cancer risk after radiotherapy in infancy: a pooled analysis of two Swedish cohorts of 17,202 infants.  

PubMed

The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies. PMID:10319736

Lundell, M; Mattsson, A; Karlsson, P; Holmberg, E; Gustafsson, A; Holm, L E

1999-05-01

52

Ixabepilone plus capecitabine in metastatic breast cancer patients with reduced performance status previously treated with anthracyclines and taxanes: a pooled analysis by performance status of efficacy and safety data from 2 phase III studies  

Microsoft Academic Search

Patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes often have decreased performance\\u000a status secondary to extensive tumor involvement. Here, we report the pooled analysis of efficacy and safety data from two\\u000a similarly designed phase III studies to provide a more precise estimate of benefit of ixabepilone plus capecitabine in MBC\\u000a patients with Karnofsky’s performance status (KPS)

Henri Roche ´; Pierfranco Conte; Edith A. Perez; Joseph A. Sparano; Binghe Xu; Jacek Jassem; Ronald Peck; Thomas Kelleher; Gabriel N. Hortobagyi

2011-01-01

53

The After Breast Cancer Pooling Project: rationale, methodology, and breast cancer survivor characteristics  

Microsoft Academic Search

The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors,\\u000a supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis\\u000a lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer\\u000a survivors (three US-based and one from

Sarah J. Nechuta; Bette J. Caan; Wendy Y. Chen; Shirley W. Flatt; Wei Lu; Ruth E. Patterson; Elizabeth M. Poole; Marilyn L. Kwan; Zhi Chen; Erin Weltzien; John P. Pierce; Xiao Ou Shu

2011-01-01

54

Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium  

Microsoft Academic Search

BACKGROUND: Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in

T. Truong; R. J. Hung; C. I. Amos; X. Wu; H. Bickeboller; A. Rosenberger; W. Sauter; T. Illig; H.-E. Wichmann; A. Risch; H. Dienemann; R. Kaaks; P. Yang; R. Jiang; J. K. Wiencke; M. Wrensch; H. Hansen; K. T. Kelsey; K. Matsuo; K. Tajima; A. G. Schwartz; A. Wenzlaff; A. Seow; C. Ying; A. Staratschek-Jox; P. Nurnberg; E. Stoelben; J. Wolf; P. Lazarus; J. E. Muscat; C. J. Gallagher; S. Zienolddiny; A. Haugen; H. F. M. van der Heijden; L. A. L. M. Kiemeney; D. Isla; J. I. Mayordomo; T. Rafnar; K. Stefansson; Z.-F. Zhang; S.-C. Chang; J. H. Kim; Y.-C. Hong; E. J. Duell; A. S. Andrew; F. Lejbkowicz; G. Rennert; H. Muller; H. Brenner; L. le Marchand; S. Benhamou; C. Bouchardy; M. D. Teare; X. Xue; J. McLaughlin; G. Liu; J. D. McKay; P. Brennan; M. R. Spitz

2010-01-01

55

Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees  

PubMed Central

Background Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann–Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. Results The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence… Conclusions The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence.

2013-01-01

56

Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls.  

PubMed

Genital powder use has been associated with risk of epithelial ovarian cancer in some, but not all, epidemiologic investigations, possibly reflecting the carcinogenic effects of talc particles found in most of these products. Whether risk increases with number of genital powder applications and for all histologic types of ovarian cancer also remains uncertain. Therefore, we estimated the association between self-reported genital powder use and epithelial ovarian cancer risk in eight population-based case-control studies. Individual data from each study were collected and harmonized. Lifetime number of genital powder applications was estimated from duration and frequency of use. Pooled ORs were calculated using conditional logistic regression matched on study and age and adjusted for potential confounders. Subtype-specific risks were estimated according to tumor behavior and histology. 8,525 cases and 9,859 controls were included in the analyses. Genital powder use was associated with a modest increased risk of epithelial ovarian cancer [OR, 1.24; 95% confidence interval (CI), 1.15-1.33] relative to women who never used powder. Risk was elevated for invasive serous (OR, 1.20; 95% CI, 1.09-1.32), endometrioid (OR, 1.22; 95% CI, 1.04-1.43), and clear cell (OR, 1.24; 95% CI, 1.01-1.52) tumors, and for borderline serous tumors (OR, 1.46; 95% CI, 1.24-1.72). Among genital powder users, we observed no significant trend (P = 0.17) in risk with increasing number of lifetime applications (assessed in quartiles). We noted no increase in risk among women who only reported nongenital powder use. In summary, genital powder use is a modifiable exposure associated with small-to-moderate increases in risk of most histologic subtypes of epithelial ovarian cancer. PMID:23761272

Terry, Kathryn L; Karageorgi, Stalo; Shvetsov, Yurii B; Merritt, Melissa A; Lurie, Galina; Thompson, Pamela J; Carney, Michael E; Weber, Rachel Palmieri; Akushevich, Lucy; Lo-Ciganic, Wei-Hsuan; Cushing-Haugen, Kara; Sieh, Weiva; Moysich, Kirsten; Doherty, Jennifer A; Nagle, Christina M; Berchuck, Andrew; Pearce, Celeste L; Pike, Malcolm; Ness, Roberta B; Webb, Penelope M; Rossing, Mary Anne; Schildkraut, Joellen; Risch, Harvey; Goodman, Marc T

2013-08-01

57

Use of Pooled Probes in Genetic Analysis.  

National Technical Information Service (NTIS)

The invention provides arrays of polynucleotide probes having at least one pooled position. A typical array comprises a support having at least three discrete regions. A first region bears a pool of polynucleotide probes comprising first and second probes...

E. Gentalen M. Chee

2005-01-01

58

Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts  

PubMed Central

Background There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. Methods The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. Results In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR]?=?0.68, 95% CI 0.52–0.89) and cancer (HR?=?0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Conclusions Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.

Stamatakis, Emmanuel; Chau, Josephine Y.; Pedisic, Zeljko; Bauman, Adrian; Macniven, Rona; Coombs, Ngaire; Hamer, Mark

2013-01-01

59

Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium  

PubMed Central

Background Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. Methods We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR) and 95% confidence intervals (CI) according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. Results Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8?oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08). This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02), although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09). Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. Conclusions We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community.

2013-01-01

60

Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor.  

PubMed

Fibroblast growth factor receptor 4 (FGFR4) contains a Gly388Arg functional polymorphism (rs351855) that has shown contrasting results in association studies. In this study, we assessed the association between the FGFR4 Gly388Arg polymorphism and cancer prognosis. Meta-analysis and pooled analysis of 6817 and 2537 cancer cases, respectively, were carried out by nodal status and overall survival. The study included the following types of cancer: brain, breast, colorectal, head and neck, larynx, lung, melanoma, prostate, sarcomas. A statistically significant association between the Arg388Arg genotype and nodal involvement was found in the meta-analysis (odds ratio=1.33, 95% confidence interval 1.01-1.74). In the pooled analysis, the Arg388 allele carriers showed an increased hazard of poor overall survival compared with homozygous carriers of the common Gly388 allele, even after adjusting for nodal status (hazard ratio=1.21, 95% confidence interval 1.05-1.40). These results provide evidence of a role for the FGFR4 Gly388Arg polymorphism in modulating patients' outcome in different types of cancer, thus offering to clinicians a new marker to predict predisposition to poor survival in cancer patients. PMID:21412156

Frullanti, Elisa; Berking, Carola; Harbeck, Nadia; Jézéquel, Pascal; Haugen, Aage; Mawrin, Christian; Parise, Orlando; Sasaki, Hidefumi; Tsuchiya, Norihiko; Dragani, Tommaso A

2011-07-01

61

Sorafenib-based therapy in HER2-negative advanced breast cancer: Results from a retrospective pooled analysis of randomized controlled trials  

PubMed Central

A standard systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) is yet to be identified. Sorafenib has been developed for the treatment of solid tumors, including breast cancer, as an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. The aim of the present study was to assess the efficacy and safety of sorafenib in patients with HER2-negative ABC by performing a meta-analysis. A literature search was applied to databases, including PubMed, EMBASE, the Cochrane Library Databases, American Society of Clinical Oncology and the European Society for Medical Oncology, with the search terms ‘advanced breast cancer’ and ‘sorafenib’ and relevant studies were selected for analysis. The data extracted from the selected studies included progression-free survival (PFS), time to progression (TTP), overall survival (OS) and overall response rate (ORR). Major adverse events (AEs) were also analyzed. A total of four randomized controlled trials containing 844 cases were identified. Combined results revealed that when compared with chemotherapy (or with anti-hormone receptor therapy) alone, sorafenib-based therapy significantly increased the PFS [hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.54–1.02] and TTP (HR, 0.74; 95% CI, 0.50–0.97), but not the OS (HR, 0.95; 95% CI, 0.75–1.15) and ORR (relative risk, 1.19; 95% CI, 1.01–1.39). In addition, the incidence of grade 3/4 AEs, including hand-foot skin syndrome, anemia, fatigue, rash and stomatitis, were significantly increased in patients that received sorafenib-based therapy. Therefore, the results from the current meta-analysis indicated that sorafenib-based therapy improved the PFS and TTP in patients with HER2-negative ABC, but not the OS and ORR. In addition, combination treatment was associated with increased toxicities and frequently required dose reductions.

TAN, QI-XING; QIN, QING-HONG; LIAN, BIN; YANG, WEI-PING; WEI, CHANG-YUAN

2014-01-01

62

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis  

PubMed Central

Introduction Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. Methods We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. Results Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI?

2013-01-01

63

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214  

SciTech Connect

Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.

Gondi, Vinai, E-mail: vgondi@chicagocancer.org [Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States) [Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States); University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States)] [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Bruner, Deborah W. [Nell Hodgson Woodfull School of Nursing, Emory University, Atlanta, Georgia (United States)] [Nell Hodgson Woodfull School of Nursing, Emory University, Atlanta, Georgia (United States); Meyers, Christina A. [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gore, Elizabeth M. [Medical College of Wisconsin, Milwaukee, Wisconsin (United States)] [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wolfson, Aaron [University of Miami School of Medicine, Miami, Florida (United States)] [University of Miami School of Medicine, Miami, Florida (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)] [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Sun, Alexander Y. [Princess Margaret Hospital, Toronto, ON (Canada)] [Princess Margaret Hospital, Toronto, ON (Canada); Choy, Hak [University of Texas Southwestern Moncreif Cancer Center, Fort Worth, Texas (United States)] [University of Texas Southwestern Moncreif Cancer Center, Fort Worth, Texas (United States); Movsas, Benjamin [Henry Ford Health System, Detroit, Michigan (United States)] [Henry Ford Health System, Detroit, Michigan (United States)

2013-07-15

64

Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients  

Microsoft Academic Search

BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor\\u000a (PAI-1) play essential roles in tumor invasion and metastasis. High levels\\u000a of both uPA and PAI-1 are associated with poor prognosis in breast cancer\\u000a patients. To confirm the prognostic value of uPA and PAI-1 in primary\\u000a breast cancer, we reanalyzed individual patient data provided by members\\u000a of the European Organization for Research

Maxime P. Look; W. Kueng; J. G. M. Klijn; P. Broet; U. Eppenberger; Putten van W. L. J; M. Ferno; I. J. Christensen; B. W. Lisboa; C. Thomssen; R. Kates; H. Magdelenat; Pierre-Marie Martin; L. V. Beex; G. Windbichler; F. Janicke; F. Spyratos; J. P. Peyrat; G. Ricolleau; T. Cufer; N. Brunner; Marion E. Meijer-van Gelder; P. O. Bendahl; K. Ulm; M. Schmitt; S. Eppenberger-Castori; C. G. Sweep; W. E. Fiets; C. Duggan; M. A. Blankenstein; Simona Borstnar; G. Daxenbichler; J. A. Foekens; N. O'Higgins; M. J. Duffy; A. Daver; P. Manders; S. Romain; V. Quillien; N. Harbeck

2002-01-01

65

Pooled analysis of data from multiple quantitative trait locus mapping populations  

Microsoft Academic Search

Quantitative trait locus (QTL) analysis on pooled data from multiple populations (pooled analysis) provides a means for evaluating, as a whole, evidence for existence of a QTL from different studies and examining differences in gene effect of a QTL among different populations. Objectives of this study were to: (1) develop a method for pooled analysis and (2) conduct pooled analysis

B. Guo; D. A. Sleper; J. Sun; H. T. Nguyen; P. R. Arelli; J. G. Shannon

2006-01-01

66

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials  

Microsoft Academic Search

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether\\u000a characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity\\u000a in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials\\u000a with uniform protocols. PCR was associated with

Gunter von Minckwitz; Michael Untch; Eveline Nüesch; Sibylle Loibl; Manfred Kaufmann; Sherko Kümmel; Peter A. Fasching; Wolfgang Eiermann; Jens-Uwe Blohmer; Serban Dan Costa; Keyur Mehta; Jörn Hilfrich; Christian Jackisch; Bernd Gerber; Andreas du Bois; Jens Huober; Claus Hanusch; Gottfried Konecny; Werner Fett; Elmar Stickeler; Nadia Harbeck; Volkmar Müller; Peter Jüni

2011-01-01

67

KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials  

SciTech Connect

Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.

Kim, Sun Young; Shim, Eun Kyung [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Yeo, Hyun Yang [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of) [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Won [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jee Hyun [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of)] [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Im, Seock-Ah [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)] [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Kyung Hae [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chang, Hee Jin, E-mail: heejincmd@yahoo.com [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

2013-01-01

68

Pooled Analysis of Loss of Heterozygosity in Breast Cancer: a Genome Scan Provides Comparative Evidence for Multiple Tumor Suppressors and Identifies Novel Candidate Regions  

PubMed Central

Somatic loss of heterozygosity (LOH) has been widely reported in breast cancer as a means of identifying putative tumor-suppressor genes. However, individual studies have rarely spanned more than a single chromosome, and the varying criteria used to declare LOH complicate efforts to formally differentiate regions of consistent versus sporadic (random) loss. We report here the compilation of an extensive database from 151 published LOH studies of breast cancer, with summary data from >15,000 tumors and primary allelotypes from >4,300 tumors. Allelic loss was evaluated at 1,168 marker loci, with large variation in the density of informative observations across the genome. Using studies in which primary allelotype information was available, we employed a likelihood-based approach with a formal chromosomal instability and selection model. The approach seeks direct evidence for preferential loss at each locus compared with nearby loci, accounts for heterogeneity across studies, and enables the direct comparison of candidate regions across the genome. Striking preferential loss was observed (in descending order of significance) in specific regions of chromosomes 7q, 16q, 13q, 17p, 8p, 21q, 3p, 18q, 2q, and 19p, as well as other regions, in many cases coinciding with previously identified candidate genes or known fragile sites. Many of these observations were not possible from any single LOH study, and our results suggest that many previously reported LOH results are not systematic or reproducible. Our approach provides a comparative framework for further investigation of regions exhibiting LOH and identifies broad genomic regions for which there exist few data.

Miller, Brian J.; Wang, Daolong; Krahe, Ralf; Wright, Fred A.

2003-01-01

69

Analysis of Swimming Pool Water - Assessment of Results According to German Regulations  

Microsoft Academic Search

In Germany, quality of swimming pool water is regulated by DIN19643. In this paper we present results of microbiological and chemical analysis of pool water and show correlations between parameters. In total, more than 500 pool analysis from 100 different pools have been performed within a two-year period. Results have been evaluated using statistical methods. Next to microbiological parameters (Colony

Lothar Erdinger; Frank Kirsch; Thomas Gabrio; Klaus P. Kühn

70

Likelihood-based methods for regression analysis with binary exposure status assessed by pooling  

PubMed Central

The need for resource-intensive laboratory assays to assess exposures in many epidemiologic studies provides ample motivation to consider study designs that incorporate pooled samples. In this paper, we consider the case in which specimens are combined for the purpose of determining the presence or absence of a pool-wise exposure, in lieu of assessing the actual binary exposure status for each member of the pool. We presume a primary logistic regression model for an observed binary outcome, together with a secondary regression model for exposure. We facilitate maximum likelihood analysis by complete enumeration of the possible implications of a positive pool, and we discuss the applicability of this approach under both cross-sectional and case-control sampling. We also provide a maximum likelihood approach for longitudinal or repeated measures studies where the binary outcome and exposure are assessed on multiple occasions and within-subject pooling is conducted for exposure assessment. Simulation studies illustrate the performance of the proposed approaches along with their computational feasibility using widely available software. We apply the methods to investigate gene–disease association in a population-based case-control study of colorectal cancer.

Lyles, Robert H.; Tang, Li; Lin, Ji; Zhang, Zhiwei; Mukherjee, Bhramar

2012-01-01

71

Petri Net analysis of the MASCOT Pool IDA Communication Mechanisms  

Microsoft Academic Search

The paper is concerned with modelling and analysis of the MASCOT Pool IDA com- munication mechanisms. Both the Four-slot fully asynchronous mechanism and the Two-slot conditionally asynchronous mechanism are investigated. The mechanism properties are defined first, to provide the basis for Petri nets modelling. Place\\/Transition n ets and Coloured Petri nets are used to produce the models. The Design\\/CPN software

Mustafa A. Jiffry

72

New England salt marsh pools: A quantitative analysis of geomorphic and geographic features  

USGS Publications Warehouse

New England salt marsh pools provide important wildlife habitat and are the object of on-going salt marsh restoration projects; however, they have not been quantified in terms of their basic geomorphic and geographic traits. An examination of 32 ditched and unditched salt marshes from the Connecticut shore of Long Island Sound to southern Maine, USA, revealed that pools from ditched and unditched marshes had similar average sizes of about 200 m2, averaged 29 cm in depth, and were located about 11 m from the nearest tidal flow. Unditched marshes had 3 times the density (13 pools/ha), 2.5 times the pool coverage (83 m pool/km transect), and 4 times the total pool surface area per hectare (913 m2 pool/ha salt marsh) of ditched sites. Linear regression analysis demonstrated that an increasing density of ditches (m ditch/ha salt marsh) was negatively correlated with pool density and total pool surface area per hectare. Creek density was positively correlated with these variables. Thus, it was not the mere presence of drainage channels that were associated with low numbers of pools, but their type (ditch versus creek) and abundance. Tidal range was not correlated with pool density or total pool surface area, while marsh latitude had only a weak relationship to total pool surface area per hectare. Pools should be incorporated into salt marsh restoration planning, and the parameters quantified here may be used as initial design targets.

Adamowicz, S.C.; Roman, C.T.

2005-01-01

73

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis  

PubMed Central

Background The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. Methods A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. Results Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer’s disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer’s disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. Conclusions This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.

2013-01-01

74

Post-diagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project  

PubMed Central

Background Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. Methods We conducted an investigation of post-diagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990-2006 with AJCC Stage I-III breast tumors from three prospective U.S. cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years post-diagnosis) using a food frequency questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. Results After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (?0.36 g/day of alcohol, ?0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with non-drinking, regular alcohol intake (?6.0 g/day) was not associated with risk of recurrence (HR for 6-<12 g/day=1.03; 95% CI: 0.86, 1.24; HR for 12-<24 g/day=1.12; 95% CI: 0.93, 1.34; HR for ?24 g/day=1.04; 95% CI: 0.84, 1.31). However, risk varied significantly by menopausal status (p for interaction<0.05). Postmenopausal women who regularly consumed alcohol (?6.0 g/day) had increased risk of recurrence (HR=1.19; 95% CI: 1.01, 1.40). Alcohol intake was not associated with mortality. Conclusions Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. Impact The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis.

Kwan, Marilyn L.; Chen, Wendy Y.; Flatt, Shirley W.; Weltzien, Erin K.; Nechuta, Sarah J.; Poole, Elizabeth M.; Holmes, Michelle D.; Patterson, Ruth E.; Shu, Xiao Ou; Pierce, John P.; Caan, Bette J.

2012-01-01

75

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies  

PubMed Central

Background For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.

2012-01-01

76

Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization rates  

Microsoft Academic Search

Array based DNA pooling techniques facilitate genome-wide scale genotyping of large samples. We describe a structured analysis method for pooled data using internal replication information in large scale genotyping sets. The method takes advantage of information from single nucleotide polymorphisms (SNPs) typed in parallel on a high density array to construct a test statistic with desir- able statistical properties. We

Stuart Macgregor; Peter M. Visscher; Grant Montgomery

2006-01-01

77

Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.  

PubMed Central

OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events.

Hemminki, E.; McPherson, K.

1997-01-01

78

The Role of Prostatitis in Prostate Cancer: Meta-Analysis  

PubMed Central

Objective Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. Evidence Acquisition Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. Selection criteria: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. Evidence Synthesis In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990’s: OR=1.58, 95% CI: 1.35-1.84; 2000’s: OR=1.59, 95% CI: 1.40-1.79; 2010’s: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990’s: OR=1.98, 95% CI: 1.08-3.62; 2000’s: OR=1.64, 95% CI: 1.23-2.19; 2010’s: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90.CONCLUSIONS: the present meta-analysis provides the statistical evidence that the association between prostatitis and prostate cancer is significant.

Yunxia, Zhang; Zhu, Hong; Liu, Junjiang; Pumill, Chris

2013-01-01

79

Microbiological Analysis in Three Diverse Natural Geothermal Bathing Pools in Iceland  

PubMed Central

Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000–40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria.

Thorolfsdottir, Berglind Osk Th.; Marteinsson, Viggo Thor

2013-01-01

80

Calculation Notes for Subsurface Leak Resulting in Pool, TWRS FSAR Accident Analysis  

SciTech Connect

This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Subsurface Leaks Resulting in Pool.

Hall, B.W.

1996-09-25

81

Calculation notes for surface leak resulting in pool, TWRS FSAR accident analysis  

SciTech Connect

This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Surface Leaks Resulting in Pool.

Hall, B.W.

1996-09-25

82

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.  

PubMed

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal. PMID:24695224

Gad, Helge; Koolmeister, Tobias; Jemth, Ann-Sofie; Eshtad, Saeed; Jacques, Sylvain A; Ström, Cecilia E; Svensson, Linda M; Schultz, Niklas; Lundbäck, Thomas; Einarsdottir, Berglind Osk; Saleh, Aljona; Göktürk, Camilla; Baranczewski, Pawel; Svensson, Richard; Berntsson, Ronnie P-A; Gustafsson, Robert; Strömberg, Kia; Sanjiv, Kumar; Jacques-Cordonnier, Marie-Caroline; Desroses, Matthieu; Gustavsson, Anna-Lena; Olofsson, Roger; Johansson, Fredrik; Homan, Evert J; Loseva, Olga; Bräutigam, Lars; Johansson, Lars; Höglund, Andreas; Hagenkort, Anna; Pham, Therese; Altun, Mikael; Gaugaz, Fabienne Z; Vikingsson, Svante; Evers, Bastiaan; Henriksson, Martin; Vallin, Karl S A; Wallner, Olov A; Hammarström, Lars G J; Wiita, Elisee; Almlöf, Ingrid; Kalderén, Christina; Axelsson, Hanna; Djureinovic, Tatjana; Puigvert, Jordi Carreras; Häggblad, Maria; Jeppsson, Fredrik; Martens, Ulf; Lundin, Cecilia; Lundgren, Bo; Granelli, Ingrid; Jensen, Annika Jenmalm; Artursson, Per; Nilsson, Jonas A; Stenmark, Pål; Scobie, Martin; Berglund, Ulrika Warpman; Helleday, Thomas

2014-04-10

83

IGF-I and mammographic density in four geographic locations: a pooled analysis.  

PubMed

Insulin-like growth factor (IGF-I) and prolactin have been found to be associated with breast cancer risk and with mammographic density. In a pooled analysis from 4 geographic locations, we investigated the association of percent mammographic density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set included 1,327 pre- and postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum samples were assayed for IGF-I, IGFBP-3 and prolactin levels using ELISA assays. Mammographic density was quantified using a computer-assisted density method. After stratification by menopausal status, multiple regression models estimated the relation between serum analytes and breast density. All serum analytes except prolactin among postmenopausal women differed significantly by location/ethnicity group. Among premenopausal subjects, IGF-I levels and the molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona. For IGFBP-3, the order was reversed. Among postmenopausal subjects, Norwegian women had the highest IGF-I levels and women in Arizona had the lowest while women in Japan and Hawaii had intermediate levels. We observed no significant relation between percent density and IGF-I or prolactin levels among pre-and postmenopausal women. The significant differences in IGF-I levels by location but not ethnicity suggest that environmental factors influence IGF-I levels, whereas percent breast density varies more according to ethnic background than by location. Based on this analysis, the influence of circulating levels of IGF-I, IGFBP-3, and prolactin on percent density appears to be very small. PMID:17520679

Maskarinec, Gertraud; Takata, Yumie; Chen, Zhao; Gram, Inger Torhild; Nagata, Chisato; Pagano, Ian; Hayashi, Kentaro; Arendell, Leslie; Skeie, Guri; Rinaldi, Sabina; Kaaks, Rudolph

2007-10-15

84

Theoretical Analysis for Corium Pool with Miscibility Gap  

SciTech Connect

A model is proposed describing the corium pool behavior with a material composition presenting a miscibility gap. The model is described in the first part of this paper, and the state of its validation is developed in the second part, against SIMECO experiments. Qualitatively the model predicts the experimental behavior (domain of existence of two layers, phase separation in the boundary layers, and power split). Applicability to the reactor situation is discussed. It is also concluded that the time delay to obtain physicochemical equilibrium between liquid phases is of the same order of magnitude as the time delay necessary to obtain thermal-hydraulic steady state (established heat flux distribution)

Seiler, Jean-Marie; Fouquet, Angelique; Froment, Karine; Defoort, Francoise [Commissariat a l'Energie Atomique, Grenoble (France)

2003-03-15

85

Pre-diagnosis Body Mass Index and Survival After Breast Cancer in the After Breast Cancer Pooling Project  

PubMed Central

Obese and underweight women who develop breast cancer may have poorer survival compared to normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990-2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30-<35 kg/m2), severely obese (35-<40 kg/m2), and morbidly obese (?40 kg/m2) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR=1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR=1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared to normal-weight (18.5-24.9 kg/m2) women. Severe obesity (HR=1.09; 95% CI: 0.88, 1.36) and obesity (HR=1.11; 95% CI: 0.97, 1.27) were related to small, non-significant increased risks. Overweight (25.0-29.9 kg/m2) was not associated with any excess risk compared to normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival.

Kwan, Marilyn L.; Chen, Wendy Y.; Kroenke, Candyce H.; Weltzien, Erin K.; Beasley, Jeannette M.; Nechuta, Sarah J.; Poole, Elizabeth M.; Lu, Wei; Holmes, Michelle D.; Quesenberry, Charles P.; Pierce, John P.; Shu, Xiao Ou; Caan, Bette J.

2012-01-01

86

Pooled analysis of data from multiple quantitative trait locus mapping populations.  

PubMed

Quantitative trait locus (QTL) analysis on pooled data from multiple populations (pooled analysis) provides a means for evaluating, as a whole, evidence for existence of a QTL from different studies and examining differences in gene effect of a QTL among different populations. Objectives of this study were to: (1) develop a method for pooled analysis and (2) conduct pooled analysis on data from two soybean mapping populations. Least square interval mapping was extended for pooled analysis by inclusion of populations and cofactor markers as indicator variables and covariate variables separately in the multiple linear models. The general linear test approach was applied for detecting a QTL. Single population-based and pooled analyses were conducted on data from two F(2:3) mapping populations, Hamilton (susceptible) x PI 90763 (resistant) and Magellan (susceptible) x PI 404198A (resistant), for resistance to soybean cyst nematode (SCN) in soybean. It was demonstrated that where a QTL was shared among populations, pooled analysis showed increased LOD values on the QTL candidate region over single population analyses. Where a QTL was not shared among populations, however, the pooled analysis showed decreased LOD values on the QTL candidate region over single population analyses. Pooled analysis on data from genetically similar populations may have higher power of QTL detection than single population-based analyses. QTLs were identified by pooled analysis on linkage groups (LGs) G, B1 and J for resistance to SCN race 2 whereas QTLs on LGs G, B1 and E for resistance to SCN race 5 in soybean PI 90763 and PI 404198A. QTLs on LG G and B1 were identified in both PI 90763 and PI 404198A whereas QTLs on LG E and J were identified in PI 90763 only. QTLs on LGs G and B1 for resistance to race 2 may be the same or closely linked with QTLs on LG G and B1 for resistance to race 5, respectively. It was further demonstrated that QTLs on G and B1 carried by PI 90763 were not significantly different in gene effect from QTLs on LGs G and B1 in PI 404198A, respectively. PMID:16783590

Guo, B; Sleper, D A; Sun, J; Nguyen, H T; Arelli, P R; Shannon, J G

2006-06-01

87

76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment  

Federal Register 2010, 2011, 2012, 2013

...competition. The attached Analysis to Aid Public Comment...days. The following Analysis to Aid Public Comment...inventories, formulas, patterns, devices, manufacturing...ftc/privacy.htm. Analysis of Agreement Containing...The Agreement is for settlement purposes only and...

2011-11-28

88

Unsuspected pulmonary embolism in cancer patients: a narrative review with pooled data.  

PubMed

Detection of pulmonary embolism (PE) is not uncommon in patients undergoing computed tomography (CT) for routine staging of malignancy. Several studies have been conducted in recent years to evaluate the impact of unsuspected pulmonary embolism (UPE) on the prognosis and management of cancer patients. We aimed at summarizing the available evidence, to improve the understanding of the frequency and clinical significance of UPE in terms of survival, recurrent venous thromboembolism (VTE) and major bleeding. Medline was searched up to the end of September 2013, by using the terms "unsuspected pulmonary embolism" OR "incidental pulmonary embolism" OR "asymptomatic pulmonary embolism". We found 552 out of 35,990 cancer patients diagnosed with UPE (14 studies), for a mean weighted prevalence of 1.82 % (95 % CI 1.47-2.21). When comparing cancer patients diagnosed with UPE to those presenting with symptomatic PE, we found a pooled OR of 0.96 (95 % CI 0.58-1.57) for mortality (3 studies), 0.87 (95 % CI 0.47-1.60) for recurrent VTE (4 studies) and 0.90 (95 % CI 0.43-1.88) for major bleeding (4 studies). In conclusion, UPE represents a non-infrequent finding on CT scans ordered for reasons other than suspected PE and is a challenging clinical situation in the management of cancer patients. Even if UPE is generally milder in the short term, it may share a similar impact on survival and recurrent VTE, as compared to symptomatic PE. Large collaborative projects and, hopefully, interventional trials are needed to clarify the best management strategies. PMID:24664519

Donadini, Marco Paolo; Dentali, Francesco; Squizzato, Alessandro; Guasti, Luigina; Ageno, Walter

2014-06-01

89

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.  

PubMed

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou

2010-07-01

90

RELAP5 Analysis of the Hybrid Loop-Pool Design for Sodium Cooled Fast Reactors  

SciTech Connect

An innovative hybrid loop-pool design for sodium cooled fast reactors (SFR-Hybrid) has been recently proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to improve economics and safety of SFRs. In the hybrid loop-pool design, primary loops are formed by connecting the reactor outlet plenum (hot pool), intermediate heat exchangers (IHX), primary pumps and the reactor inlet plenum with pipes. The primary loops are immersed in the cold pool (buffer pool). Passive safety systems -- modular Pool Reactor Auxiliary Cooling Systems (PRACS) – are added to transfer decay heat from the primary system to the buffer pool during loss of forced circulation (LOFC) transients. The primary systems and the buffer pool are thermally coupled by the PRACS, which is composed of PRACS heat exchangers (PHX), fluidic diodes and connecting pipes. Fluidic diodes are simple, passive devices that provide large flow resistance in one direction and small flow resistance in reverse direction. Direct reactor auxiliary cooling system (DRACS) heat exchangers (DHX) are immersed in the cold pool to transfer decay heat to the environment by natural circulation. To prove the design concepts, especially how the passive safety systems behave during transients such as LOFC with scram, a RELAP5-3D model for the hybrid loop-pool design was developed. The simulations were done for both steady-state and transient conditions. This paper presents the details of RELAP5-3D analysis as well as the calculated thermal response during LOFC with scram. The 250 MW thermal power conventional pool type design of GNEP’s Advanced Burner Test Reactor (ABTR) developed by Argonne National Laboratory was used as the reference reactor core and primary loop design. The reactor inlet temperature is 355 °C and the outlet temperature is 510 °C. The core design is the same as that for ABTR. The steady state buffer pool temperature is the same as the reactor inlet temperature. The peak cladding, hot pool, cold pool and reactor inlet temperatures were calculated during LOFC. The results indicate that there are two phases during LOFC transient – the initial thermal equilibration phase and the long term decay heat removal phase. The initial thermal equilibration phase occurs over a few hundred seconds, as the system adjusts from forced circulation to natural circulation flow. Subsequently, during long-term heat removal phase all temperatures evolve very slowly due to the large thermal inertia of the primary and buffer pool systems. The results clearly show that passive safety PRACS can effectively transfer decay heat from the primary system to the buffer pool by natural circulation. The DRACS system in turn can effectively transfer the decay heat to the environment.

Hongbin Zhang; Haihua Zhao; Cliff Davis

2008-06-01

91

Comprehensive analysis of correlation coefficients estimated from pooling heterogeneous microarray data  

PubMed Central

Background The synthesis of information across microarray studies has been performed by combining statistical results of individual studies (as in a mosaic), or by combining data from multiple studies into a large pool to be analyzed as a single data set (as in a melting pot of data). Specific issues relating to data heterogeneity across microarray studies, such as differences within and between labs or differences among experimental conditions, could lead to equivocal results in a melting pot approach. Results We applied statistical theory to determine the specific effect of different means and heteroskedasticity across 19 groups of microarray data on the sign and magnitude of gene-to-gene Pearson correlation coefficients obtained from the pool of 19 groups. We quantified the biases of the pooled coefficients and compared them to the biases of correlations estimated by an effect-size model. Mean differences across the 19 groups were the main factor determining the magnitude and sign of the pooled coefficients, which showed largest values of bias as they approached ±1. Only heteroskedasticity across the pool of 19 groups resulted in less efficient estimations of correlations than did a classical meta-analysis approach of combining correlation coefficients. These results were corroborated by simulation studies involving either mean differences or heteroskedasticity across a pool of N?>?2 groups. Conclusions The combination of statistical results is best suited for synthesizing the correlation between expression profiles of a gene pair across several microarray studies.

2013-01-01

92

Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis  

SciTech Connect

Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Eppinga, Wietse; Lagerwaard, Frank [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands)] [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Cloughesy, Timothy [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Slotman, Benjamin [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands)] [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Nghiemphu, Phioanh L. [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Selch, Michael T.; Steinberg, Michael [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Kang, Jung Julie [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

2013-07-15

93

PoPoolation: A Toolbox for Population Genetic Analysis of Next Generation Sequencing Data from Pooled Individuals  

Microsoft Academic Search

Recent statistical analyses suggest that sequencing of pooled samples provides a cost effective approach to determine genome-wide population genetic parameters. Here we introduce PoPoolation, a toolbox specifically designed for the population genetic analysis of sequence data from pooled individuals. PoPoolation calculates estimates of ?Watterson, ??, and Tajima's D that account for the bias introduced by pooling and sequencing errors, as

Robert Kofler; Pablo Orozco-Terwengel; Nicola de Maio; Ram Vinay Pandey; Viola Nolte; Andreas Futschik; Carolin Kosiol; Christian Schlötterer; Manfred Kayser

2011-01-01

94

Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies  

PubMed Central

Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.

2013-01-01

95

Nighttime Exposure to Electromagnetic Fields and Childhood Leukemia: An Extended Pooled Analysis  

Microsoft Academic Search

It has been hypothesized that nighttime bedroom measurements of extremely low frequency electromagnetic fields (ELF EMF) may represent a more accurate reflection of exposure and have greater biologic relevance than previously used 24-\\/48-hour measurements. Accordingly, the authors extended a pooled analysis of case-control studies on ELF EMF exposure and risk of childhood leukemia to examine nighttime residential exposures. Data from

Joachim Schuz; Anne Louise Svendsen; Martha S. Linet; Mary L. McBride; Eve Roman; Maria Feychting; Leeka Kheifets; Tracy Lightfoot; Gabor Mezei; Jill Simpson; Anders Ahlbom

2007-01-01

96

Pooled analysis of recent studies on magnetic fields and childhood leukaemia  

PubMed Central

Background: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. Methods: Seven studies with a total of 10?865 cases and 12?853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. Results: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1–0.2??T, 0.2–0.3??T and ?0.3??T, compared with <0.1??T, were 1.07 (95% CI 0.81–1.41), 1.16 (0.69–1.93) and 1.44 (0.88–2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. Conclusions: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.

Kheifets, L; Ahlbom, A; Crespi, C M; Draper, G; Hagihara, J; Lowenthal, R M; Mezei, G; Oksuzyan, S; Schuz, J; Swanson, J; Tittarelli, A; Vinceti, M; Wunsch Filho, V

2010-01-01

97

Remaining Lifetime Risk for Cancer Death at Selected Ages by Sex and Smoking status: The Lifetime Risk Pooling Project  

PubMed Central

Background Understanding how sex and tobacco exposure may modify lifetime risks for cancer mortality is important for effective communication of risk in targeted public health messages. Objective To determine lifetime risk estimates for cancer death associated with sex and smoking status in the United States. Methods A pooled cohort design using ten well-defined epidemiologic cohorts including middle-aged and older individuals was used to estimate the lifetime risk for cancer death at selected index ages, with death from non-cancer causes as the competing risk, by sex and smoking status. Results There were a total of 11,317 cancer-related deaths. At age 45 years, the lifetime risk of cancer death for male smokers is 27.7% (95% CI 24.0% to 31.4%) compared to 15.8% (95% CI 12.7% to 18.9%) for male non-smokers. At age 45 years, the lifetime risk of cancer death for female smokers is 21.7% (95% CI 18.8% to 24.6%) compared to 13.2% (95% CI 11.0% to 15.4%) for female non-smokers. Remaining lifetime risk for cancer death declined with age, and men have a greater risk for cancer death compared to women. Adjustment for competing risk of death, particularly representing cardiovascular mortality, yielded a greater change in lifetime risk estimates for men and smokers compared to women and non-smokers. Conclusions At the population level the lifetime risk for cancer death remains significantly higher for smokers compared to non-smokers, regardless of sex. These estimates may provide clinicians with useful information for counseling individual patients and highlight the need for continued public health efforts related to smoking cessation.

Gawron, Andrew; Hou, Lifang; Ning, Hongyan; Berry, Jarett D.; Lloyd-Jones, Donald M.

2012-01-01

98

One-Dimensional Analysis of Thermal Stratification in AHTR and SFR Coolant Pools  

SciTech Connect

Thermal stratification phenomena are very common in pool type reactor systems, such as the liquid-salt cooled Advanced High Temperature Reactor (AHTR) and liquid-metal cooled fast reactor systems such as the Sodium Fast Reactor (SFR). It is important to accurately predict the temperature and density distributions both for design optimation and accident analysis. Current major reactor system analysis codes such as RELAP5 (for LWR’s, and recently extended to analyze high temperature reactors), TRAC (for LWR’s), and SASSYS (for liquid metal fast reactors) only provide lumped-volume based models which can only give very approximate results and can only handle simple cases with one mixing source. While 2-D or 3-D CFD methods can be used to analyze simple configurations, these methods require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, yet such fine grid resolution is difficult or impossible to provide for studying the reactor response to transients due to computational expense. Therefore, new methods are needed to support design optimization and safety analysis of Generation IV pool type reactor systems. Previous scaling has shown that stratified mixing processes in large stably stratified enclosures can be described using one-dimensional differential equations, with the vertical transport by free and wall jets modeled using standard integral techniques. This allows very large reductions in computational effort compared to three-dimensional numerical modeling of turbulent mixing in large enclosures. The BMIX++ (Berkeley mechanistic MIXing code in C++) code was originally developed at UC Berkeley to implement such ideas. This code solves mixing and heat transfer problems in stably stratified enclosures. The code uses a Lagrangian approach to solve 1-D transient governing equations for the ambient fluid and uses analytical or 1-D integral models to compute substructures. By including liquid salt properties, BMIX++ code is extended to analyze liquid salt pool systems in the current AHTR design, to provide an example of its application. Similar analysis is possible for liquid-metal cooled reactors. The current AHTR baseline design uses a large buffer salt tank to provide more thermal inertial and safety margin. Reactor vessel, intermediate heat exchangers, pool reactor auxiliary cooling system heat exchangers (PHX), and direct reactor auxiliary cooling system heat exchangers (DHX) are all immerged in the buffer salt pool. These structures provide major driving sources for vertical mixing and thermal stratification. Predication of the temperature distribution within the buffer salt tank directly affects the major safety systems design, such as the PHX and DHX, safety analysis results, and structure thermal stresses analysis. The BMIX++ code is used to predict mixing and thermal stratification in this pool system. This example shows the potential of 1-D analysis methods and BMIX++ to be included in system analysis codes for pool type of Gen-IV reactor systems.

Haihua Zhao; Per F. Peterson

2007-10-01

99

Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies  

PubMed Central

Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1?mg/kg body weight) or buspirone (5?mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization.

Bellavite, Paolo; Conforti, Anita; Marzotto, Marta; Magnani, Paolo; Cristofoletti, Mirko; Olioso, Debora; Zanolin, Maria Elisabetta

2012-01-01

100

Fourier analysis of a gated blood-pool study during atrial flutter  

SciTech Connect

First-harmonic Fourier analysis of a gated blood-pool study is based on the assumption that the cardiac chambers contract once per cardiac cycle. In atrial arrhythmias this condition may not exist for the atria. We recently studied a patient with atrial flutter and 2:1 artioventricular conduction. There were predictable alterations in the first-harmonic Fourier phase and amplitude images. The observed changes from first-harmonic Fourier analysis were: (a) very low atrial amplitude values, and (b) absence of identifiable atrial regions on the phase image.

Makler, P.T. Jr.; McCarthy, D.M.; London, J.W.; Sandler, M.S.; Alavi, A.

1983-08-01

101

Swimming Pools.  

ERIC Educational Resources Information Center

Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

Ministry of Housing and Local Government, London (England).

102

Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC Review  

PubMed Central

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

Taioli, E.; Garza, M. A.; Ahn, Y. O.; Bishop, D. T.; Bost, J.; Budai, B.; Chen, K.; Gemignani, F.; Keku, T.; Lima, C. S. P.; Le Marchand, L.; Matsuo, K.; Moreno, V.; Plaschke, J.; Pufulete, M.; Thomas, S. B.; Toffoli, G.; Wolf, C. R.; Moore, C. G.; Little, J.

2009-01-01

103

SNP genotyping on pooled DNAs: comparison of genotyping technologies and a semi automated method for data storage and analysis  

PubMed Central

We have compared the accuracy, efficiency and robustness of three methods of genotyping single nucleotide polymorphisms on pooled DNAs. We conclude that (i) the frequencies of the two alleles in pools should be corrected with a factor for unequal allelic amplification, which should be estimated from the mean ratio of a set of heterozygotes (k); (ii) the repeatability of an assay is more important than pinpoint accuracy when estimating allele frequencies, and assays should therefore be optimised to increase the repeatability; and (iii) the size of a pool has a relatively small effect on the accuracy of allele frequency estimation. We therefore recommend that large pools are genotyped and replicated a minimum of four times. In addition, we describe statistical approaches to allow rigorous comparison of DNA pool results. Finally, we describe an extension to our ACeDB database that facilitates management and analysis of the data generated by association studies.

Le Hellard, Stephanie; Ballereau, Stephane J.; Visscher, Peter M.; Torrance, Helen S.; Pinson, Jeni; Morris, Stewart W.; Thomson, Marian L.; Semple, Colin A. M.; Muir, Walter J.; Blackwood, Douglas H. R.; Porteous, David J.; Evans, Kathryn L.

2002-01-01

104

Milk Consumption and Bladder Cancer Risk: A Meta-Analysis of Published Epidemiological Studies  

Microsoft Academic Search

Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of

Qi-Qi Mao; Yun Dai; Yi-Wei Lin; Jie Qin; Li-Ping Xie; Xiang-Yi Zheng

2011-01-01

105

Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool ("metabolome") analysis.  

PubMed

Escherichia coli growing on glucose in minimal medium controls its metabolite pools in response to environmental conditions. The extent of pool changes was followed through two-dimensional thin-layer chromatography of all 14C-glucose labelled compounds extracted from bacteria. The patterns of metabolites and spot intensities detected by phosphorimaging were found to reproducibly differ depending on culture conditions. Clear trends were apparent in the pool sizes of several of the 70 most abundant metabolites extracted from bacteria growing in glucose-limited chemostats at different growth rates. The pools of glutamate, aspartate, trehalose, and adenosine as well as UDP-sugars and putrescine changed markedly. The data on pools observed by two-dimensional thin-layer chromatography were confirmed for amino acids by independent analysis. Other unidentified metabolites also displayed different spot intensities under various conditions, with four trend patterns depending on growth rate. As RpoS controls a number of metabolic genes in response to nutrient limitation, an rpoS mutant was also analyzed for metabolite pools. The mutant had altered metabolite profiles, but only some of the changes at slow growth rates were ascribable to the known control of metabolic genes by RpoS. These results indicate that total metabolite pool ("metabolome") analysis offers a means of revealing novel aspects of cellular metabolism and global regulation. PMID:9748443

Tweeddale, H; Notley-McRobb, L; Ferenci, T

1998-10-01

106

A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses following Colonoscopic Polypectomy  

PubMed Central

Background & Aims Limited data exist regarding the actual risk of developing advanced adenomas and cancer following polypectomy or the factors that determine risk. Methods We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously-resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with development of advanced colorectal neoplasms during surveillance. Results During a median follow-up of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; SE=2.2) and those with an adenoma 20 mm in size or greater (19.3%; SE=1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P <0.0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI] 1.19–1.65) were significantly associated with increased risk of metachronous advanced neoplasia, as were the number and size of prior adenomas (P <0.0001 for trend), the presence of villous features (OR, 1.28; 95% CI 1.07–1.52), and proximal location (OR, 1.68; 95% CI 1.43–1.98). High-grade dysplasia was not independently associated with metachronous advanced neoplasia after adjustment for other adenoma characteristics. Conclusions Occurrence of advanced colorectal neoplasia is common following polypectomy. Factors that are most strongly associated with risk of advanced neoplasia are patient age and the number and size of prior adenomas.

Martinez, Maria Elena; Baron, John A.; Lieberman, David A.; Schatzkin, Arthur; Lanza, Elaine; Winawer, Sidney J.; Zauber, Ann G.; Jiang, Ruiyun; Ahnen, Dennis J.; Bond, John H.; Church, Timothy R.; Robertson, Douglas J.; Smith-Warner, Stephanie A.; Jacobs, Elizabeth T.; Alberts, David S.; Greenberg, E. Robert

2013-01-01

107

Melt pool and keyhole behaviour analysis for deep penetration laser welding  

NASA Astrophysics Data System (ADS)

One usually defines the main characteristic of the welding performances of a given laser system by its 'penetration curve' that corresponds to the welding depth as a function of the welding speed Vw for a given set of operating parameters. Analysis of a penetration curve is interesting and gives very fruitful results. Coupled with high-speed video imaging of melt pool surface and ejected plume behaviour, the analysis of this penetration curve on a very large range of welding speeds, typically from 0 to 50 m min-1, has allowed us to observe very different and characteristic regimes. These regimes are mainly characterized by the physical processes by which they impede the laser beam penetration inside the material. We show that it is only at rather high welding speeds that these limiting processes are reduced. Consequently, the scaling law of welding depth with welding speed is in agreement with adapted modelling of this process. On the other hand, as the welding speed is reduced, different effects depending on the weld pool dynamics and plume interaction strongly disturb the keyhole stability and are responsible for the deviation of the penetration curve from the previous modelling that agrees with a 1/Vw scaling law. A corresponding criterion for the occurrence of this effect is defined.

Fabbro, R.

2010-11-01

108

Methods of Using an Array of Pooled Probes in Genetic Analysis.  

National Technical Information Service (NTIS)

The invention provides arrays of polynucleotide probes having at least one pooled position. A typical array comprises a support having at least three discrete regions. A first region bears a pool of polynucleotide probes comprising first and second probes...

E. Gentalen M. Chee

2005-01-01

109

Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials  

PubMed Central

Background It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs. Methods Pooled analyses were performed of 20 randomized controlled studies (N?=?9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin?+?metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method). Results In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin?+?metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12). Conclusions Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk.

2014-01-01

110

Breast self-examination and death from breast cancer: a meta-analysis.  

PubMed

Breast self-examination (BSE) is widely recommended for breast cancer prevention. Following recent controversy over the efficacy of mammography, it may be seen as an alternative. We present a meta-analysis of the effect of regular BSE on breast cancer mortality. From a search of the medical literature, 20 observational studies and three clinical trials were identified that reported on breast cancer death rates or rates of advanced breast cancer (a marker of death) according to BSE practice. A lower risk of mortality or advanced breast cancer was only found in studies of women with breast cancer who reported practising BSE before diagnosis (mortality: pooled relative risk 0.64, 95% CI 0.56-0.73; advanced cancer, pooled relative risk 0.60, 95% CI 0.46-0.80). The results are probably due to bias and confounding. There was no difference in death rate in studies on women who detected their cancer during an examination (pooled relative risk 0.90, 95% CI 0.72-1.12). None of the trials of BSE training (in which most women reported practising it regularly) showed lower mortality in the BSE group (pooled relative risk 1.01, 95% CI 0.92-1.12). They did show that BSE is associated with considerably more women seeking medical advice and having biopsies. Regular BSE is not an effective method of reducing breast cancer mortality. PMID:12671703

Hackshaw, A K; Paul, E A

2003-04-01

111

DNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters.  

PubMed

ADHD is one of the most prevalent, and heritable behavioural disorders in childhood. Genetic associations have been reported with polymorphic variants within or near to dopamine pathway genes. Recently snap-25 has also shown association with ADHD in several datasets. We therefore investigated other genes that produce proteins that interact with SNAP-25 in the mechanism of vesicular release of neurotransmitters at the synapse. A total of 106 SNPs were screened for minor allele frequency greater than 5% and 61 SNPs selected for analysis in DNA pools made up from an ADHD clinical sample of DSM-IV combined type probands (n = 180) and a control sample of 90 males and 90 females. Initial screening identified several SNPs that showed allele frequency differences of 5% or more. One SNP in the synaptophysin gene showed suggestive evidence of association following case-control and TDT analysis and warrants further investigation. PMID:16082702

Brookes, K J; Knight, J; Xu, X; Asherson, P

2005-11-01

112

PWR core and spent fuel pool analysis using scale and nestle  

SciTech Connect

The SCALE nuclear analysis code system [SCALE, 2011], developed and maintained at Oak Ridge National Laboratory (ORNL) is widely recognized as high quality software for analyzing nuclear systems. The SCALE code system is composed of several validated computer codes and methods with standard control sequences, such as the TRITON/NEWT lattice physics sequence, which supplies dependable and accurate analyses for industry, regulators, and academia. Although TRITON generates energy-collapsed and space-homogenized few group cross sections, SCALE does not include a full-core nodal neutron diffusion simulation module within. However, in the past few years, the open-source NESTLE core simulator [NESTLE, 2003], originally developed at North Carolina State Univ. (NCSU), has been updated and upgraded via collaboration between ORNL and the Univ. of Tennessee (UT), so it now has a growingly seamless coupling to the TRITON/NEWT lattice physics [Galloway, 2010]. This study presents the methodology used to couple lattice physics data between TRITON and NESTLE in order to perform a three-dimensional full-core analysis employing a 'real-life' Duke Energy PWR as the test bed. The focus for this step was to compare the key parameters of core reactivity and radial power distribution versus plant data. Following the core analysis, following a three cycle burn, a spent fuel pool analysis was done using information generated from NESTLE for the discharged bundles and was compared to Duke Energy spent fuel pool models. The KENO control module from SCALE was employed for this latter stage of the project. (authors)

Murphy, J. E.; Maldonado, G. I. [Dept. of Nuclear Engineering, Univ. of Tennessee, Knoxville, TN 37996-2300 (United States); St Clair, R.; Orr, D. [Duke Energy, 526 S. Church St, Charlotte, NC 28202 (United States)

2012-07-01

113

Correlation analysis connects cancer subtypes.  

PubMed

We provided a cross-tissue comparative analysis of between-subtype molecular commonality for ovarian cancer, breast cancer, hepatocellular carcinoma, glioma, lung squamous carcinoma and nasopharyngeal carcinoma. Our analysis showed that molecular subtypes with similar phenotype or similar clinical outcome could be correlated by their transcriptional profile and pathway profile. Pathway dysregulation across multiple cancer subtypes was also revealed by Gene Set Enrichment Analysis. Dysregulation of 'complement and coagulation cascades' was observed in a total of eleven subtypes across five tissues, implicating that the role of this process in personalized immune-based therapy may be worth further exploring. PMID:23861980

Lin, Pei; Huang, Zhongxi

2013-01-01

114

Aspirin use and breast cancer risk: a meta-analysis.  

PubMed

Animal and in vitro studies suggest that the use of aspirin may be associated with reduced risk for breast cancer, but results from these studies of the association have been inconsistent. The objective of this meta-analysis was to quantitatively summarize the current evidence for such a relationship. We searched MEDLINE for studies of aspirin use and breast cancer risk that were published in any language, from January 1, 1966, to July 1, 2011. A total of 33 studies (19 cohort studies, 13 case-control studies, and 1 randomized controlled trial [RCT]) that included 1,916,448 subjects were identified. We pooled the relative risks from individual studies using a random-effects model, heterogeneity, and publication bias analyses. In a pooled analysis of all studies, aspirin use was associated with reduced risk for breast cancer (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.81, 0.92). In the subgroup analysis by study design, results were similar except for RCT (OR = 0.98, 95% CI = 0.87, 1.09). In conclusion, this meta-analysis indicated that regular use of aspirin may be associated with reduced risk of breast cancer. More RCT were needed to confirm this association in the future. PMID:21898115

Luo, Ting; Yan, Hua-Mei; He, Ping; Luo, Yong; Yang, Yuan-Fu; Zheng, Hong

2012-01-01

115

Equilibrium analysis of carbon pools and fluxes of forest biomes in the former Soviet Union  

SciTech Connect

Forests are an important component of the biosphere and sequestration of carbon in boreal forests may represent one of the few realistic alternatives to ameliorate changes in atmospheric chemistry. The former Soviet Union has the greatest expanse of boreal forests in the world; however, the role of these forests in the terrestrial carbon cycle is not fully understood because the carbon budget of the Soviet forest sector has not been established. In recognition of the need to determine the role of these forests in the global carbon cycle, the carbon budget of forest biomes in the former Soviet Union was assessed based on an equilibrium analysis of carbon cycle pools and fluxes. Net primary productivity was used to identify the rate of carbon turnover in the forest biomes.

Kolchugina, T.P.; Vinson, T.S.

1993-01-01

116

Individual data pooled analyses to improve understanding of adjuvant therapy in colon cancer: Review of the ACCENT collaborative group  

Microsoft Academic Search

The Adjuvant Colon Cancer Endpoints (ACCENT) Group is an international, collaborative, individual-patient data analysis now\\u000a including 20,898 patients enrolled in 18 adjuvant therapy trials for resected stage II and stage III colon cancer, spanning\\u000a the years 1977 to 1999. This article discusses the proceedings published and presented since the inception of the ACCENT Group\\u000a in 2003, which notably include the

Sharlene Gill; Daniel J. Sargent

2008-01-01

117

Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers  

PubMed Central

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations.

Gallicchio, Lisa; Helzlsouer, Kathy J.; Chow, Wong-Ho; Freedman, D. Michal; Hankinson, Susan E.; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B.; Horst, Ronald L.; Koenig, Karen L.; Kolonel, Laurence N.; Laden, Francine; McCullough, Marjorie L.; Parisi, Dominick; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Stolzenberg-Solomon, Rachael Z.; Tworoger, Shelley S.; Varanasi, Arti; Virtamo, Jarmo; Wilkens, Lynne R.; Xiang, Yong-Bing; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Abnet, Christian C.; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J.

2010-01-01

118

Analysis and improvement of data-set level file distribution in Disk Pool Manager  

NASA Astrophysics Data System (ADS)

Of the three most widely used implementations of the WLCG Storage Element specification, Disk Pool Manager[1, 2] (DPM) has the simplest implementation of file placement balancing (StoRM doesn't attempt this, leaving it up to the underlying filesystem, which can be very sophisticated in itself). DPM uses a round-robin algorithm (with optional filesystem weighting), for placing files across filesystems and servers. This does a reasonable job of evenly distributing files across the storage array provided to it. However, it does not offer any guarantees of the evenness of distribution of that subset of files associated with a given "dataset" (which often maps onto a "directory" in the DPM namespace (DPNS)). It is useful to consider a concept of "balance", where an optimally balanced set of files indicates that the files are distributed evenly across all of the pool nodes. The best case performance of the round robin algorithm is to maintain balance, it has no mechanism to improve balance. In the past year or more, larger DPM sites have noticed load spikes on individual disk servers, and suspected that these were exacerbated by excesses of files from popular datasets on those servers. We present here a software tool which analyses file distribution for all datasets in a DPM SE, providing a measure of the poorness of file location in this context. Further, the tool provides a list of file movement actions which will improve dataset-level file distribution, and can action those file movements itself. We present results of such an analysis on the UKI-SCOTGRID-GLASGOW Production DPM.

Cadellin Skipsey, Samuel; Purdie, Stuart; Britton, David; Mitchell, Mark; Bhimji, Wahid; Smith, David

2014-06-01

119

Multidrug-resistant MCF7 breast cancer cells contain deficient intracellular calcium pools  

Microsoft Academic Search

Emergence of resistance to antineoplastic drugs poses a major impediment to the successful treatment of breast cancer. We previously reported that human breast carcinoma MCF-7 cells selected for resistance against doxoru-bicin (MCF-7\\/DOX cells) expressed high levels of tissue-type transglutaminase (tTGase), a calcium-dependent protein cross-linking enzyme that plays a role in apoptosis. The purpose of this study was to determine the

Jack S. K. Chen; Neeraj Agarwal; Kapil Mehta

2002-01-01

120

Analysis of the transport phenomena in the interfacial region between TIG arcs and weld pools  

Microsoft Academic Search

It is of considerable practical interest in welding to provide a faithful representation of dynamic coupling between the welding arc and the weld pool surface. This paper introduces a three-dimensional model for fluid flow and heat transfer in the interfacial region between the TIG arc plasma and weld pool. It accounts for the interaction between the arc plasma and the

Z. Y. Li; C. S. Wu

1997-01-01

121

Analysis of indoor environmental conditions and heat pump energy supply systems in indoor swimming pools  

Microsoft Academic Search

For indoor swimming pools, a lot of energy is needed to control the indoor temperature, relative humidity and pool water temperature. Meanwhile, the indoor air contains a high specific enthalpy due to water evaporation. A new heat pump dehumidifier is studied to reduce energy consumption. The most significant feature of this system is that it can not only recover the

Peng Sun; Jing Yi Wu; Ru Zhu Wang; Yu Xiong Xu

2011-01-01

122

Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis  

PubMed Central

Background Studies on the association between obesity and ovarian cancer survival have had conflicting results. We reviewed and quantitatively summarized the existing evidence, exploring potentially important sources of variability, such as the timing of body mass index (BMI) assessment, BMI cut points, references used in multivariate analysis, and ovarian cancer stage. Methods Eligible studies were searched using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials, relevant bibliographies were manually reviewed for additional studies. Adjusted hazard ratios (HRs) from individual studies were pooled using a random effects model. Results 17 cohort studies of 929 screened articles were included in the final analysis. Obesity in early adulthood and obesity 5 years before ovarian cancer diagnosis were associated with poor patient survival (early adulthood: pooled HR 1.67; 95% CI 1.29-2.16; 5 years prediagnosis: pooled HR 1.35; 95% CI 1.03-1.76). However, the results for obesity at diagnosis depended on whether BMI was analyzed as a categorical or continuous variable. Analysis of obesity with BMI as a categorical variable did not affect ovarian cancer prognosis (pooled HR 1.07; 95% CI 0.95-1.21); obesity with BMI as a continuous variable showed slightly poorer survival with each incremental increase in BMI (pooled HR 1.02; 95% CI 1.01-1.04). Conclusions Obesity 5 years before ovarian cancer diagnosis and obesity at a young age were associated with poor prognosis. The association between obesity at diagnosis and survival of ovarian cancer patients still remains equivocal. BMI at diagnosis cannot be a prognostic factor for the survival of ovarian cancer patients. Further well-designed studies are needed to elucidate the variety effect of obesity on the survival of ovarian cancer patients.

2014-01-01

123

RAPID ANALYSIS OF CYANURIC ACID IN SWIMMING POOL WATERS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USING POROUS GRAPHITIC CARBON  

EPA Science Inventory

An innovative approach is presented for reducing analysis times of cynuric acid in swimming pool waters by high performance liquid chromatography (HPLC). The HPLC method exploits the unique selectivity of porous graphitic carbon (PGC) to fully resolve within 10 minutes cyanuric ...

124

RAPID ANALYSIS OF CYNANURIC ACID IN SWIMMING POOL WATERS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USING POROUS GRAPHITIC CARBON COLUMN  

EPA Science Inventory

An innovative approach is presented for reducing analysis times of cyanuric acid in swimming pool waters by high performance liquid chromatography (HPLC). The HPLC method exploits the unique selectivity of porous graphitic carbon (PGC) to fully resolve cyanuric acid from other p...

125

Reduced Risk of Cytomegalovirus Infection in Solid Organ Transplant Recipients Treated With Sirolimus: A Pooled Analysis of Clinical Trials  

Microsoft Academic Search

IntroductionCytomegalovirus (CMV) is an opportunistic infection that causes substantial morbidity and mortality in transplant recipients. This pooled analysis of Wyeth clinical trials explored the incidence of CMV infection in solid organ transplant recipients treated with sirolimus versus comparator immunosuppressant drugs.

L. Demopoulos; M. Polinsky; G. Steele; D. Mines; M. Blum; M. Caulfield; A. Adamkovic; Q. Liu; M. B. Harler; C. Hahn; A. Singh

2008-01-01

126

"Pooled analysis of brain activity in Irritable Bowel Syndrome and controls during rectal balloon distension"  

PubMed Central

Background Brain-imaging literature of Irritable Bowel Syndrome (IBS) suggests an abnormal brain-gut communication. We analyzed the literature to evaluate and compare the aspects of brain activity in individuals with IBS and control subjects experiencing controlled rectal stimulation. Methods PubMed was searched until September 2010. Data from 16 articles reporting brain activity during rectal balloon distensions in IBS compared to control groups was analyzed. Prevalence rates and pairwise activations were assessed using binomial distributions for 11 selected regions of interest. The data was aggregated to adjust for center effect. Key Results There was considerable variability in the literature regarding regions and their activity patterns in controls and individuals with IBS. There was no significant difference found in the thalamus, ACC, PCC, and PFC, however results show limited evidence of consensus for the Anterior Insula (AI) (p = 0.22). Pairwise activity results suggest that pairs involving the AI tend to have more consistent activity together than pairs which do not involve the AI (Posterior Insula and AI, p = 0.08; Posterior Cingulate Cortex and AI, p = 0.16), however no pairwise evaluation reached significance. Conclusions & Inferences Our pooled analysis demonstrates that the literature reports are quite heterogeneous but there is some evidence that there may be patterns of higher activity more common in individuals with IBS than in controls. A consensus, though, regarding study designs, analysis approach and reporting could create a clearer understanding of brain involvement in IBS pathophysiology.

Sheehan, James; Gaman, Alexander; Vangel, Mark; Kuo, Braden

2010-01-01

127

The Cancer Genome Atlas completes detailed ovarian cancer analysis:  

Cancer.gov

An analysis of genomic changes in ovarian cancer has provided the most comprehensive and integrated view of cancer genes for any cancer type to date. Ovarian serous adenocarcinoma tumors from 500 patients were examined by The Cancer Genome Atlas (TCGA) Research Network. TCGA researchers completed whole-exome sequencing, which examines the protein-coding regions of the genome, on an unprecedented 316 tumors.

128

Pool Purification  

NASA Technical Reports Server (NTRS)

Caribbean Clear, Inc. used NASA's silver ion technology as a basis for its automatic pool purifier. System offers alternative approach to conventional purification chemicals. Caribbean Clear's principal markets are swimming pool owners who want to eliminate chlorine and bromine. Purifiers in Caribbean Clear System are same silver ions used in Apollo System to kill bacteria, plus copper ions to kill algae. They produce spa or pool water that exceeds EPA Standards for drinking water.

1988-01-01

129

Chapter 14: Cancer Genome Analysis  

PubMed Central

Although there is great promise in the benefits to be obtained by analyzing cancer genomes, numerous challenges hinder different stages of the process, from the problem of sample preparation and the validation of the experimental techniques, to the interpretation of the results. This chapter specifically focuses on the technical issues associated with the bioinformatics analysis of cancer genome data. The main issues addressed are the use of database and software resources, the use of analysis workflows and the presentation of clinically relevant action items. We attempt to aid new developers in the field by describing the different stages of analysis and discussing current approaches, as well as by providing practical advice on how to access and use resources, and how to implement recommendations. Real cases from cancer genome projects are used as examples.

Vazquez, Miguel; de la Torre, Victor; Valencia, Alfonso

2012-01-01

130

Treatment of hepatitis C after kidney transplant: A pooled analysis of observational studies.  

PubMed

Various authors have given IFN-based therapy for hepatitis C among renal transplant recipients but the efficacy and safety of this approach remains unclear. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to assess efficacy and safety of antiviral therapy (IFN-based therapy) in renal transplant recipients with hepatitis C virus infection. The primary outcomes were sustained virological response (as a measure of efficacy) and/or drop-out rate (as a measure of tolerability). The random-effects model of DerSimonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen studies (187 unique patients) were identified, one being controlled study. The summary estimate for sustained virological response and dropout rate was 0.34 (95% confidence intervals: 0.27, 0.42) and 0.32 (95% CI: 0.21, 0.44), respectively. The studies were heterogeneous with regard to dropout rate but not to sustained viral response. The most common side-effect requiring interruption of treatment was graft dysfunction (n?=?27; 51%). Stratified analysis reported a higher rate of drop-outs in those studies based on IFN monotherapy (pooled event rate, 0.43; 95% CI: 0.25, 0.63). Meta-regression analysis showed an inverse relationship between reference year (P?=?0.019), length of IFN therapy (P?=?0.029) and drop-out rate. IFN-based therapy has inadequate safety and tolerance after renal transplantation. The reasons for the high rate of graft dysfunction after IFN have not been fully elucidated. Antiviral treatment of hepatitis C among kidney graft recipients continues to be a challenge to transplant physicians. J. Med. Virol. 86:933-940, 2014. © 2017 Wiley Periodicals, Inc. PMID:24610278

Fabrizi, Fabrizio; Penatti, Alessandra; Messa, Piergiorgio; Martin, Paul

2014-06-01

131

Furazolidone-based Therapies for Helicobacter pylori Infection: A Pooled-data Analysis  

PubMed Central

Background/Aim: Furazolidone-based therapies are used in developing countries to cure Helicobacter pylori infection due to its low cost. The low bacterial resistance toward furazolidone may render appealing the use of this drug even in developed countries. However, some relevant safety concerns do exist in using furazolidone. Patients and Methods: This was a systematic review with pooled-data analysis of data regarding both eradication rate and safety of furazolidone-based therapies for H. pylori infection. Intention-to-treat (ITT) and per-protocol (PP) eradication rates were calculated. Results: Following furazolidone-based first-line therapy, H. pylori eradication rates were 75.7% and 79.6% at ITT and PP analysis, respectively (P<0.001). The overall incidence of side effects and severe side effects were 33.2% and 3.8%, respectively. At multivariate analysis, only high-dose furazolidone was associated with increased therapeutic success (OR: 1.5, 95% CI: 1.3-2.7; P<0.001), while occurrence of side effects was relevant following treatment for a long duration (OR: 2.9, 95% CI: 2.2-4.1; P<0.001), high-dose furazolidone (OR: 2.3, 95% CI: 1.7-3.2; P<0.001) and bismuth-containing regimens (OR: 2.1, 95% CI: 1.5-2.8; P<0.001). Conclusions: Furazolidone-based regimens usually achieve low eradication rates. Only a high-dose regimen improves the cure rate, but simultaneously increases the incidence of severe side effects. Therefore, we suggest that patients have to be clearly informed about the possible genotoxic and carcinogenetic effects for which furazolidone use is not approved in developed countries.

Zullo, Angelo; Ierardi, Enzo; Hassan, Cesare; Francesco, Vincenzo De

2012-01-01

132

[The Dagestan gene pool: analysis of the frequencies of classical genetic markers in Avars].  

PubMed

This study is part of long-term research in the gene pool of Dagestan ethnic groups. The phenotype (in percent), gene, and haplotype frequencies in three Avar populations are reported. A total of 37 alleles of 13 loci of immune and biochemical genetic marker systems (ABO, Rhesus, P, Lewis, HP, GC, C'3, TF, 6PGD, GLO1, ESD, ACP, and PGM1) have been studied. Rare haplotypes of the Rhesus system (CDE, Cde, and cdE) have been found in the populations studied. In two out of three local populations (Khunzakh and Kharakhi), a typically "Caucasoid" rare gene ACP1c of the AcP1 locus has proved to be relatively frequent (0.030 and 0.023, respectively). The frequencies of the allele variants P2, le, and Hp1 of loci of the P, Lewis, and HP systems, respectively, have been found to be lower than in other Caucasian ethnic groups and the total northern Eurasian population. The mean allele frequencies for the GC, C'3, TF, 6PGD, GLO1, and ESD systems in the populations studied are comparable wit those for both Caucasian ethnic groups and the total population of the European historical ethnographic province. Statistical analysis of the results has shown 11 cases of significant deviations of the observed phenotype frequencies from the Hardy-Weinberg equilibrium. PMID:20536025

Radzhabov, M O; Mamaev, I A; Shamov, I A; Gasaev, D G; Shil'nikova, I N; Shne?der, Iu V

2010-04-01

133

Bleeding Risk and Mortality of Edoxaban: A Pooled Meta-Analysis of Randomized Controlled Trials  

PubMed Central

Objective(s) Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored. Methods Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality. Results Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI0.85 to0.99, p?=?0.02] and cardiovascular mortality [RR 0.87, 95% CI0.79 to 0.96, p?=?0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p?=?0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p?=?0.002) respectively in any bleeding; as well as 0.86 (p?=?0.01), 0.87 (p?=?0.01) and 0.28 (p?=?0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p?=?0.02) and any bleeding (p?=?0.002), but neither in all-cause death (p?=?0.66) nor cardiovascular death (p?=?0.70). Conclusions Edoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.

Xu, Dachun; Xu, Yawei

2014-01-01

134

Thermal analysis of five outdoor swimming pools heated by unglazed solar collectors  

SciTech Connect

We have analysed measurement from five outdoor swimming pools located in Switzerland and heated by unglazed solar collectors. The main contributions to the daily energy balance of the swimming pools are evaluated. They include the active and passive solar gains, as well as the heat losses related to radiation, evaporation, convection, and water renewal (in order of importance). Coherent results are obtained using multilinear regressions in order to determine the best fitting values of the empirical parameters involved in the thermal equations.

Molineaux, B.; Lachal, B.; Guisan, O. (Univ. of Geneva (Switzerland))

1994-07-01

135

Analysis of haloacetic acids in water and air (aerosols) from indoor swimming pools using HS-SPME\\/GC\\/ECD  

Microsoft Academic Search

A solid phase microextraction method was used for the analysis of nine haloacetic acids (HAAs) in water and air (aerosols) from indoor swimming pools (ISPs). The analysis is characterized by derivatization of HAAs to their methyl-esters with dimethyl sulphate, headspace solid phase microextraction (HS-SPME) with a Carboxen–polydimethylsiloxane (CAR-PDMS) fiber and gas chromatography - electron capture detector (GC\\/ECD). High correlation coefficients

Christopher S. A. Sá; Rui A. R. Boaventura; Isabel B. Pereira

2012-01-01

136

Radial Scars and Subsequent Breast Cancer Risk: A Meta-Analysis  

PubMed Central

Background The relationship between radial scars and breast cancer is unclear, as the results of different studies are inconsistent. We aim to solve the controversy and assess the breast cancer risk of radial scars. Methods Case-control or cohort studies about radial scars and breast cancer risk published in PubMed, Web of Science and the Cochrane Library from 2000 to 2013 were searched. Heterogeneity for the eligible data was assessed and a pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results Five observational studies involving 2521 cases and 20290 controls were included in our study. From pooled analysis, radial scars were found to have a 1.33 fold increased risk of breast cancer, but which was not significant (P?=?0.138). Sample size contributed to heterogeneity. In subgroup analysis, the results pooled from studies with sample size >2000 show that presence of radial scars was associated with 1.6 times breast cancer risk compared to absence of radial scars. Radial scars increased the risk of breast cancer among women with proliferative disease without atypia, but no significant association between radial scars and carcinoma was noted among women with atypical hyperplasia. Conclusions Radial scars tend to be associated with an increased breast cancer risk. Radial scars should be considered among women with proliferative disease without atypia, while atypical hyperplasia is still the primary concern among women with both radial scars and atypical hyperplasia.

Zhong, Shanliang; Chen, Weixian; Hu, Qing; Ma, Tengfei; Zhang, Jun; Zhang, Xiaohui; Tang, Jinhai; Zhao, Jianhua

2014-01-01

137

C-Reactive Protein, Interleukin 6 and Lung Cancer Risk: A Meta-Analysis  

PubMed Central

Purpose Epidemiologic findings are inconsistent concerning the associations between C-reactive protein (CRP), interleukin 6 (IL-6) and lung cancer risk. We conducted a meta-analysis of epidemiologic studies to examine these associations. Methods A systematic literature search up to October 2011 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model. Results The 10 studies on CRP involved a total of 1918 lung cancer cases. The pooled RR of lung cancer for one unit change in natural logarithm (ln) CRP was 1.28 (95% CI 1.17–1.41). There was no statistically significant heterogeneity among studies (P?=?0.116; I2?=?36.6%). We also found that CRP was significantly associated with increased risk of lung cancer among men (RR 1.18, 95% CI 1.09–1.28) but not among women. The 5 studies on IL-6 involved a total of 924 lung cancer cases. The pooled RR of lung cancer for one unit change in ln IL-6 was 1.28 (95% CI 0.92–1.79), however, statistically significant heterogeneity was found. After excluding the study contributing most to the heterogeneity, the summary estimate was essentially unchanged. Conclusion CRP was associated with increased risk of lung cancer, especially among men. There was no significant association between IL-6 and lung cancer risk.

Wang, Ze-Mu; Xi, Tao

2012-01-01

138

Methods for Cancer Epigenome Analysis  

PubMed Central

Accurate detection of epimutations in tumor cells is crucial for understanding the molecular pathogenesis of cancer. Alterations in DNA methylation in cancer are functionally important and clinically relevant, but even this well-studied area is continually re-evaluated in light of unanticipated results, including a strong connection between aberrant DNA methylation in adult tumors and polycomb group profiles in embryonic stem cells, cancer-associated genetic mutations in epigenetic regulators such as DNMT3A and TET family genes, and the discovery of abundant 5-hydroxymethylcytosine, a product of TET proteins acting on 5-methylcytosine, in human tissues. The abundance and distribution of covalent histone modifications in primary cancer tissues relative to normal cells is a largely uncharted area, although there is good evidence for a mechanistic role of cancer-specific alterations in epigenetic marks in tumor etiology, drug response and tumor progression. Meanwhile, the discovery of new epigenetic marks continues, and there are many useful methods for epigenome analysis applicable to primary tumor samples, in addition to cancer cell lines. For DNA methylation and hydroxymethylation, next-generation sequencing allows increasingly inexpensive and quantitative whole-genome profiling. Similarly, the refinement and maturation of chromatin immunoprecipitation with next-generation sequencing (ChIP-seq) has made possible genome-wide mapping of histone modifications, open chromatin and transcription factor binding sites. Computational tools have been developed apace with these epigenome methods to better enable the accuracy and interpretation of the data from the profiling methods.

Nagarajan, Raman P.; Fouse, Shaun D.; Bell, Robert J.A.; Costello, Joseph F.

2014-01-01

139

Fractionated BNCT for locally recurrent head and neck cancer: Experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.  

PubMed

To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial. PMID:24369888

Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Wang, Shyh-Jen; Chu, Pen-Yuan; Yen, Sang-Hue

2014-06-01

140

Fuel Burnup and Fuel Pool Shielding Analysis for Bushehr Nuclear Reactor VVER-1000  

NASA Astrophysics Data System (ADS)

Bushehr Nuclear power plant (BNPP) is currently under construction. The VVER-1000 reactor will be loaded with 126 tons of about 4% enriched fuel having 3-years life cycle. The spent fuel (SF) will be transferred into the spent fuel pool (SPF), where it stays for 8 years before being transferred to Russia. The SPF plays a crucial role during 8 years when the SP resides in there. This paper investigates the shielding of this structure as it is designed to shield the SF radiation. In this study, the SF isotope inventory, for different cycles and with different burnups, was calculated using WIMS/4D transport code. Using MCNP4C nuclear code, the intensity of ? rays was obtained in different layers of SFP shields. These layers include the water above fuel assemblies (FA) in pool, concrete wall of the pool and water laid above transferring fuels. Results show that ? rays leakage from the shield in the mentioned layers are in agreement with the plant's PSAR data. Finally we analyzed an accident were the water height above the FA in the pool drops to 47 cm. In this case it was observed that exposure dose above pool, 10 and 30 days from the accident, are still high and in the levels of 1000 and 758 R/hr.

Hadad, Kamal; Ayobian, Navid

141

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts  

PubMed Central

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (?50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

2012-01-01

142

Examining the Efficacy of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Analysis of 2 Studies  

PubMed Central

Background: Patients with major depressive disorder (MDD) who fail to achieve complete remission with antidepressant therapy may benefit from augmentation therapy with an atypical antipsychotic. Method: A pooled analysis was performed on 2 identical 14-week studies (8-week prospective antidepressant therapy treatment phase followed by 6-week randomized double-blind phase) evaluating the efficacy of adjunctive aripiprazole (2–20 mg/day) in DSM-IV-TR–defined MDD patients with an inadequate response to antidepressant therapy. Primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of the prospective phase (week 8) to end of randomized phase (week 14, last observation carried forward). Subgroup analyses were performed. The key secondary endpoint was mean change in Sheehan Disability Scale (SDS) mean score. Results: At endpoint, mean change in MADRS total score was significantly greater with adjunctive aripiprazole (–8.7) than with adjunctive placebo (–5.7; p < .001). Except for a differential treatment-by-sex interaction, change in MADRS total scores were consistently greater with adjunctive aripiprazole than with adjunctive placebo, regardless of race, age, episode duration, prior antidepressant therapy response, number of historical treatment failures, severity of depressive symptoms, and antidepressant. At endpoint, MADRS remission rates were significantly greater with adjunctive aripiprazole than with placebo (25.7% vs. 15.4%; p < .001). Adjunctive aripiprazole also demonstrated significantly greater improvements in mean change from baseline in SDS total score than adjunctive placebo (–1.2 vs. –0.6; p = .001). Conclusion: Augmentation of antidepressant therapy with the atypical antipsychotic aripiprazole resulted in significant efficacy benefits across a range of subgroups of patients with MDD. Further study of a treatment-by-sex interaction is needed. Trial Registration: www.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758

Thase, Michael E.; Trivedi, Madhukar H.; Nelson, J. Craig; Fava, Maurizio; Swanink, Rene; Tran, Quynh-Van; Pikalov, Andrei; Yang, Huyuan; Carlson, Berit X.; Marcus, Ronald N.; Berman, Robert M.

2008-01-01

143

Prognostic Value of miR-21 in Various Cancers: An Updating Meta-Analysis  

PubMed Central

Background Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. Methods We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Results The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66–2.19) for OS, 1.42 (95% CI: 1.16–1.74) for DFS and 2.2 (95% CI: 1.64–2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18–4.9) for OS. Conclusions Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical.

Huang, Zebo; Wang, Jian; Zhu, Wei; Shu, Yongqian; Liu, Ping

2014-01-01

144

Immediate placement of dental implants in the esthetic zone: a systematic review and pooled analysis.  

PubMed

Background: Research interest on immediate placement of dental implants has shifted from implant survival toward optimal preservation of soft and hard tissues. The aim of this study is to systematically assess the condition of implant survival, peri-implant hard and soft tissue changes, esthetic outcome, and patient satisfaction of immediately placed single-tooth implants in the esthetic zone. Methods: MEDLINE, EMBASE, and CENTRAL databases were searched for publications up to June 2013. Studies reporting on implant survival, changes in hard and soft peri-implant tissues, esthetic outcome, and patient satisfaction were considered. A pooled analysis was performed to identify factors associated with survival and peri-implant tissue changes after immediate implant placement. Results: Thirty-four studies were considered eligible. Immediate placement of single-tooth implants in the esthetic zone was accompanied by excellent 1-year implant survival (97.1%, 95% confidence interval [CI]: 0.958 to 0.980). Mean marginal peri-implant bone loss was 0.81 ± 0.48 mm, mean loss of interproximal peri-implant mucosa level was 0.38 ± 0.23 mm, and mean loss of peri-implant midfacial mucosa level was 0.54 ± 0.39 mm. Regression analysis revealed that delayed provisionalization (odds ratio [OR] 58.03, 95% CI: 8.05 to 418.41, P <0.000), use of a flap (OR 19.87, 95% CI: 10.21 to 38.66, P <0.000), and use of a connective tissue graft (OR 4.56, 95% CI: 1.72 to 12.08, P <0.002) were associated with marginal peri-implant bone-level change >0.50 mm. Because of underreporting, esthetic results and patient outcome did not allow for reliable analysis. Conclusion: Immediate placement with immediate provisionalization of dental implants in the esthetic zone results in excellent short-term treatment outcome in terms of implant survival and minimal change of peri-implant soft and hard tissue dimensions. PMID:24502614

Slagter, Kirsten W; den Hartog, Laurens; Bakker, Nicolaas A; Vissink, Arjan; Meijer, Henny J A; Raghoebar, Gerry M

2014-07-01

145

Diagnostic performance of serum macrophage inhibitory cytokine-1 in pancreatic cancer: a meta-analysis and meta-regression analysis.  

PubMed

Many existing studies have demonstrated that the macrophage inhibitory cytokine-1 (MIC-1) might be a powerful diagnostic biomarker in patients with pancreatic cancer; but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the diagnostic performance of serum MIC-1 in pancreatic cancer. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. Meta-analysis was performed using Meta-Disc version 1.4 and STATA version 12.0 software. Crude standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Ten case-control studies were included in this meta-analysis with a total of 1235 pancreatic cancer patients and 730 healthy subjects. Our meta-analysis results revealed that serum MIC-1 levels in pancreatic patients were higher than those of healthy subjects (SMD=1.38, 95% CI=1.15-1.62, p<0.001). The area under the SROC curve was 0.92 (SE=0.020); the pooled sensitivity was 0.79 (95% CI=0.77-0.82); and the pooled specificity was 0.86 (95% CI=0.84-0.88). The pooled positive LR was 6.20 (95% CI=1.24-30.91); the pooled DOR was 35.73 (95% CI=18.52-68.93). In conclusion, the present meta-analysis suggests that serum MIC-1 may be a useful diagnostic biomarker with high sensitivity and specificity for identifying pancreatic cancer. PMID:24592997

Chen, Yan-Zhi; Liu, Dan; Zhao, Yu-Xia; Wang, He-Tong; Gao, Ya; Chen, Ying

2014-06-01

146

Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies  

PubMed Central

Epidemiologic studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE, and Web of Science through the end of April, 2012. Two authors (T-TG and Q-JW) independently assessed eligibility and extracted data. We pooled the relative risks (RR) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case-control and 5 cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared with the youngest category) and ovarian cancer risk (RR=0.85; 95% confidence interval (95% CI) 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case-control studies were 0.89 (95% CI 0.76–1.03) and 0.84 (95% CI 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most sub-groups, but the association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify results by different cancer grading and histotype of ovarian cancer.

Gong, Ting-Ting; Wu, Qi-Jun; Vogtmann, Emily; Lin, Bei; Wang, Yong-Lai

2013-01-01

147

Personal hair dye use and bladder cancer: a meta-analysis.  

PubMed

Despite considerable research, the issue of hair dyes and bladder cancer is still open to discussion. In January 2013, we searched in PubMed/EMBASE to identify observational studies investigating the association between personal use of hair dyes and bladder cancer incidence/mortality. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Fifteen case-control and two cohort studies were available for meta-analysis (8504 cases/deaths, 14,102 controls, and 617,937 persons at risk). Compared with no use, the pooled RR of bladder cancer for personal use of any type of hair dyes was 0.93 (95% CI, 0.82-1.05), with moderate heterogeneity among studies (I(2) = 34.1%, P = .07). Similar RRs were found for females (RR = 0.95) and males (RR = 0.81). Based on seven studies, the pooled RR for personal use of permanent hair dyes was 0.92 (95% CI, 0.77-1.09). Compared with no use, no association was observed for the highest categories of duration of use and lifetime frequency of use of both any type of dyes and permanent dyes. The pooled RR from four studies reporting results for use of dark-colored dyes was 1.29 (95% CI, 0.98-1.71). This meta-analysis allows to definitively exclude any appreciable excess risk of bladder cancer among personal hair dye users. PMID:24342029

Turati, Federica; Pelucchi, Claudio; Galeone, Carlotta; Decarli, Adriano; La Vecchia, Carlo

2014-02-01

148

Stable isotope analysis reveals lower-order river dissolved inorganic carbon pools are highly dynamic.  

PubMed

River systems draining peaty catchments are considered a source of atmospheric CO2,thus understanding the behavior of the dissolved inorganic carbon pool (DIC) is valuable. The carbon isotopic composition, delta13C(DIC), and concentration, [DIC], of fluvial samples collected diurnally, over 14 months, reveal the DIC pools to be dynamic in range (-22 to -4.9% per hundred, 0.012 to 0.468 mmol L(-1) C), responding predictably to environmental influences such as changing hydrologic conditions or increased levels of primary production. delta(18)O of dissolved oxygen (DO) corroborates the delta(13)C(DIC) interpretation. A nested catchment sampling matrix reveals that similar processes affect the DIC pool and thus delta(13)C(DIC) across catchment sizes. Not so with [DIC]: at high flow, the DIC export converges across catchment size, but at low flow catchments diverge in their DIC load. Contextualizing delta(13)C with discharge reveals that organic soil-waters and groundwaters comprise end-member sources, which in varying proportions constitute the fluvial DIC pool. Discharge and pH describe well [DIC] and delta(13)C(DIC), allowing carbon to be apportioned to each end-member from continuous profiles, demonstrated here for the hydrological year 2003-2004. This approach is powerful for assessing whether the dynamic response exhibited here is ubiquitous in other fluvial systems at the terrestrial-aquatic interface or in larger catchments. PMID:17937296

Waldron, Susan; Scott, E Marian; Soulsby, Chris

2007-09-01

149

Association Between the NFKB1-94ins/del ATTG Polymorphism and Cancer Risk: An Updated Meta-Analysis.  

PubMed

To assess the effect of the NFKB1 -94ins/del polymorphism on cancer, we conducted a meta-analysis based on 25 studies including 8,750 cases and 9,170 controls. Overall, the -94ins/del polymorphism was associated with cancer risk in the pooled analysis and in Asian population, whereas no association was observed in Caucasian population. Stratified analysis by subtypes of cancer showed that the -94ins/del polymorphism was associated with oral squamous cell carcinoma and ovarian cancer risk, but had no association with colorectal cancer, bladder cancer, and renal cell cancer. Our meta-analysis suggests the NFKB1 -94ins/del polymorphism affects cancer susceptibility, and the association is ethnic-specific. PMID:24827594

Duan, Wenyuan; Wang, Erli; Zhang, Fengquan; Wang, Tongjian; You, Xiangdong; Qiao, Bin

2014-08-01

150

Prognostic value of circulating microRNA-21 in digestive system cancers: a meta-analysis  

PubMed Central

Circulating microRNAs show aberrant expression in patients with cancer. The aim of this study was to investigate the prognostic value of circulating microRNA-21 (miR-21) in digestive system cancers. Methods: All the eligible studies were searched by Medline and EMBASE. The hazard ratios (HRs) for overall survival (OS), which compared the expression levels of circulating miR-21 in patients with digestive cancer was extracted and estimated. Pooled HRs and 95% confidence intervals (CI) were calculated. Then a meta-analysis was performed to clarify the prognostic value of the miR-21. Results: A total of seven studies involving 907 subjects were included. The results suggested that higher circulating miR-21 could predict worse OS outcome with the pooled HR of 2.19 (95% CI 1.01-4.75, P = 0.05) in digestive system cancers. Subgroup analysis by ethnicity indicated circulating miR-21 was associated with OS in patients with digestive cancer among Asians with the pooled HR of 2.90 (95% CI 1.30-6.45, P = 0.009). However, subgroup analysis by digestive system site revealed that there is no associated with OS in patients with colorectal cancer with the pooled HR of 1.34 (95% CI 0.45-4.00, P = 0.60). Conclusion: The present findings suggest that circulating miR-21 is associated with poor survival in patients with digestive cancer and could be a prognostic biomarker for those patients.

Ye, Ting-Ting; Yang, Yin-Long; Liu, Xin-Ying; Ji, Qian-Qing; Pan, Yi-Fei; Xiang, You-Qun

2014-01-01

151

The Association of Telomere Length and Cancer: A Meta-Analysis  

PubMed Central

Background Telomeres shorten with each cell division and are essential for chromosomal stability. Short telomeres in surrogate tissues (e.g., blood cells) are associated with increased cancer risk in several case-control studies, but findings are inconsistent in prospective studies. Methods We systematically reviewed studies published prior to August 30, 2010 on the association between telomere length (TL) in surrogate tissues and cancer. There were 27 reports on 13 cancers and/or incident cancer investigating this association. The majority, 16, were retrospective case-control studies, 11 were prospective studies. Meta-analyses were conducted to determine odds ratios (ORs) and 95% confidence intervals (CIs) for these studies. Results Studies on bladder, esophageal, gastric, head and neck, ovarian, renal, and overall incident cancer found associations between short telomeres and these cancers. Non-Hodgkin lymphoma, breast, lung and colorectal cancer reports were inconsistent. Single studies on endometrial, prostate, and skin cancers were null. In a random effects meta-analysis, short TL was significantly associated with cancer in retrospective studies (pooled OR for the shortest TL quartile compared with the longest: 2.9, 95%CI 1.73 – 4.8, P<0.0001). The pooled OR for prospective studies was 1.16 (95%CI 0.87 – 1.54, P=0.32). All studies combined yielded a pooled OR of 1.96 (95%CI 1.37 – 2.81, P=0.0001) for the association of short TL and cancer. Conclusion and Impact There is suggestive evidence that short surrogate tissue TL is associated with cancer; the strongest evidence exists for bladder, esophageal, gastric, and renal cancers. Additional prospective studies with consistent methodology are needed to confirm this hypothesis.

Wentzensen, Ingrid M.; Mirabello, Lisa; Pfeiffer, Ruth M.; Savage, Sharon A.

2011-01-01

152

Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials  

PubMed Central

Objectives To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane (123I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies. Design Pooled analysis of three phase 3 and one phase 4 clinical trials. These four trials were selected because they were the four studies used for the US new drug application to the Food and Drug Administration (FDA). Setting Multicentre, open-label, non-randomised. Participants Patients with either a movement disorder or dementia, and healthy volunteers. Interventions Ioflupane (123I) was administered. Outcome measures Images were assessed by panels of 3–5 blinded experts and/or on-site nuclear medicine physicians, classified as normal or abnormal and compared with clinical diagnosis (reference standard) to determine sensitivity and specificity. Results Pooling the four studies, 928 participants were enrolled, 849 were dosed and 764 completed their study. Across all studies, when images were assessed by on-site readers, ioflupane (123I) diagnostic effectiveness had an overall (95% CI) sensitivity of 91.9% (88.7% to 94.5%) and specificity of 83.6% (78.7% to 87.9%). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8% to 90.4%) and specificity was 91.2% (89.0% to 93.0%). Conclusions In this pooled analysis, the visual assessment of ioflupane (123I) images provided high levels of sensitivity and specificity in detecting the presence/absence of an SDDD. Ioflupane (123I) imaging has the potential to improve diagnostic accuracy in patients with signs and symptoms of a movement disorder and/or dementia. Trial registration number NCT00209456.

O'Brien, John T; Oertel, Wolfgang H; McKeith, Ian G; Grosset, Donald G; Walker, Zuzana; Tatsch, Klaus; Tolosa, Eduardo; Sherwin, Paul F; Grachev, Igor D

2014-01-01

153

An Innovative Hybrid Loop-Pool SFR Design and Safety Analysis Methods: Today and Tomorrow  

SciTech Connect

Investment in commercial sodium cooled fast reactor (SFR) power plants will become possible only if SFRs achieve economic competitiveness as compared to light water reactors and other Generation IV reactors. Toward that end, we have launched efforts to improve the economics and safety of SFRs from the thermal design and safety analyses perspectives at Idaho National Laboratory. From the thermal design perspective, an innovative hybrid loop-pool SFR design has been proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to further improve economics and safety. From the safety analyses perspective, we have initiated an effort to develop a high fidelity reactor system safety code.

Hongbin Zhang; Haihua Zhao; Vincent Mousseau

2008-04-01

154

A keyhole volumetric model for weld pool analysis in Nd:YAG pulsed laser welding  

NASA Astrophysics Data System (ADS)

This study presents a new model for analyzing the temperature distribution and weld pool shape in Nd:YAG pulsed laser welding. In the proposed approach, a surface flux heat transfer model is applied in the low laser energy intensity region of the weld, while a keyhole heat transfer model based on a volumetric heat source is applied in the high laser energy intensity region of the weld. The correlation between the intensity of the laser input energy and the geometric parameters of the volumetric heat source is derived experimentally. A series of MARC finite element simulations based on the proposed single pulse model are performed to investigate the shape and size of the weld pool given different laser energy intensities. A good agreement is observed between the simulation results and the experimental results obtained under equivalent single pulse welding conditions. Thus, the basic validity of the proposed model is confirmed.

Kuang, Jao-Hwa; Hung, Tsung-Pin; Chen, Chih-Kuan

2012-07-01

155

Impact of community based, specialist palliative care teams on hospitalisations and emergency department visits late in life and hospital deaths: a pooled analysis  

PubMed Central

Objective To determine the pooled effect of exposure to one of 11 specialist palliative care teams providing services in patients’ homes. Design Pooled analysis of a retrospective cohort study. Setting Ontario, Canada. Participants 3109 patients who received care from specialist palliative care teams in 2009-11 (exposed) matched by propensity score to 3109 patients who received usual care (unexposed). Intervention The palliative care teams studied served different geographies and varied in team composition and size but had the same core team members and role: a core group of palliative care physicians, nurses, and family physicians who provide integrated palliative care to patients in their homes. The teams’ role was to manage symptoms, provide education and care, coordinate services, and be available without interruption regardless of time or day. Main outcome measures Patients (a) being in hospital in the last two weeks of life; (b) having an emergency department visit in the last two weeks of life; or (c) dying in hospital. Results In both exposed and unexposed groups, about 80% had cancer and 78% received end of life homecare services for the same average duration. Across all palliative care teams, 970 (31.2%) of the exposed group were in hospital and 896 (28.9%) had an emergency department visit in the last two weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the unexposed group (P<0.001). The pooled relative risks of being in hospital and having an emergency department visit in late life comparing exposed versus unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to 0.86) respectively. Fewer exposed than unexposed patients died in hospital (503 (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in hospital was 0.46 (0.40 to 0.52). Conclusions Community based specialist palliative care teams, despite variation in team composition and geographies, were effective at reducing acute care use and hospital deaths at the end of life.

Brazil, Kevin; Sussman, Jonathan; Pereira, Jose; Marshall, Denise; Austin, Peter C; Husain, Amna; Rangrej, Jagadish; Barbera, Lisa

2014-01-01

156

Thermal analysis of five unglazed solar collector systems for the heating of outdoor swimming pools  

SciTech Connect

The performance and behavior of five unglazed solar collector installations, devoted to the heating of five outdoor swimming pools located in Switzerland, is studied on the basis of experimental data collected in 1988. Due to the low temperatures involved, hourly efficiencies often exceed 80%. The mean daily collector efficiency is of the order of 60% in optimal conditions and is in good agreement with the G3 simulation program.

Molineaux, B.; Lachal, B.; Guisan, O. (Univ. of Genva (Switzerland))

1994-07-01

157

NaK pool-boiler solar receiver durability bench test. Volume 2: Metallurgical analysis  

NASA Astrophysics Data System (ADS)

The principal materials used in the construction of a NaK based pool-boiler were analyzed. The device, operated for 7500 hours, accumulated 1000 thermal cycles to a peak temperature of 750 C. Haynes 230, used to fabricate the pool-boiler vessel, was found to perform satisfactorily. Air-side corrosion of the pool-boiler vessel was insignificant. Internal surface of the alloy exhibited some NaK-induced elemental dissolution; this dissolution was somewhat more extensive where the alloy was exposed to the liquid metal compared to regions exposed only to NaK vapor; however, the corresponding metal loss in all regions was inconsequential, never exceeding more than a few microns. Autogenous seam welds of the alloy responded in a similar fashion, exhibiting only minimal metal loss over the course of the experiment. While there was 50% loss in ductility of the alloy there remained adequate ductility for the anticipated operating environment. An enhanced boiling nucleation surface comprised of stainless steel powder brazed to the vessel ID showed no change in its structure. It remained intact, showing no cracking after repeated thermal cycling. Other materials used in the experiment showed more extensive degradation after exposure to the NaK. IN 600, used to fabricate thermowells, exhibited extensive surface and intergranular dissolution. Grain boundary dissolution was sufficiently severe in one of the thermowells to cause an air leak, resulting in experiment termination. BNi-3, a brazing alloy used to join the pool-boiler vessel, endcaps and thermowells, showed some dissolution where it was exposed to the NaK as well as thermal aging effects. However, all brazes remained structurally sound. A nickel metal ribbon showed catastrophic dissolution, resulting in the formation of deep (greater than 30 (mu)m) pits and cavities. A zirconium metal foil used to getter oxygen from the NaK became extremely brittle.

Goods, S. H.; Bradshaw, R. W.

1995-01-01

158

Phylogenetic analysis of Archaea in the deep-sea sediments of west Pacific Warm Pool  

Microsoft Academic Search

Archaea are known to play important roles in carbon cycling in marine sediments. The main compositions of archaeal community in five deep-sea sediment samples collected from west Pacific Warm Pool area (WP-0, WP-1, WP-2, WP-3, WP-4), and in five sediment layers (1 cm-, 3 cm-, 6 cm-, 10 cm-, 12 cm- layer) of the 12 cm sediment core of WP-0 were checked and compared by denaturing

Peng Wang; Xiang Xiao; Fengping Wang

2005-01-01

159

Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene.  

PubMed

A genome-wide association analysis using the Affymetrix 100K SNP array was carried out in a case-control study of lung cancer. Allele frequencies were estimated initially in DNA pools. Significant differences in allele frequency detected in the SNP array analysis were first tested in the same DNA pools by pyrosequencing and then by individual genotyping. DNA pooling analysis identified rs10508266 SNP, located approximately 12.5kb from the 5'-end of the KLF6 gene, as a marker showing significant association with lung cancer risk. Since the SNP was in significant linkage disequilibrium with the KLF6 gene region, we analyzed an Italian population of 338 lung adenocarcinoma cases and 335 controls for the possible role of the reported functional rs3750861 SNP, located 15.6kb from the rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of 265 non small cell lung cancer cases, and 356 controls, however, did not confirm the association. In light of the reported functional involvement of the KLF6 gene in lung cancer and in other cancer types and to the functional nature of the rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk, although additional studies in large series are needed to confirm our findings and to elucidate the mechanism by which the KLF6 SNPs influence lung cancer risk. PMID:17223258

Spinola, Monica; Leoni, Vera P; Galvan, Antonella; Korsching, Eberhard; Conti, Barbara; Pastorino, Ugo; Ravagnani, Fernando; Columbano, Amedeo; Skaug, Vidar; Haugen, Aage; Dragani, Tommaso A

2007-06-28

160

Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice  

PubMed Central

Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS).

Porwollik, Steffen; Choi, Sang-Ho; Long, Fred; Andrews-Polymenis, Helene L.; McClelland, Michael

2009-01-01

161

A comparative analysis of dietary intakes during pregnancy in Europe: a planned pooled analysis of birth cohort studies1234  

PubMed Central

Background: There is growing evidence that despite the absence of marked deficiencies, diet during pregnancy has important implications for maternal and child health in industrialized countries. At present, relatively little is known about prevailing patterns of intake across groups with diverse sociodemographic and lifestyle patterns in these settings. Objectives: The aims of this study were to develop methods for the standardization of food group intake data and to describe the process of applying these methods to existing pregnancy cohort studies, which included >200,000 women across Europe. Design: The study developed a detailed standardization protocol to harmonize intakes of selected food groups, which included fruit, vegetables, meats, seafood, and dairy products. Standardization is necessary to facilitate valid comparisons of intake patterns and disparities across countries and will lead to the development of harmonized databases for possible future pooled analyses. Results: On the basis of comparisons with previously coordinated multicountry studies, preliminary data suggest that the standardization process yielded sufficiently comparable intake data, which indicate differences in food cultures across the countries that participated. Conclusions: This project provides lessons on the feasibility of harmonizing dietary intake data from existing studies, which can be applied in future post hoc standardization efforts. The data yielded in this analysis will also provide useful information for the development of food and nutrition policies for pregnant women in Europe, including the identification of population subgroups in which dietary inadequacies during pregnancy may be widespread.

Kogevinas, Manolis

2011-01-01

162

Grant pool  

Microsoft Academic Search

The Grant Pool, Harper County, Kans., is a structural trap in both the Mississippian and Simpson reservoirs. It has stong closure in all directions and is located on a weak, NE. trending regional Ordovician ridge. The Mississippian reservoir has very shallow weathering with chat grading to fresh chert in the top 15 ft. The Simpson reservoir consists of approximately 30

Devlin

1965-01-01

163

Pooled Analysis of Non-Union, Re-Operation, Infection, and Approach Related Complications after Anterior Odontoid Screw Fixation  

PubMed Central

Background Anterior odontoid screw fixation (AOSF) has been one of the most popular treatments for odontoid fractures. However, the true efficacy of AOSF remains unclear. In this study, we aimed to provide the pooled rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid fractures. Methods We searched studies that discussed complications after AOSF for type II or type III odontoid fractures. A proportion meta-analysis was done and potential sources of heterogeneity were explored by meta-regression analysis. Results Of 972 references initially identified, 63 were eligible for inclusion. 54 studies provided data regarding non-union. The pooled non-union rate was 10% (95% CI: 7%–3%). 48 citations provided re-operation information with a pooled proportion of 5% (95% CI: 3%–7%). Infection was described in 20 studies with an overall rate of 0.2% (95% CI: 0%–1.2%). The main approach related complication is postoperative dysphagia with a pooled rate of 10% (95% CI: 4%–17%). Proportions for the other approach related complications such as postoperative hoarseness (1.2%, 95% CI: 0%–3.7%), esophageal/retropharyngeal injury (0%, 95% CI: 0%–1.1%), wound hematomas (0.2%, 95% CI: 0%–1.8%), and spinal cord injury (0%, 95% CI: 0%–0.2%) were very low. Significant heterogeneities were detected when we combined the rates of non-union, re-operation, and dysphagia. Multivariate meta-regression analysis showed that old age was significantly predictive of non-union. Subgroup comparisons showed significant higher non-union rates in age ?70 than that in age ?40 and in age 40 to <50. Meta-regression analysis did not reveal any examined variables influencing the re-operation rate. Meta-regression analysis showed age had a significant effect on the dysphagia rate. Conclusions/Significances This study summarized the rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid factures. Elderly patients were more likely to experience non-union and dysphagia.

Tian, Nai-Feng; Hu, Xu-Qi; Wu, Li-Jun; Wu, Xin-Lei; Wu, Yao-Sen; Zhang, Xiao-Lei; Wang, Xiang-Yang; Chi, Yong-Long; Mao, Fang-Min

2014-01-01

164

Kinesiologic taping reduces morbidity after oral and maxillofacial surgery: a pooled analysis.  

PubMed

Abstract Background: Postoperative morbidity is a major disadvantage after oral and maxillofacial (OMF) surgery, often caused by pain, trismus and swelling affecting patients' quality of life. The goal of this study was to examine the effect of kinesiologic taping (KT) on swelling, pain, trismus and patients' satisfaction after OMF surgery. Materials and methods: Performing a pooled analysis of 96 patients that were assigned for maxillofacial treatment (midface fractures n?=?30, mandibular fractures n?=?26, wisdom tooth removal n?=?40) divided into treatment either with or without kinesiologic tape application. Tape was applied directly after surgery and maintained for at least 5?d postoperatively. Facial swelling was quantified at six specific points in time using a five-line measurement. Pain and degree of mouth opening was measured. Patients' objective feeling and satisfaction was queried. Results: Application of KT after OMF surgery has a significant influence on the reduction of swelling decreasing the turgidity for 60% during the first 2?d after surgery. Evaluating all patients swelling was significantly lower in the KT treatment group (T2: 63.5?cm?±?4.3; T3: 62.5?cm?±?4.2; T4: 61.6?cm?±?4.2) than in the no-KT group (T2: 67.6?cm?±?5.0; T3: 67.0?cm?±?5.0; T4: 64.8?cm?±?4.8) at T2 (p?

Ristow, Oliver; Pautke, Christoph; Kehl, Victoria; Koerdt, Steffen; Hahnefeld, Lilian; Hohlweg-Majert, Bettina

2014-08-01

165

Probabilistic risk analysis for Test Area North Hot Shop Storage Pool Facility  

SciTech Connect

A storage pool facility used for storing spent fuel and radioactive debris from the Three Mile Island (TMI) accident was evaluated to determine the risk associated with its normal operations. Several hazards were identified and examined to determine if any any credible accident scenarios existed. Expected annual occurrence frequencies were calculated for hazards for which accident scenarios were identified through use of fault trees modeling techniques. Fault tree models were developed for two hazards: (1) increased radiation field and (2) spread of contamination. The models incorporated facets of the operations within the facility as well as the facility itself. 6 refs.

Meale, B.M.; Satterwhite, D.G.

1990-01-01

166

Analgesic use and the risk of kidney cancer: a meta-analysis of epidemiologic studies  

PubMed Central

Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for 3 categories of analgesics: acetaminophen, aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin, and 5 with other NSAIDs) that were performed in 6 countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR, 1.28; 95% CI, 1.15 to 1.44 and 1.25; 95% CI, 1.06 to 1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR, 1.10; 95% CI, 0.95 to 1.28), except for non-US studies (5 studies, pooled RR=1.17, 95% CI, 1.04 to 1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings.

Choueiri, Toni K.; Je, Youjin; Cho, Eunyoung

2013-01-01

167

Variation in cancer risk estimates for exposure to powerline frequency electromagnetic fields: A meta-analysis comparing EMF measurement methods  

SciTech Connect

We used meta-analysis to synthesize the findings from eleven case-control studies on cancer risks in humans exposed to 50-60 Hertz powerline electromagnetic fields (EMFs). Pooled estimates of risk are derived for different EMF measurement methods and types of cancer. EMF measurement methods are classified as: wiring configuration codes, distance to power distribution equipment, spot measurements of magnetic fields, and calculated indices based on distance to power distribution equipment and historic load data. Pooled odds ratios depicting the risk of cancer by each measurement type are presented for all cancers combined, leukemia for all age groups and childhood leukemia. The wire code measurement technique was associated with a significantly increased risk for all three cancer types, while spot measures consistently showed non-significant odds ratios. Distance measures and the calculated indices produced risk estimates which were significant only for leukemia. 24 refs., 6 tabs.

Miller, M.A.; Murphy, J.R.; MIller, T. I; Ruttenber, A.J. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)

1995-04-01

168

An HLA-DR-Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2-Specific Immunity in Patients with Cancer  

PubMed Central

Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I–based vaccines. In this study, the goal was to identify an HLA-DR–degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1–binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-? enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization.

Kalli, Kimberly R.; Krco, Christopher J.; Hartmann, Lynn C.; Goodman, Karin; Maurer, Matthew J.; Yu, Chao; Johnson, Elliot M.; Erskine, Courtney L.; Disis, Mary L.; Wettstein, Peter J.; Fikes, John D.; Beebe, Melanie; Ishioka, Glenn; Knutson, Keith L.

2009-01-01

169

Cellular Levels of 8-Oxoguanine in either DNA or the Nucleotide Pool Play Pivotal Roles in Carcinogenesis and Survival of Cancer Cells.  

PubMed

8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation of the DNA guanine base. MTH1, also known as NUDT1, with 8-oxo-dGTP hydrolyzing activity, 8-oxoguanine DNA glycosylase (OGG1) an 8-oxoG DNA glycosylase, and MutY homolog (MUTYH) with adenine DNA glycosylase activity, minimize the accumulation of 8-oxoG in DNA; deficiencies in these enzymes increase spontaneous and induced tumorigenesis susceptibility. However, different tissue types have different tumorigenesis susceptibilities. These can be reversed by combined deficiencies in the defense systems, because cell death induced by accumulation of 8-oxoG in DNA is dependent on MUTYH, which can be suppressed by MTH1 and OGG1. In cancer cells encountering high oxidative stress levels, a high level of 8-oxo-dGTP accumulates in the nucleotide pool, and cells therefore express increased levels of MTH1 in order to eliminate 8-oxo-dGTP. Suppression of MTH1 may be an efficient strategy for killing cancer cells; however, because MTH1 and OGG1 protect normal tissues from oxidative-stress-induced cell death, it is important that MTH1 inhibition does not increase the risk of healthy tissue degeneration. PMID:25029543

Nakabeppu, Yusaku

2014-01-01

170

Heat transfer from horizontal tubes in pool boiling: influence of three-dimensional heat conduction in the wall of the evaporator tube—a finite element analysis  

Microsoft Academic Search

In pool boiling, the electrically heated tube releases the energy non-uniformly to the liquid, due to different surface roughness\\u000a and flowing liquid. The heat transfer coefficient therefore varies with axial and azimuthal position on the tube. Hence a\\u000a finite element analysis has been carried out on a horizontal 1in. copper tube for evaporation in pool boiling for three-dimensional\\u000a conduction heat

C. Ranganayakulu; Gerhard Herres

2006-01-01

171

Individual and setting level predictors of the implementation of a skin cancer prevention program: a multilevel analysis  

PubMed Central

Background To achieve widespread cancer control, a better understanding is needed of the factors that contribute to successful implementation of effective skin cancer prevention interventions. This study assessed the relative contributions of individual- and setting-level characteristics to implementation of a widely disseminated skin cancer prevention program. Methods A multilevel analysis was conducted using data from the Pool Cool Diffusion Trial from 2004 and replicated with data from 2005. Implementation of Pool Cool by lifeguards was measured using a composite score (implementation variable, range 0 to 10) that assessed whether the lifeguard performed different components of the intervention. Predictors included lifeguard background characteristics, lifeguard sun protection-related attitudes and behaviors, pool characteristics, and enhanced (i.e., more technical assistance, tailored materials, and incentives are provided) versus basic treatment group. Results The mean value of the implementation variable was 4 in both years (2004 and 2005; SD = 2 in 2004 and SD = 3 in 2005) indicating a moderate implementation for most lifeguards. Several individual-level (lifeguard characteristics) and setting-level (pool characteristics and treatment group) factors were found to be significantly associated with implementation of Pool Cool by lifeguards. All three lifeguard-level domains (lifeguard background characteristics, lifeguard sun protection-related attitudes and behaviors) and six pool-level predictors (number of weekly pool visitors, intervention intensity, geographic latitude, pool location, sun safety and/or skin cancer prevention programs, and sun safety programs and policies) were included in the final model. The most important predictors of implementation were the number of weekly pool visitors (inverse association) and enhanced treatment group (positive association). That is, pools with fewer weekly visitors and pools in the enhanced treatment group had significantly higher program implementation in both 2004 and 2005. Conclusions More intense, theory-driven dissemination strategies led to higher levels of implementation of this effective skin cancer prevention program. Issues to be considered by practitioners seeking to implement evidence-based programs in community settings, include taking into account both individual-level and setting-level factors, using active implementation approaches, and assessing local needs to adapt intervention materials.

2010-01-01

172

COX-2-765G>C Polymorphism Increases the Risk of Cancer: A Meta-Analysis  

PubMed Central

Background Chronic inflammation has been regarded as an important mechanism in carcinogenesis. Inflammation-associated genetic variants have been highly associated with cancer risk. Polymorphisms in the gene cyclooxygenase-2 (COX-2), a pro-inflammation factor, have been suggested to alter the risk of multiple tumors, but the findings of various studies are not consistent. Methods A literature search through February 2013 was performed using PubMed, EMBASE, and CNKI databases. We used odds ratios (ORs) with confidence intervals (CIs) of 95% to assess the strength of the association between the COX-2-765G>C polymorphism and cancer risk in a random-effect model. We also assessed heterogeneity and publication bias. Results In total, 65 articles with 29,487 cancer cases and 39,212 non-cancer controls were included in this meta-analysis. The pooled OR (95% CIs) in the co-dominant model (GC vs. GG) was 1.11 (1.02–1.22), and in the dominant model ((CC+GC) vs. GG), the pooled OR was 1.12 (1.02–1.23). In the subgroup analysis, stratified by cancer type and race, significant associations were found between the-765 C allele and higher risk for gastric cancer, leukemia, pancreatic cancer, and cancer in the Asian population. Conclusion In summary, the COX-2-765 C allele was related to increased cancer susceptibility, especially gastric cancer and cancer in the Asian population.

Zhang, Xiao-wei; Hua, Rui-xi; Guo, Wei-jian

2013-01-01

173

Plasma effect on weld pool surface reconstruction by shape-from-polarization analysis  

NASA Astrophysics Data System (ADS)

The polarimetric state of the thermal radiations emitted by the weld metal contains geometric information about the emitting surface. Even though the analysed thermal radiation has a wavelength corresponding to a blind spectral window of the arc plasma, the physical presence of the arc plasma itself interferes with the rays radiated by the weld pool surface before attaining the polarimeter, thus modifying the geometric information transported by the ray. In the present work, the effect of the arc plasma-surrounding zone on the polarimetric state and propagation direction of the radiated ray is analyzed. The interaction with the arc plasma zone induces a drop in ray intensity and a refraction of ray optical path.

Coniglio, N.; Mathieu, A.; Aubreton, O.; Stolz, C.

2014-03-01

174

Analysis of the pool critical assembly pressure vessel benchmark using pentran  

SciTech Connect

The internationally circulated Pool Critical Assembly (PCA) Pressure Vessel Benchmark was analyzed using the PENTRAN Parallel Sn code system for the geometry, material, and source specifications as described in the PCA Benchmark documentation. This research focused on utilizing the BUGLE-96 cross section library and accompanying reaction rates, while examining both adaptive differencing on a coarse mesh basis as well as Directional Theta Weighted Sn differencing in order to compare the calculated PENTRAN results to measured data. The results show good comparison with the measured data as well as to the calculated results provided from TORT for the BUGLE-96 cross sections and reaction rates, which suggests PENTRAN is a viable and reliable code system for calculation of light water reactor neutron shielding and dosimetry calculations. (authors)

Edgar, C. A.; Sjoden, G. E. [Nuclear and Radiological Engineering Program, George W. Woodruff School of Mechanical Engineering, Georgia Inst. of Technology, 770 State St, Atlanta, GA 30332-0745 (United States)

2012-07-01

175

Analysis of gravity anomaly over coral-reef oil field: Wilfred Pool, Sullivan County, Indiana  

SciTech Connect

To compare the measured and theoretical gravity anomaly of a typical coral-reef oil field, data were collected from the wilfred Pool, Sullivan County, Indiana. Densities of available core samples from the field were determined and the anomaly was calculated, taking into account the lateral and vertical variation of density and the geologic structure known from core studies and drilling-log records of lithologic types penetrated by the wells. Comparison of the theoretical and actual anomalies indicated a rough correspondence except for several sharp negative anomalies on the flanks of the measured gravity anomaly. Further studies indicated that the negative anomalies are possibly due to fluvial erosion that produced, on the surface of the youngest Pennsylvanian sediments, channels which were later filled with glacial till of lower density than the sediments. 13 figures.

Dana, S.W.

1980-03-01

176

DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia.  

PubMed

Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5. PMID:16827919

Chowdari, K V; Northup, A; Pless, L; Wood, J; Joo, Y H; Mirnics, K; Lewis, D A; Levitt, P R; Bacanu, S-A; Nimgaonkar, V L

2007-04-01

177

XRCC1 gene polymorphisms and breast cancer risk in different populations: A meta-analysis  

Microsoft Academic Search

We performed a meta-analysis to investigate the role of XRCC1 polymorphisms Arg194Trp, Arg280His and Arg399Gln in breast cancer. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10?465 cases and 10?888 controls at Arg194Trp, 6156

Huihua Li; Tam Cam Ha; Bee Choo Tai

2009-01-01

178

Variation in cancer risk estimates for exposure to powerline frequency electromagnetic fields: A meta-analysis comparing EMF measurement methods  

Microsoft Academic Search

We used meta-analysis to synthesize the findings from eleven case-control studies on cancer risks in humans exposed to 50-60 Hertz powerline electromagnetic fields (EMFs). Pooled estimates of risk are derived for different EMF measurement methods and types of cancer. EMF measurement methods are classified as: wiring configuration codes, distance to power distribution equipment, spot measurements of magnetic fields, and calculated

Michelle A. Miller; James R. Murphy; Thomas I Miller; A. J. Ruttenber

1995-01-01

179

Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis  

PubMed Central

Background Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association. Methods All studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Six studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT?/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis. Conclusions This meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT?/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069

2014-01-01

180

Occupational exposure to diesel exhaust and lung cancer: a meta-analysis.  

PubMed Central

OBJECTIVES: We undertook a meta-analysis of epidemiological studies investigating the relationship between occupational diesel exhaust exposure and lung cancer. METHODS: Thirty of 47 studies initially identified as potentially relevant met specified inclusion criteria. We extracted or calculated 39 independent estimates of relative risk and derived pooled estimates of risk for all studies and for numerous study subsets by using a random-effects model. We also examined interstudy heterogeneity by using linear metaregressions. RESULTS: There was substantial heterogeneity in the pooled risk estimates for all studies combined and for most subsets. Several factors consistent with higher study quality, however, contributed to increased pooled estimates of risk and lower heterogeneity, including (1) adjustment for confounding by cigarette smoking and other covariates, (2) having a lower likelihood of selection bias, and (3) having increased study power. CONCLUSION: This analysis provides quantitative support for prior qualitative reviews that have ascribed an etiologic role to occupational diesel exhaust exposure in lung cancer induction. Among study populations most likely to have had substantial exposure to diesel exhaust, the pooled smoking-adjusted relative risk was 1.47 (95% confidence interval = 1.29, 1.67).

Lipsett, M; Campleman, S

1999-01-01

181

MGMT Leu84Phe gene polymorphism and lung cancer risk: a meta-analysis.  

PubMed

Many studies have examined the association between the MGMT Leu84Phe polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95 % CI?=?0.97-1.21 P?=?0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95 % CI?=?0.99-1.21 P?=?0.445 for heterogeneity) and 1.46 (95 % CI?=?1.05-2.02 P?=?0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians. PMID:24390665

Qiu, Zhi-Xiong; Xue, Fei; Shi, Xuan-Feng; He, Xiao; Ma, Hui-Ni; Chen, Lan; Chen, Pin-Zhong

2014-05-01

182

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium  

PubMed Central

Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29?423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.

Vajdic, Claire M.; Falster, Michael; Engels, Eric A.; Martinez-Maza, Otoniel; Turner, Jennifer; Hjalgrim, Henrik; Vineis, Paolo; Seniori Costantini, Adele; Bracci, Paige M.; Holly, Elizabeth A.; Willett, Eleanor; Spinelli, John J.; La Vecchia, Carlo; Zheng, Tongzhang; Becker, Nikolaus; De Sanjose, Silvia; Chiu, Brian C.-H.; Dal Maso, Luigino; Cocco, Pierluigi; Maynadie, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Grulich, Andrew E.; Cozen, Wendy

2008-01-01

183

Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium  

PubMed Central

Lung cancer (LC) is the leading cause of cancer-related death worldwide and tobacco smoking is the major associated risk factor. DNA repair is an important process, maintaining genome integrity and polymorphisms in DNA repair genes may contribute to susceptibility to LC. To explore the role of DNA repair genes in LC, we conducted a multilevel association study with 1655 single nucleotide polymorphisms (SNPs) in 211 DNA repair genes using 6911 individuals pooled from four genome-wide case–control studies. Single SNP association corroborates previous reports of association with rs3131379, located on the gene MSH5 (P = 3.57 × 10-5) and returns a similar risk estimate. The effect of this SNP is modulated by histological subtype. On the log-additive scale, the odds ratio per allele is 1.04 (0.84–1.30) for adenocarcinomas, 1.52 (1.28–1.80) for squamous cell carcinomas and 1.31 (1.09–1.57) for other histologies (heterogeneity test: P = 9.1 × 10?3). Gene-based association analysis identifies three repair genes associated with LC (P < 0.01): UBE2N, structural maintenance of chromosomes 1L2 and POLB. Two additional genes (RAD52 and POLN) are borderline significant. Pathway-based association analysis identifies five repair pathways associated with LC (P < 0.01): chromatin structure, DNA polymerases, homologous recombination, genes involved in human diseases with sensitivity to DNA-damaging agents and Rad6 pathway and ubiquitination. This first international pooled analysis of a large dataset unravels the role of specific DNA repair pathways in LC and highlights the importance of accounting for gene and pathway effects when studying LC.

Kazma, Remi; Babron, Marie-Claude; Gaborieau, Valerie; Genin, Emmanuelle; Brennan, Paul; Hung, Rayjean J.; McLaughlin, John R.; Krokan, Hans E.; Elvestad, Maiken B.; Skorpen, Frank; Anderssen, Endre; Vooder, Tonu; Valk, Kristjan; Metspalu, Andres; Field, John K.; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

2012-01-01

184

Incorporating network structure in integrative analysis of cancer prognosis data.  

PubMed

In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate-to-strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance. PMID:23161517

Liu, Jin; Huang, Jian; Ma, Shuangge

2013-02-01

185

Analysis of IL-1 ? release from cryopreserved pooled lymphocytes in response to lipopolysaccharide and lipoteichoic acid.  

PubMed

Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1?, IL-6, and TNF-?. The present study was to analyze the influence of cryopreservation in IL-1? release, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTA in vitro. The inflammatory cytokine, IL-1? release, was measured by ELISA method. It was observed that the release of IL-1? increases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation. PMID:24024208

Nair, Sreelekshmi R; Geetha, C S; Mohanan, P V

2013-01-01

186

Analysis of IL-1? Release from Cryopreserved Pooled Lymphocytes in Response to Lipopolysaccharide and Lipoteichoic Acid  

PubMed Central

Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1?, IL-6, and TNF-?. The present study was to analyze the influence of cryopreservation in IL-1? release, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTA in vitro. The inflammatory cytokine, IL-1? release, was measured by ELISA method. It was observed that the release of IL-1? increases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation.

Nair, Sreelekshmi R.; Geetha, C. S.; Mohanan, P. V.

2013-01-01

187

Role of survivin as prognostic and clinicopathological marker in gastric cancer: a meta-analysis.  

PubMed

Survivin has been implicated as a potential prognostic marker in a wide range of malignant tumours. However, the prognostic impact of survivin in gastric cancer remains to be controversial and published data are sometimes heterogeneous. Thus, aim of this study was to review the literature by performing an electronical database search via PubMed and EMBASE to identify eligible studies that assessed the impact of survivin as prognostic marker and its association with clinicopathological variables. Database search until November 21st 2012 retrieved 20 studies comprising 2,695 gastric cancer patients that assessed expression of survivin by immunohistochemistry or RT-PCR analyses in gastric cancer specimens. Meta-analyses of clinicopathological variables revealed an association between the expression of survivin and the presence of lymph node metastases (pooled OR: 0.58; 95 % CI 0.35-0.96). In addition, a correlation between the expression of survivin and overall survival for patients with gastric cancer (pooled HR 1.93; 95 % CI 1.51-2.48) became evident. More importantly, we were able to exclude a severe heterogeneity (I(2) = 31 %) or publication bias for the survival analyses. Furthermore, one-way sensitivity analysis and subgroup analyses regarding the method used to detect survivin, the type of survival analysis, the study quality and whether information was provided regarding neoadjuvant therapy supported our initial results. In conclusion, this meta-analysis indicates the prognostic significance of survivin in patients with gastric cancer. PMID:23948878

Krieg, Andreas; Baseras, Billur; Tomczak, Monika; Verde, Pablo Emilio; Stoecklein, Nikolas Hendrik; Knoefel, Wolfram Trudo

2013-09-01

188

A systemic analysis on pemetrexed in treating patients with breast cancer.  

PubMed

Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. Conclusion: This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line. PMID:24969886

Wan, Fang; Chen, Xin; Dong, Li-Fan; Cheng, Yue-Hong; Long, Jing-Pei

2014-01-01

189

The Cancer Genome Atlas Pan-Cancer analysis project.  

PubMed

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

Weinstein, John N; Collisson, Eric A; Mills, Gordon B; Shaw, Kenna R Mills; Ozenberger, Brad A; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M

2013-10-01

190

Socioeconomic differences in lung cancer incidence: a systematic review and meta-analysis  

Microsoft Academic Search

Objective  To investigate the associations between various socioeconomic indicators and lung cancer incidence.\\u000a \\u000a \\u000a \\u000a Methods  We searched PubMed and EMBASE databases for studies on socioeconomic position (SEP) and lung cancer incidence published through\\u000a October 2007. Random-effect model was used to pool the risk estimates from the individual studies. We stratified the analysis\\u000a by adjustment strategy to investigate the influence of smoking on socioeconomic

Anna Sidorchuk; Emilie E. Agardh; Olatunde Aremu; Johan Hallqvist; Peter Allebeck; Tahereh Moradi

2009-01-01

191

Mediation by peer violence victimization of sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors: pooled youth risk behavior surveys.  

PubMed

Objectives. We examined the role of adolescent peer violence victimization (PVV) in sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors. Methods. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex sexual attraction, partners, or identity as sexual minority and the remainder as heterosexual. We had 4 indicators of tobacco and alcohol use and 4 of sexual risk and 2 PVV factors: victimization at school and carrying weapons. We stratified associations by gender and race/ethnicity. Results. PVV was related to disparities in cancer-related risk behaviors of substance use and sexual risk, with odds ratios (ORs) of 1.3 (95% confidence interval [CI]?=?1.03, 1.6) to 11.3 (95% CI?=?6.2, 20.8), and to being a sexual minority, with ORs of 1.4 (95% CI?=?1.1, 1.9) to 5.6 (95% CI?=?3.5, 8.9). PVV mediated sexual orientation disparities in substance use and sexual risk behaviors. Findings were pronounced for adolescent girls and Asian/Pacific Islanders. Conclusions. Interventions are needed to reduce PVV in schools as a way to reduce sexual orientation disparities in cancer risk across the life span. PMID:24825215

Rosario, Margaret; Corliss, Heather L; Everett, Bethany G; Russell, Stephen T; Buchting, Francisco O; Birkett, Michelle A

2014-06-01

192

Patient-level pooled analysis of adjudicated gastrointestinal outcomes in celecoxib clinical trials: meta-analysis of 51,000 patients enrolled in 52 randomized trials.  

PubMed

ABSTRACT: INTRODUCTION: Although the safety of celecoxib has been investigated, limited data are available on complications affecting the entire (upper and lower) gastrointestinal (GI) tract, with no patient-level pooled analyses of upper and lower GI outcomes available. We therefore evaluated the upper and lower GI safety of celecoxib by using patient-level data from randomized controlled trials (RCTs). METHODS: This patient-level pooled analysis included 52 prospective, randomized, double-blind parallel-group studies from the Celecoxib Clinical Database. Each study had a planned duration of continuous treatment with celecoxib or a nonselective nonsteroidal antiinflammatory drug (nsNSAID), rofecoxib, or the placebo comparator arm for at least 4 weeks. All studies with final reports completed by 1 October 2007 were included. The primary end point was the combined incidence of clinically significant upper and lower GI events (CSULGIEs). An independent blinded committee reviewed and adjudicated all end points by using predefined criteria and all available reported adverse events, laboratory data, and case narratives. All doses of celecoxib and all doses of all nsNSAIDs were pooled for analysis. RESULTS: The pooled analysis involved 51,048 patients; 28,614 were randomized to celecoxib; 15,278 to nsNSAIDs (including 3,248 patients taking naproxen, 2,640 taking ibuprofen, 8,066 taking diclofenac, 1,234 taking loxoprofen, and 90 taking ketoprofen); 5,827 to placebo and 1,329 to rofecoxib. The mean age was 60 years, and 65% were women. Data on 1,042 patients with potential GI events were reviewed for end-points adjudication; the adjudication committee confirmed 89 patients with CSULGIEs. The majority were in the celecoxib and nsNSAID groups (with raw incidence proportions of 37 (0.1%) and 40 (0.3%), respectively). The incidence rates were 0.3, 0.9 and 0.3 per 100 patient-years in the celecoxib, nsNSAID, and placebo groups, respectively. The time to incidence of CSULGIEs was significantly longer with celecoxib than with nsNSAIDs (P = 0.0004). CONCLUSIONS: When compared with nsNSAIDs, celecoxib is associated with a significantly lower risk of all clinically significant GI events throughout the entire GI tract. This pooled analysis of 52 RCTs significantly advances the understanding of the upper and lower GI safety profile of celecoxib and its potential benefits to patients. PMID:23298471

Moore, Andrew; Makinson, Geoffrey; Li, Chunming

2013-01-01

193

Analysis of dose rates received around the storage pool for irradiated control rods in a BWR nuclear power plant.  

PubMed

BWR control rods are activated by neutron reactions in the reactor. The dose produced by this activity can affect workers in the area surrounding the storage pool, where activated rods are stored. Monte Carlo (MC) models for neutron activation and dose assessment around the storage pool have been developed and validated. In this work, the MC models are applied to verify the expected reduction of dose when the irradiated control rod is hanged in an inverted position into the pool. PMID:21093278

Ródenas, J; Abarca, A; Gallardo, S

2011-08-01

194

Analysis of the dose rate produced by control rods discharged from a BWR into the irradiated fuel pool.  

PubMed

BWR control rods become activated by neutron reactions into the reactor. Therefore, when they are withdrawn from the reactor, they must be stored into the storage pool for irradiated fuel at a certain depth under water. Dose rates on the pool surface and the area surrounding the pool should be lower than limits for workers. The MCNP code based on the Monte Carlo method has been applied to model this situation and to calculate dose rates at points of interest. PMID:19836252

Ródenas, J; Gallardo, S; Abarca, A; Juan, V

2010-01-01

195

NaK pool-boiler bench-scale receiver durability test: Test results and materials analysis  

Microsoft Academic Search

Pool-boiler reflux receivers have been considered as an alternative to heat pipes for the input of concentrated solar energy to Stirling-cycle engines in dish-Stirling electric generation systems. Pool boilers offer simplicity in design and fabrication. The operation of a full-scale pool-boiler receiver has been demonstrated for short periods of time. However, to generate cost-effective electricity, the receiver must operate Without

C. E. Andraka; S. H. Goods; R. W. Bradshaw; J. B. Moreno; T. A. Moss; S. A. Jones

1994-01-01

196

Alert but less alarmed: a pooled analysis of terrorism threat perception in Australia  

PubMed Central

Background Previous Australian research has highlighted disparities in community perceptions of the threat posed by terrorism. A study with a large sample size is needed to examine reported concerns and anticipated responses of community sub-groups and to determine their consistency with existing Australian and international findings. Methods Representative samples of New South Wales (NSW) adults completed terrorism perception questions as part of computer assisted telephone interviews (CATI) in 2007 (N = 2081) and 2010 (N = 2038). Responses were weighted against the NSW population. Data sets from the two surveys were pooled and multivariate multilevel analyses conducted to identify health and socio-demographic factors associated with higher perceived risk of terrorism and evacuation response intentions, and to examine changes over time. Results In comparison with 2007, Australians in 2010 were significantly more likely to believe that a terrorist attack would occur in Australia (Adjusted Odd Ratios (AOR) = 1.24, 95%CI:1.06-1.45) but felt less concerned that they would be directly affected by such an incident (AOR = 0.65, 95%CI:0.55-0.75). Higher perceived risk of terrorism and related changes in living were associated with middle age, female gender, lower education and higher reported psychological distress. Australians of migrant background reported significantly lower likelihood of terrorism (AOR = 0.52, 95%CI:0.39-0.70) but significantly higher concern that they would be personally affected by such an incident (AOR = 1.57, 95%CI:1.21-2.04) and having made changes in the way they live due to this threat (AOR = 2.47, 95%CI:1.88-3.25). Willingness to evacuate homes and public places in response to potential incidents increased significantly between 2007 and 2010 (AOR = 1.53, 95%CI:1.33-1.76). Conclusion While an increased proportion of Australians believe that the national threat of terrorism remains high, concern about being personally affected has moderated and may reflect habituation to this threat. Key sub-groups remain disproportionately concerned, notably those with lower education and migrant groups. The dissonance observed in findings relating to Australians of migrant background appears to reflect wider socio-cultural concerns associated with this issue. Disparities in community concerns regarding terrorism-related threat require active policy consideration and specific initiatives to reduce the vulnerabilities of known risk groups, particularly in the aftermath of future incidents.

2011-01-01

197

Independent review of design and analysis for Holtec spent fuel storage racks of CPP 666 Pool 1  

SciTech Connect

This document summarizes the analyses and review performed to develop and validate the design of the new fuel storage racks for the Idaho Chemical Processing Plant (ICPP) Fuel Storage Area (FSA). Holtec International is responsible for the design and fabrication of the storage racks. This report describes the issues raised in the review effort and the resolutions to these issues. The conclusion is reached that the review issues for the racks of Pool 1 have been satisfactorily resolved in the final design and analysis for these racks. Section 1 of this report gives a brief description of the project. Section 2 describes the approach that Holtec used in analyzing the racks and results from these analyses. Section 3 describes the independent review process. Section 4 discusses the identification of and resolution to comments on the design analysis. Section 5 describes additional analysis performed to address major concerns with the Holtec design analysis. Section 6 presents a summary of AEC`s independent review, which is based on AEC`s final review report. Finally, Section 7 gives the Lockheed Idaho Technologies Company (LITCO) position on the acceptability of Holtec`s design.

Miller, G.K.

1996-03-01

198

Myeloperoxidase Polymorphism, Menopausal Status, and Breast Cancer Risk: An Update Meta-Analysis  

PubMed Central

Myeloperoxidase (MPO) is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian) for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR?=?0.56, 95% CI 0.34–0.94, p?=?0.027). Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR?=?0.57, 95% CI 0.34–0.93, p?=?0.025). We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women’s risk of developing breast cancer.

Peng, Qi-Liu; Huang, Xiu-Li; Mo, Cui-Ju; Li, Shan; Zhao, Jin-Min

2013-01-01

199

Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women  

PubMed Central

Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers. Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116?056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intake Results A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer. Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.

2013-01-01

200

Single cell analysis of cancer genomes.  

PubMed

Genomic studies have provided key insights into how cancers develop, evolve, metastasize and respond to treatment. Cancers result from an interplay between mutation, selection and clonal expansions. In solid tumours, this Darwinian competition between subclones is also influenced by topological factors. Recent advances have made it possible to study cancers at the single cell level. These methods represent important tools to dissect cancer evolution and provide the potential to considerably change both cancer research and clinical practice. Here we discuss state-of-the-art methods for the isolation of a single cell, whole-genome and whole-transcriptome amplification of the cell's nucleic acids, as well as microarray and massively parallel sequencing analysis of such amplification products. We discuss the strengths and the limitations of the techniques, and explore single-cell methodologies for future cancer research, as well as diagnosis and treatment of the disease. PMID:24531336

Van Loo, Peter; Voet, Thierry

2014-02-01

201

Association between Class III Obesity (BMI of 40-59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies  

PubMed Central

Background The prevalence of class III obesity (body mass index [BMI]?40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences?=?238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences?=?36.7 and 62.3 in men and women, respectively) and diabetes (rate differences?=?51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary

Kitahara, Cari M.; Flint, Alan J.; Berrington de Gonzalez, Amy; Bernstein, Leslie; Brotzman, Michelle; MacInnis, Robert J.; Moore, Steven C.; Robien, Kim; Rosenberg, Philip S.; Singh, Pramil N.; Weiderpass, Elisabete; Adami, Hans Olov; Anton-Culver, Hoda; Ballard-Barbash, Rachel; Buring, Julie E.; Freedman, D. Michal; Fraser, Gary E.; Beane Freeman, Laura E.; Gapstur, Susan M.; Gaziano, John Michael; Giles, Graham G.; Hakansson, Niclas; Hoppin, Jane A.; Hu, Frank B.; Koenig, Karen; Linet, Martha S.; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Schairer, Catherine; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Hartge, Patricia

2014-01-01

202

Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis  

PubMed Central

Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. Study registration This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

Cohen, Stephen M; Vogel, Jon D; Marcet, Jorge E; Candiotti, Keith A

2014-01-01

203

Outcomes in Ethnic Minority Renal Transplant Recipients Receiving Everolimus versus Mycophenolate: Comparative Risk Assessment Results From a Pooled Analysis  

PubMed Central

Background Everolimus (EVR) has demonstrated good efficacy after renal transplantation. Racial disparities in clinical outcomes after de novo renal transplantation are well documented; whether the efficacy of EVR varies based on recipient ethnicity is unknown. We conducted a comparative risk assessment of EVR by ethnicity. Methods Data on 2004 renal transplant recipients from three EVR studies were pooled to identify the impact of ethnicity on efficacy outcomes across EVR dosing groups and control groups. Ethnic groups compared were African Americans, non-U.S. blacks, Asians, Hispanics, and Caucasians. EVR groups received either 1.5 or 3 mg per day, with either standard-dose cyclosporine or reduced-dose cyclosporine. Control groups received mycophenolic acid (MPA) with standard-dose cyclosporine. Composite efficacy failure endpoint was graft loss, death, biopsy-proven acute rejection, or lost to follow-up. Adjusted odds ratios were calculated using a logistic regression model. Results The proportion of renal transplant recipients who met the composite endpoint was African Americans (46%), non-U.S. black (35%), Caucasian (31%), Hispanic (28%), and Asian (25%). The odds of meeting the composite endpoint were significantly (P=0.0001) greater for African Americans versus Caucasians but did not differ among the other ethnic groups (ethnic groups were only compared with Caucasians). EVR and MPA were associated with similar efficacy among each of the ethnic groups. Conclusion In this pooled data analysis in more than 2000 renal transplant recipients, EVR versus MPA resulted in similar composite endpoint incidence events across ethnicities. Consistent with previously published data, African Americans had poorer clinical outcomes. EVR is efficacious regardless of ethnicity.

Melancon, Keith; Mulgaonkar, Shamkant P.; Delcoro, Carlos; Wiland, Anne; McCague, Kevin; Shihab, Fuad S.

2013-01-01

204

Therapeutic Response to Vasoconstrictors in Hepatorenal Syndrome Parallels Increase in Mean Arterial Pressure: A Pooled Analysis of Clinical Trials  

PubMed Central

Background Vasoconstrictor therapy has been advocated as treatment for hepatorenal syndrome (HRS). Our aim was to explore whether across all tested vasoconstrictors, achievement of a substantial rise in arterial blood pressure is associated with recovery of kidney function in HRS. Study Design Pooled analysis of published studies identified by electronic database search. Setting & Population Data pooled across 501 subjects from 21 studies. Selection Criteria for Studies Human studies evaluating the efficacy of a vasoconstrictor administered for ? 72 hours in adults with HRS Type 1 or 2. Intervention Vasoconstrictor therapy. Outcomes & Measurements Cohorts’ mean arterial pressure (MAP), serum creatinine, urinary output and plasma renin activity (PRA) at baseline and at subsequent time points during treatment. Linear regression models were constructed to estimate the mean daily change in MAP, serum creatinine, urinary output and PRA for each study subgroup. Correlations were used to assess for association between variables. Results An increase in MAP is strongly associated with a decline in serum creatinine but not associated with an increase in urinary output. The associations were stronger when analyses were restricted to randomized clinical trials and were not limited to cohorts with either lower baseline MAP or lower baseline serum creatinine. The majority of the studies tested terlipressin as vasoconstrictor, whereas fewer studies tested ornipressin, midodrine, octreotide or norepinephrine. Excluding cohorts of subjects treated with terlipressin or ornipressin did not eliminate the association. Furthermore, a fall in PRA correlated with improvement in kidney function. Limitations Studies were not originally designed to test our question. We lacked access to individual patient data. Conclusions A rise in MAP during vasoconstrictor therapy in HRS is associated with improvement in kidney function, across the spectrum of drugs tested to date. These results support consideration for a goal-directed approach to the treatment of HRS.

Velez, Juan Carlos Q.; Nietert, Paul J.

2011-01-01

205

Meta-analysis of cancer gene expression signatures reveals new cancer genes, SAGE tags and tumor associated regions of co-regulation  

PubMed Central

Cancer is among the major causes of human death and its mechanism(s) are not fully understood. We applied a novel meta-analysis approach to multiple sets of merged serial analysis of gene expression and microarray cancer data in order to analyze transcriptome alterations in human cancer. Our methodology, which we denote ‘COgnate Gene Expression patterNing in tumours’ (COGENT), unmasked numerous genes that were differentially expressed in multiple cancers. COGENT detected well-known tumor-associated (TA) genes such as TP53, EGFR and VEGF, as well as many multi-cancer, but not-yet-tumor-associated genes. In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues. Furthermore, a significant number of RIDGEs are associated with GC-rich regions on the genome. All assembled data is freely available online (www.oncoreveal.org) as a tool implementing COGENT analysis of multi-cancer genes and RIDGEs. These findings engender a deeper understanding of cancer biology by demonstrating the existence of a pool of under-studied multi-cancer genes and by highlighting the cancer-specificity of some TA-RIDGEs.

Kavak, Ersen; Unlu, Mustafa; Nister, Monica; Koman, Ahmet

2010-01-01

206

Meta-analysis of cancer gene expression signatures reveals new cancer genes, SAGE tags and tumor associated regions of co-regulation.  

PubMed

Cancer is among the major causes of human death and its mechanism(s) are not fully understood. We applied a novel meta-analysis approach to multiple sets of merged serial analysis of gene expression and microarray cancer data in order to analyze transcriptome alterations in human cancer. Our methodology, which we denote 'COgnate Gene Expression patterNing in tumours' (COGENT), unmasked numerous genes that were differentially expressed in multiple cancers. COGENT detected well-known tumor-associated (TA) genes such as TP53, EGFR and VEGF, as well as many multi-cancer, but not-yet-tumor-associated genes. In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues. Furthermore, a significant number of RIDGEs are associated with GC-rich regions on the genome. All assembled data is freely available online (www.oncoreveal.org) as a tool implementing COGENT analysis of multi-cancer genes and RIDGEs. These findings engender a deeper understanding of cancer biology by demonstrating the existence of a pool of under-studied multi-cancer genes and by highlighting the cancer-specificity of some TA-RIDGEs. PMID:20621981

Kavak, Ersen; Unlü, Mustafa; Nistér, Monica; Koman, Ahmet

2010-11-01

207

Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials  

PubMed Central

Background The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy. Methods Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ?2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated. Results HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death. Conclusion HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202

2013-01-01

208

A new approach to characterize populations of Schistosoma mansoni from humans: development and assessment of microsatellite analysis of pooled miracidia  

PubMed Central

Summary OBJECTIVES To develop and assess a microsatellite technique to characterize populations of Schistosoma mansoni from humans. METHODS For each of five patients, we calculated the allele count and frequency at 11 loci for several pools of miracidia (50 and 100), and compared these to population values, determined by amplifying microsatellites from 186 to 200 individual miracidia per patient. RESULTS We were able to detect up to 94.5% of alleles in pools. Allele count and frequency strongly and significantly correlated between singles and pools; marginally significant differences (P < 0.05) were detected for one patient (pools of 50) for allele frequencies and for two patients (pools of 100) for allele counts. Kato–Katz egg counts and number of alleles per pool did not co-vary, indicating that further direct comparisons of the results from these two techniques are needed. CONCLUSIONS Allele counts and frequency profiles from pooling provide important information about infection intensity and complexity, beyond that obtained from traditional methods. Although we are not advocating use of pooling to replace individual genotyping studies, it can potentially be useful in certain applications as a rapid and cost effective screening method for studies of S. mansoni population genetics, or as a more informative way to quantify and characterize human worm populations.

Hanelt, B.; Steinauer, M. L.; Mwangi, I. N.; Maina, G. M.; Agola, L. E.; Mkoji, G. M.; Loker, E. S.

2010-01-01

209

Root and Shoot Respiration of Perennial Ryegrass Are Supplied by the Same Substrate Pools: Assessment by Dynamic 13C Labeling and Compartmental Analysis of Tracer Kinetics1[OA  

PubMed Central

The substrate supply system for respiration of the shoot and root of perennial ryegrass (Lolium perenne) was characterized in terms of component pools and the pools' functional properties: size, half-life, and contribution to respiration of the root and shoot. These investigations were performed with perennial ryegrass growing in constant conditions with continuous light. Plants were labeled with 13CO2/12CO2 for periods ranging from 1 to 600 h, followed by measurements of the rates and 13C/12C ratios of CO2 respired by shoots and roots in the dark. Label appearance in roots was delayed by approximately 1 h relative to shoots; otherwise, the tracer time course was very similar in both organs. Compartmental analysis of respiratory tracer kinetics indicated that, in both organs, three pools supplied 95% of all respired carbon (a very slow pool whose kinetics could not be characterized provided the remaining 5%). The pools' half-lives and relative sizes were also nearly identical in shoot and root (half-life < 15 min, approximately 3 h, and 33 h). An important role of short-term storage in supplying respiration was apparent in both organs: only 43% of respiration was supplied by current photosynthate (fixed carbon transferred directly to centers of respiration via the two fastest pools). The residence time of carbon in the respiratory supply system was practically the same in shoot and root. From this and other evidence, we argue that both organs were supplied by the same pools and that the residence time was controlled by the shoot via current photosynthate and storage deposition/mobilization fluxes.

Lehmeier, Christoph Andreas; Lattanzi, Fernando Alfredo; Schaufele, Rudi; Wild, Melanie; Schnyder, Hans

2008-01-01

210

Modelling and experimental analysis of the role of interacting cytosolic and vacuolar pools in shaping low temperature calcium signatures in plant cells.  

PubMed

A major challenge to understanding low temperature calcium signatures in plants is defining how these signatures emerge from the interactions of different molecular components that are stored in different subcellular pools of a plant cell. Here we develop an integrative model that incorporates the interactions of Ca²?, H?, K?, Cl? and ATP in both cytosolic and vacuolar pools. Our analysis reveals how these four major ions along with ATP forms a complex network to relate the emergence of calcium signatures to other responses (e.g. pH response). Modelling results are in agreement with experimental observations for both cytosolic free calcium concentration ([Ca²?](c)) and pH. The model is further validated by experimentally measuring the response of [Ca²?](c) to six fluctuating (rather than constant) temperature profiles. We found that modelling results are in reasonable agreement with experimental observations, in particular, if the rate of reducing temperature is relatively high. In addition, we show that both calcium-induced calcium release (CICR) at the vacuolar membrane and transport of ions from the cytosolic pool to the vacuolar membrane play important roles in the interaction between cytosolic and vacuolar pools. In combination they control the amount and timing of calcium release from the vacuolar to cytosolic pool, shaping the specific calcium signature. The methodology and principles developed here establish an integrative view on the role of cytosolic and vacuolar pools in shaping calcium signatures in general, and they are universally applicable to study of the interactions of multiple subcellular pools. PMID:22722805

Liu, Junli; Knight, Heather; Hurst, Charlotte H; Knight, Marc R

2012-08-01

211

Risk factors of breast cancer: a systematic review and meta-analysis.  

PubMed

The etiology of breast cancer might be explained by 2 mechanisms, namely, differentiation and proliferation of breast epithelial cells mediated by hormonal factors. We performed a systematic review and meta-analysis to update effects of risk factors for both mechanisms. MEDLINE and EMBASE were searched up to January 2011. Studies that assessed association between oral contraceptives (OC), hormonal replacement therapy (HRT), diabetes mellitus (DM), or breastfeeding and breast cancer were eligible. Relative risks with their confidence intervals (CIs) were extracted. A random-effects method was applied for pooling the effect size. The pooled odds ratios of OC, HRT, and DM were 1.10 (95% CI = 1.03-1.18), 1.23 (95% CI = 1.21-1.25), and 1.14 (95% CI = 1.09-1.19), respectively, whereas the pooled odds ratio of ever-breastfeeding was 0.72 (95% CI = 0.58-0.89). Our study suggests that OC, HRT, and DM might increase risks, whereas breastfeeding might lower risks of breast cancer. PMID:23709491

Anothaisintawee, Thunyarat; Wiratkapun, Cholatip; Lerdsitthichai, Panuwat; Kasamesup, Vijj; Wongwaisayawan, Sansanee; Srinakarin, Jiraporn; Hirunpat, Siriporn; Woodtichartpreecha, Piyanoot; Boonlikit, Sarawan; Teerawattananon, Yot; Thakkinstian, Ammarin

2013-09-01

212

Pooling Data from Multiple Longitudinal Studies: The Role of Item Response Theory in Integrative Data Analysis  

ERIC Educational Resources Information Center

There are a number of significant challenges researchers encounter when studying development over an extended period of time, including subject attrition, the changing of measurement structures across groups and developmental periods, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies…

Curran, Patrick J.; Hussong, Andrea M.; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J.; Zucker, Robert A.

2008-01-01

213

Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations  

SciTech Connect

Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years) and 51 showed Be-sensitization without lung granulomas detected by trans-bronchial biopsy (ag

Cesare Saltini, Massimo Amicosante

2009-12-19

214

Glycomic Analysis of Prostate Cancer.  

National Technical Information Service (NTIS)

In this proposal, we are testing the hypothesis that the risk of developing prostate cancer and the aggressiveness of the disease are influenced by protein glycosylation. We postulate that glycobiology contributes to the higher susceptibility of African A...

R. Goldman

2011-01-01

215

Glycomic Analysis of Prostate Cancer.  

National Technical Information Service (NTIS)

In this proposal, we are testing the hypothesis that the risk of developing prostate cancer and the aggressiveness of the disease are influenced by protein glycosylation. We postulate that glycobiology contributes to the higher susceptibility of African A...

R. Goldman

2010-01-01

216

Breast cancer histopathology image analysis: a review.  

PubMed

This paper presents an overview of methods that have been proposed for the analysis of breast cancer histopathology images. This research area has become particularly relevant with the advent of whole slide imaging (WSI) scanners, which can perform cost-effective and high-throughput histopathology slide digitization, and which aim at replacing the optical microscope as the primary tool used by pathologist. Breast cancer is the most prevalent form of cancers among women, and image analysis methods that target this disease have a huge potential to reduce the workload in a typical pathology lab and to improve the quality of the interpretation. This paper is meant as an introduction for nonexperts. It starts with an overview of the tissue preparation, staining and slide digitization processes followed by a discussion of the different image processing techniques and applications, ranging from analysis of tissue staining to computer-aided diagnosis, and prognosis of breast cancer patients. PMID:24759275

Veta, Mitko; Pluim, Josien P W; van Diest, Paul J; Viergever, Max A

2014-05-01

217

Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma.  

PubMed

Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM. PMID:18838334

Betti, Marta; Neri, Monica; Ferrante, Daniela; Landi, Stefano; Biava, Alessandra; Gemignani, Federica; Bertolotti, Marinella; Mirabelli, Dario; Padoan, Marina; Ugolini, Donatella; Botta, Mario; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

2009-05-01

218

Analysis with Data Mining and Ant Colony Algorithm for Implementing of Object Pool Optimization  

Microsoft Academic Search

In essence, the goal of data mining is to extract knowledge from data. Data mining is an inter-disciplinary field, whose core is at the intersection of machine learning, statistics and databases.J2ME services play an important role in the field of Communication industry. In this paper, we discuss and analyze the consumptive behaviour and a detailed analysis of Ant Colony Algorithm

Farha Haneef; Ganesh Raj Kushwaha; Ashutosh K. Dubey

2011-01-01

219

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials  

PubMed Central

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.

Tao, Haitao; Cheng, Yao; Han, Lu; Li, Xiaoyan; Hu, Yi

2013-01-01

220

Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma.  

PubMed

Harmine hydrochloride (Har-hc), a derivative from Harmine which is a natural extractive from plants, has been considered for treatment of kinds of cancers and cerebral diseases. In this study, we found that Har-hc clearly decreased cell viability, induced apoptosis and inhibited Akt phosphorylation in glioblastoma cell lines. Moreover, Har-hc had the ability to inhibit self-renewal and promote differentiation of glioblastoma stem like cells (GSLCs) accompanied by inhibition of Akt phosphorylation. Especially, we demonstrated that Har-hc inhibited neurosphere formation of human primary GSLCs. In vivo test also confirmed Har-hc decreased the tumorigenicity of GSLCs. Thus we conclude that Har-hc has potent anti-cancer effects in glioblastoma cells, which is at least partially via inhibition of Akt phosphorylation. Administration of Har-hc may act as a new approach to glioblastoma treatment. PMID:23392846

Liu, Huailei; Han, Dayong; Liu, Yaohua; Hou, Xu; Wu, Jianing; Li, Huadong; Yang, Jie; Shen, Chen; Yang, Guang; Fu, Changyu; Li, Xianfeng; Che, Hui; Ai, Jing; Zhao, Shiguang

2013-03-01

221

SPECT gated blood pool phase analysis of lateral wall motion for prediction of CRT response.  

PubMed

Amplitude, defined as the magnitude of contraction of the myocardium, is obtained from phase analysis but has not been investigated to the same extent as phase-based parameters for predicting the outcome of cardiac resynchronization therapy (CRT). The size of scar present in the lateral wall of the left ventricle (LV) has been shown in some studies to predict response to CRT. Scar is associated with impaired regional LV wall motion and is expected to result in a reduction in the corresponding amplitude values derived from phase analysis. Our objective was to determine the correlation between amplitude and scar, and to evaluate amplitude parameters as surrogates for scar in predicting response to CRT. 49 patients underwent a single photon emission computed tomography (SPECT) radionuclide angiography (RNA) scan as well as FDG viability and Rubidium-82 perfusion PET scans prior to undergoing CRT. Phase analysis was performed on the SPECT RNA data to extract amplitude values used to define amplitude size (AmpSize) and amplitude score (AmpScore) parameters. Scar size and scar score were obtained from the PET scans based on a 5 segment model. Scar parameters were then compared to amplitude parameters in the lateral wall for the whole population as well as both ischemic (N = 27) and non-ischemic (N = 22) populations using Pearson correlation. The ability of amplitude parameters to predict response to CRT was also investigated and compared to scar parameters. The largest ROC AUC values were obtained in the ischemic population where values of 0.67 and 0.68 were observed for lateral wall AmpSize and AmpScore respectively. Both parameters produced the same sensitivity and specificity values of 83 and 67 %. Amplitude size in the lateral wall showed significant correlation with lateral wall scar size in all patients (r = 0.51), which was further strengthened in the ischemic patient sub-group (r = 0.64). Lateral wall amplitude-based parameters obtained from SPECT RNA phase analysis produced an overall accuracy in predicting CRT response in ischemic patients that was not significantly different to that of PET lateral wall scar parameters. A significant correlation existed between amplitude size and scar size in the lateral wall. PMID:24402886

Lalonde, Michel; Birnie, David; Ruddy, Terrence D; deKemp, Robert A; Beanlands, Rob S B; Wassenaar, Richard; Wells, R Glenn

2014-03-01

222

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer  

PubMed Central

Background With less than a 5% survival rate pancreatic adenocarcinoma (PDAC) is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. Methods and Findings We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. Conclusions Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic pancreatic adenocarcinoma.

Crnogorac-Jurcevic, Tatjana; Chelala, Claude; Barry, Sayka; Harada, Tomohiko; Bhakta, Vipul; Lattimore, Sam; Jurcevic, Stipo; Bronner, Mary; Lemoine, Nicholas R.; Brentnall, Teresa A.

2013-01-01

223

[Analysis of microsatellite alteration in colorectal cancer].  

PubMed

We investigated the possible correlation between the microsatellite alterations (replication error: RER, and loss of heterozygosity: LOH) and clinicopathologic factors and survival in colorectal cancer. A total of 78 colorectal cancers was examined for microsatellite alteration at three microsatellite loci containing D2S123, D18S58 and C117-703. RER is considered positive when at least one microsatellite locus is detected. RER was positive in 28.2%, and the respective positivity was 12.8%, 15.3% and 11.5%. The positivity of LOH was 6.4%, 10.3% and 19.2%, in that order. RER-positive cancers were more significantly found in the proximal colon than the distal colorectum. Node-negative colorectal cancers were more noted in RER (+)-positive cancers. Multivariate analysis showed that LOH in D18S58 locus and RER in CI17-703 locus were independent prognostic factors. PMID:9589050

Mizunuma, H; Takita, K; Ooki, S; Onda, M; Ando, Y; Yoshida, T; Tsuchiya, A; Abe, R

1998-04-01

224

Seismic analysis of a large pool-type LMR (liquid metal reactor)  

SciTech Connect

This paper describes the seismic study of a 450-MWe liquid metal reactor (LMR) under 0.3-g SSE ground excitation. Two calculations were performed using the new design configuration. They deal with the seismic response of the reactor vessel, the guard vessel and support skirt, respectively. In both calculations, the stress and displacement fields at important locations of those components are investigated. Assessments are also made on the elastic and inelastic structural capabilities for other beyond-design basis seismic loads. Results of the reactor vessel analysis reveal that the maximum equivalent stress is only about half of the material yield stress. For the guard vessel and support skirt, the stress level is very small. Regarding the analysis if inelastic structural capability, solutions of the Newmark-Hall ductility modification method show that the reactor vessel can withstand seismics with ground ZPAs ranging from 1.015 to 1.31 g, which corresponds to 3.37 to 4.37 times the basic 0.3-g SSE. Thus, the reactor vessel and guard vessel are strong enough to resist seismic loads. 4 refs., 10 figs., 5 tabs.

Wang, C.Y.; Gvildys, J.

1989-01-01

225

Meta-Analysis of ABCB1 3435C>T Polymorphism and Colorectal Cancer  

PubMed Central

Objective: Many studies have focused on the association between the ABCB1 3435C>T polymorphism and colorectal cancer (CRC) risk. However, the results were conflicting. The aim of this meta-analysis is to evaluate the precise association between this polymorphism and CRC risk. Methods: We formally reviewed the literature at Pubmed, EMBASE and the Cochrane Library with the key words as follows: ABCB1/MDR1/P-glycoprotein, polymorphism, colorectal and cancer/neoplasm/tumor. This meta-analysis was assessed by Review manager 5.0. The fixed-effects model was used to pool the odds ratios (OR) with 95% confidence intervals (CI) for CRC risk. Results: There were 8 studies identified. The pooled OR with 95% CI of CC+CT versus TT genotype of the ABCB1 3435C>T polymorphism for CRC risk was 1.01 [0.90-1.13]. The sensitivity analysis further confirmed the result. Heterogeneity and publication bias were not observed in this meta-analysis. Conclusions: In summary, there was no significant association between the ABCB1 3435C>T polymorphism and CRC risk. Abbreviations used: the ATP-binding cassette, subfamily B, member 1 (ABCB1); multidrug resistance gene 1 (MDR1); P-glycoprotein (P-gp); colorectal cancer (CRC); single nucleotide polymorphisms (SNPs); odds ratio (OR); confidence interval (CI); Hardy-Weinberg equilibrium (HWE).

Zhang, Dan; Wang, Cun; Zhou, Zongguang

2013-01-01

226

Flux Imbalance Analysis and the Sensitivity of Cellular Growth to Changes in Metabolite Pools  

PubMed Central

Stoichiometric models of metabolism, such as flux balance analysis (FBA), are classically applied to predicting steady state rates - or fluxes - of metabolic reactions in genome-scale metabolic networks. Here we revisit the central assumption of FBA, i.e. that intracellular metabolites are at steady state, and show that deviations from flux balance (i.e. flux imbalances) are informative of some features of in vivo metabolite concentrations. Mathematically, the sensitivity of FBA to these flux imbalances is captured by a native feature of linear optimization, the dual problem, and its corresponding variables, known as shadow prices. First, using recently published data on chemostat growth of Saccharomyces cerevisae under different nutrient limitations, we show that shadow prices anticorrelate with experimentally measured degrees of growth limitation of intracellular metabolites. We next hypothesize that metabolites which are limiting for growth (and thus have very negative shadow price) cannot vary dramatically in an uncontrolled way, and must respond rapidly to perturbations. Using a collection of published datasets monitoring the time-dependent metabolomic response of Escherichia coli to carbon and nitrogen perturbations, we test this hypothesis and find that metabolites with negative shadow price indeed show lower temporal variation following a perturbation than metabolites with zero shadow price. Finally, we illustrate the broader applicability of flux imbalance analysis to other constraint-based methods. In particular, we explore the biological significance of shadow prices in a constraint-based method for integrating gene expression data with a stoichiometric model. In this case, shadow prices point to metabolites that should rise or drop in concentration in order to increase consistency between flux predictions and gene expression data. In general, these results suggest that the sensitivity of metabolic optima to violations of the steady state constraints carries biologically significant information on the processes that control intracellular metabolites in the cell.

Reznik, Ed; Mehta, Pankaj; Segre, Daniel

2013-01-01

227

Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies  

PubMed Central

Purpose Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point. Methods We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis. Results Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96–1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07–1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72–1.02) or cohort studies (OR?=?1.01, 95% CI?=?0.91–1.13). Conclusions The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association.

Tian, Shu-bo; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin; Cao, Zhan-jiang

2014-01-01

228

Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis.  

PubMed

Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation. PMID:24058201

Minicocci, Ilenia; Santini, Sara; Cantisani, Vito; Stitziel, Nathan; Kathiresan, Sekar; Arroyo, Juan Antonio; Martí, Gertrudis; Pisciotta, Livia; Noto, Davide; Cefalù, Angelo B; Maranghi, Marianna; Labbadia, Giancarlo; Pigna, Giovanni; Pannozzo, Fabio; Ceci, Fabrizio; Ciociola, Ester; Bertolini, Stefano; Calandra, Sebastiano; Tarugi, Patrizia; Averna, Maurizio; Arca, Marcello

2013-12-01

229

Virtual pools for interactive analysis and software development through an integrated Cloud environment  

NASA Astrophysics Data System (ADS)

WNoDeS, an acronym for Worker Nodes on Demand Service, is software developed at CNAF-Tier1, the National Computing Centre of the Italian Institute for Nuclear Physics (INFN) located in Bologna. WNoDeS provides on demand, integrated access to both Grid and Cloud resources through virtualization technologies. Besides the traditional use of computing resources in batch mode, users need to have interactive and local access to a number of systems. WNoDeS can dynamically select these computers instantiating Virtual Machines, according to the requirements (computing, storage and network resources) of users through either the Open Cloud Computing Interface API, or through a web console. An interactive use is usually limited to activities in user space, i.e. where the machine configuration is not modified. In some other instances the activity concerns development and testing of services and thus implies the modification of the system configuration (and, therefore, root-access to the resource). The former use case is a simple extension of the WNoDeS approach, where the resource is provided in interactive mode. The latter implies saving the virtual image at the end of each user session so that it can be presented to the user at subsequent requests. This work describes how the LHC experiments at INFN-Bologna are testing and making use of these dynamically created ad-hoc machines via WNoDeS to support flexible, interactive analysis and software development at the INFN Tier-1 Computing Centre.

Grandi, C.; Italiano, A.; Salomoni, D.; Calabrese Melcarne, A. K.

2011-12-01

230

The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta-analysis.  

PubMed

Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk. The present study was aimed to evaluate the association of these two variants with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A, nine reports including 6,765 CRC patients and 8,496 unrelated controls were identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC with the pooled OR was 1.12 (95% CI = 1.02-1.23), and the pooled OR for the homozygotes *6A/*6A was 1.13 (95% CI = 0.80-1.58) compared to the homozygotes *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03-1.23, *6A/*6A and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case-control studies with 1,074 cases and 1,945 controls were found. Although no significant association was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97, 95% CI = 0.67-1.42), the homozygosity A/A carriers showed a significant elevated risk of CRC (pooled OR = 1.68, 95% CI = 1.14-2.47) compared to G/G homozygotes. Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI = 1.17-2.51). These data strongly suggested that the two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of CRC risk. PMID:21858550

Zhang, Xueli; Wu, Liang; Sheng, Youhua; Zhou, Wenhua; Huang, Zhongming; Qu, Jun; Gao, Ganglong; Cai, Duan; Zhang, Ming

2012-03-01

231

Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies  

PubMed Central

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APO?4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10?11) and APO?2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10?15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10?5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond?2 and ?4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

2011-01-01

232

Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis.  

PubMed

The previous published data on the association between TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. 38 publications with 51 studies were selected for this meta-analysis, including 17,337 cases and 16,127 controls for TP53 codon 72 (from 43 studies), 2,201 cases and 2,399 controls for TP53 intron 6 (from four studies), and 4,322 cases and 4,558 controls for TP53 intron 3 16 bp (from four studies). When all the eligible studies were pooled into the meta-analysis of codon 72 polymorphism, there was significant association between lung cancer risk and codon 72 polymorphism in any genetic model (dominant model: OR = 1.13, 95 % CI 1.05-1.21; recessive model: OR = 1.14, 95 % CI 1.02-1.27; additive model: OR = 1.19, 95 % CI 1.05-1.33). In the subgroup analysis by ethnicity, histological type, source of control, and smoking status, significantly increased risks were observed in subgroups such as Asians, Caucasians, lung squamous cell carcinoma patients for Asians, population-based study, hospital-based study, non-smokers, and smokers. When all the eligible studies were pooled into the meta-analysis of intron 6 polymorphism, there was significant association between lung cancer risk and intron 6 polymorphism in dominant model (OR = 1.27, 95 % CI 1.11-1.44). When all the eligible studies were pooled into the meta-analysis of intron 3 16 bp polymorphism, there was significant association between lung cancer risk and intron 3 16 bp polymorphism in dominant model (OR = 1.12, 95 % CI 1.02-1.23) and additive model (OR = 1.41, 95 % CI 1.04-1.90). Additionally, when one study was deleted in the sensitive analysis, the results of TP53 intron 3 16 bp duplication polymorphism were changed in the dominant model (OR = 1.11, 95 % CI 0.87-1.42) and additive model (OR = 1.01, 95 % CI 0.65-1.56). In summary, this meta-analysis indicates that codon 72 and intron 6 polymorphisms show an increased lung cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk. PMID:24271138

Ye, Xiang-Hua; Bu, Zhi-Bin; Feng, Jie; Peng, Ling; Liao, Xin-Biao; Zhu, Xin-Li; Sun, Xiao-Li; Yu, Hao-Gang; Yan, Dan-Fang; Yan, Sen-Xiang

2014-01-01

233

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients.  

PubMed

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

Barta, Stefan K; Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y; Mounier, Nicolas; Kaplan, Lawrence D; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C; Noy, Ariela; Sparano, Joseph A

2013-11-01

234

Do deficits in cardiac care influence high mortality rates in schizophrenia? A systematic review and pooled analysis  

PubMed Central

We have previously documented inequalities in the quality of medical care provided to those with mental ill health but the implications for mortality are unclear. We aimed to test whether disparities in medical treatment of cardiovascular conditions, specifically receipt of medical procedures and receipt of prescribed medication, are linked with elevated rates of mortality in people with schizophrenia and severe mental illness. We undertook a systematic review of studies that examined medical procedures and a pooled analysis of prescribed medication in those with and without comorbid mental illness, focusing on those which recruited individuals with schizophrenia and measured mortality as an outcome. From 17 studies of treatment adequacy in cardiovascular conditions, eight examined cardiac procedures and nine examined adequacy of prescribed cardiac medication. Six of eight studies examining the adequacy of cardiac procedures found lower than average provision of medical care and two studies found no difference. Meta-analytic pooling of nine medication studies showed lower than average rates of prescribing evident for the following individual classes of medication; angiotensin converting enzyme inhibitors (n?=?6, aOR?=?0.779, 95% CI?=?0.638–0.950, p?=?0.0137), beta-blockers (n?=?9, aOR?=?0.844, 95% CI?=?0.690–1.03, p?=?0.1036) and statins (n?=?5, aOR?=?0.604, 95% CI?=?0.408–0.89, p?=?0.0117). No inequality was evident for aspirin (n?=?7, aOR?=?0.986, 95% CI?=?0.7955–1.02, p?=?0.382). Interestingly higher than expected prescribing was found for older non-statin cholesterol-lowering agents (n?=?4, aOR?=?1.55, 95% CI?=?1.04–2.32, p?=?0.0312). A search for outcomes in this sample revealed ten studies linking poor quality of care and possible effects on mortality in specialist settings. In half of the studies there was significantly higher mortality in those with mental ill health compared with controls but there was inadequate data to confirm a causative link. Nevertheless, indirect evidence supports the observation that deficits in quality of care are contributing to higher than expected mortality in those with severe mental illness (SMI) and schizophrenia. The quality of medical treatment provided to those with cardiac conditions and comorbid schizophrenia is often suboptimal and may be linked with avoidable excess mortality. Every effort should be made to deliver high-quality medical care to people with severe mental illness.

Mitchell, Alex J; Lord, Oliver

2010-01-01

235

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies  

PubMed Central

Background Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; pnoninferiority?cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy. Conclusion The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups. Trial registration EINSTEIN-PE: ClinicalTrials.gov, NCT00439777; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193.

2013-01-01

236

Effect of telmisartan vs. ramipril on 'dipping' status and blood pressure variability: pooled analysis of the PRISMA studies.  

PubMed

A retrospective pooled analysis of the 'Prospective, Randomized Investigation of the Safety and Efficacy of MICARDIS vs. Ramipril Using ABPM' studies conducted in Europe and South Africa (PRISMA I) and in the United States of America and Canada (PRISMA II) was carried out to investigate the effects of telmisartan and ramipril on dipper status (extreme dippers, dippers, non-dippers, risers/reverse dippers), and blood pressure (BP) variability in 1279 patients (with normal sleeping patterns and valid 24-h ambulatory BP monitoring recordings at baseline and end point). After 14 weeks' treatment, telmisartan had a greater systolic BP (SBP) reduction and higher smoothness index in all four dipper groups compared with ramipril. In addition, the tendency toward dipping was significantly higher in patients treated with) telmisartan than ramipril (P=0.032; odds ratio for telmisartan vs. ramipril: 1.27 (95% confidence interval: 1.102-1.58)). In patients with an early morning SBP surge ?35?mm?Hg, telmisartan treatment was associated with significantly greater reductions from baseline in the night-time low mean, early morning mean and early morning SBP surge compared with ramipril (P=0.026, P<0.0001 and P=0.0006, respectively). In this retrospective analysis, telmisartan was shown to normalize the circadian BP pattern to a dipper profile in a larger proportion of patients than ramipril, and reduce early-morning SBP surge in high-risk patients, indicative of a cardioprotective effect. These findings need to be confirmed in long-term prospective trials and observational studies. PMID:24048485

Gosse, Philippe; Schumacher, Helmut

2014-02-01

237

Analysis of haloacetic acids in water and air (aerosols) from indoor swimming pools using HS-SPME/GC/ECD.  

PubMed

A solid phase microextraction method was used for the analysis of nine haloacetic acids (HAAs) in water and air (aerosols) from indoor swimming pools (ISPs). The analysis is characterized by derivatization of HAAs to their methyl-esters with dimethyl sulphate, headspace solid phase microextraction (HS-SPME) with a Carboxen-polydimethylsiloxane (CAR-PDMS) fiber and gas chromatography - electron capture detector (GC/ECD). High correlation coefficients were obtained for esters mixture calibration lines and detection limits were found to be at the low ppb level. Repeatability was assessed and coefficients of variation varied from 10 to 20%. Reproducibility was also evaluated and coefficients of variation from 15 to 25% were obtained. Analytical results from four Portuguese ISPs showed that the mean concentration of total HAAs (THAAs) in water ranged from 10 ± 2 to 183 ± 28 ?g/L in which 55 ± 20% corresponded to trichloroacetic and dichloroacetic acids (TCAA and DCAA). THAAs highest concentrations were directly related to higher ISPs' water organic matter content. In the lack of European specific regulation for water from ISPs and taking into consideration that ingestion is a form of exposure, THAAs concentration values were compared with drinking water maximum contamination level (MCL) of 60 ?g/L proposed by the US EPA for the sum of five HAAs. In 35% of water sampling campaigns the sum of MBAA (monobromoacetic acid), MCAA (monochloroacetic acid), DCAA and TCAA exceeded that MCL value. The concentrations obtained for THAAs in the ISPs' atmosphere ranged from 5 ± 1 to 64 ± 10 ?g/m(3) (T = 28°C at 5 cm above the water surface) and were proportional to the aerosols' quantity, which was deeply related to indoor air ventilation system. PMID:22242869

Sá, Christopher S A; Boaventura, Rui A R; Pereira, Isabel B

2012-01-01

238

The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis  

PubMed Central

Background: The prognostic value of CDKN2A promoter hypermethylation in colorectal cancer remains controversial. We systematically reviewed the evidence for assessment of CDKN2A methylation in colorectal cancer to elucidate this issue. Methods: Pubmed, Embase and ISI web of knowledge were searched to identify eligible studies to evaluate the association of CDKN2A hypermethylation and overall survival and clinicopathological features of colorectal cancer patients. Combined hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were pooled using a random-effects model. Results: A total of 11 studies encompassing 3440 patients were included in the meta-analysis. CDKN2A hypermethylation had an unfavourable impact on OS of patients with colorectal cancer (HR 1.65, 95% CI 1.29–2.11). Subgroup analysis indicated that CDKN2A hypermethylation was significantly correlated with OS in Europe (HR 1.49; 95% CI 1.28–1.74) and Asia (HR 3.30; 95% CI 1.68–6.46). Furthermore, there was a significant association between CDKN2A hypermethylation and lymphovascular invasion (OR 1.68, 95% CI 1.15–2.47), lymph node metastasis (OR 1.68, 95% CI 1.09–2.59) and proximal tumour location (OR 2.09, 95% CI 1.34–3.26) of colorectal cancer. Conclusion: This meta-analysis indicated that CDKN2A hypermethylation might be a predictive factor for unfavourable prognosis of colorectal cancer patients.

Xing, X; Cai, W; Shi, H; Wang, Y; Li, M; Jiao, J; Chen, M

2013-01-01

239

Vitamin A and risk of bladder cancer: a meta-analysis of epidemiological studies  

PubMed Central

Background Epidemiological studies have reported the preventive effect of vitamin A intake on bladder cancer. However, the findings are inconsistent. To address this issue we conducted a meta-analysis to investigate the quantitative effects of vitamin A on bladder cancer. Methods We searched MEDLINE and Embase databases and the references of the relevant articles in English to include studies on dietary or blood vitamin A for the risk of bladder cancer. We performed a meta-analysis using both fixed-effects and random-effects models. Results Twenty-five articles on dietary vitamin A or blood vitamin A were included according to the eligibility criteria. The pooled risk estimates of bladder cancer were 0.82 (95% CI 0.65, 0.95) for total vitamin A intake, 0.88 (95% CI 0.73, 1.02) for retinol intake, and 0.64 (95% CI 0.38, 0.90) for blood retinol levels. We also found inverse associations between subtypes of carotenoids and bladder cancer risk. Conclusion The findings of this meta-analysis indicate that high vitamin A intake was associated with a lower risk of bladder cancer. Larger studies with prospective design and rigorous methodology should be considered to validate the current findings.

2014-01-01

240

Prognostic Significance of Lymphovascular Invasion in Radical Cystectomy on Patients with Bladder Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Purpose The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI) in radical cystectomy specimens. Materials and Methods Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. Results A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26–2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38–2.01), and overall survival (pooled HR, 1.67; 95% CI, 1.38–2.01), despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. Conclusions This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.

Kim, Hwanik; Kim, Myong; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

2014-01-01

241

Meta-analysis in cancer genetics.  

PubMed

Genetic association studies report potentially conflicting findings which meta-analysis seeks to quantify and objectively summarize. Attributing cancer to a single gene variant requires large sample sizes, which may strain resources in a primary study. Properly used, meta-analysis is a powerful tool for resolving discrepancies in genetic association studies given the exponential increase in sample sizes when data are combined. The several steps involved in this methodology require careful attention to critical issues in meta-analysis, heterogeneity and publication bias, evaluation of which can be graphical or statistical. Overall summary effects of a meta-analysis may or may not reflect similar associations when the component studies are sub grouped. Overall associations and that of the subgroups are evaluated for tenability using sensitivity analysis. The low association between a polymorphism and cancer is offset by detectable changes in cancer incidence in the general population making them an important issue from a public health point of view. Asian meta-analytic publications in cancer genetics come from six countries with an output that number from one to two. The exception is China, whose publication output has increased exponentially since 2008. PMID:20593927

Pabalan, Noel A

2010-01-01

242

The Role of Adiponectin in Breast Cancer: A Meta-Analysis  

PubMed Central

Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.

Liu, Li-Yuan; Wang, Meng; Ma, Zhong-Bing; Yu, Li-Xiang; Zhang, Qiang; Gao, De-Zong; Wang, Fei; Yu, Zhi-Gang

2013-01-01

243

Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis  

Microsoft Academic Search

Individual-based studies that investigated the relation between dietary alpha-linolenic acid (ALA) intake and prostate cancer\\u000a risk have shown inconsistent results. We carried out a meta-analysis of prospective studies to examine this association. We\\u000a systematically searched studies published up to December 2008. Log relative risks (RRs) were weighted by the inverse of their\\u000a variances to obtain a pooled estimate with its

Marion Carayol; Pascale Grosclaude; Cyrille Delpierre

2010-01-01

244

Efficacy and safety of unfractionated heparin versus enoxaparin: a pooled analysis of ASSENT-3 and -3 PLUS data  

PubMed Central

Background The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. Methods We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. Results The primary efficacy end point, a composite of 30-day mortality, reinfarction or refractory ischemia, was 16.0% with enoxaparin versus 12.2% with unfractionated heparin (p < 0.001); the efficacy plus safety (intracranial hemorrhage [ICH] or major systemic bleeding) end point, 18.0% versus 15.0% (p = 0.003). The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. Interpretation These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.

Armstrong, Paul W.; Chang, Wei-Ching; Wallentin, Lars; Goldstein, Patrick; Granger, Christopher B.; Bogaerts, Kris; Danays, Thierry; Van de Werf, Frans

2006-01-01

245

Incidence of adverse events with telmisartan compared with ACE inhibitors: evidence from a pooled analysis of clinical trials  

PubMed Central

Telmisartan is indicated for the prevention of cardiovascular events in high-risk patients, based on comparable efficacy to the angiotensin-converting enzyme (ACE) inhibitor, ramipril, in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®) trial. However, tolerability must be considered when selecting treatments. This analysis compared the tolerability of telmisartan and ACE inhibitors using data pooled from 12 comparative, randomized studies involving 2564 telmisartan-treated patients and 2144 receiving ACE inhibitors (enalapril, lisinopril, or ramipril). Incidence rates of adverse events for the combined ACE inhibitor treatments and for telmisartan were similar (42.8% vs 43.9%, respectively) as were the rates of serious adverse events (1.8% vs 1.7% for telmisartan, respectively). Patients receiving ACE inhibitors had more cough (8.6% vs 2.6% with telmisartan, P < 0.0001). Results were similar irrespective of age, gender, or ethnicity. The adverse event of angioedema was observed in four patients (0.2%) receiving ACE inhibitors versus none with telmisartan (P = 0.043). There were small, numerical differences in serious adverse events. A total of 107 patients (5.0%) receiving ACE inhibitors and 93 patients (3.6%) receiving telmisartan discontinued treatment because of adverse events (P = 0.021); of these, 32.7% and 5.4%, respectively, were discontinuations due to cough (relative risk reduction of 88% [P < 0.0001] with telmisartan). Telmisartan and ACE inhibitors produced comparable blood pressure reductions at marketed doses. Telmisartan and ACE inhibitors are suitable for the prevention of cardiovascular events in high-risk patients, but telmisartan is better tolerated, particularly with regard to cough.

Mancia, Giuseppe; Schumacher, Helmut

2012-01-01

246

Analysis of loss-of-flow transients in a pool-type LMFBR using SSC-P  

SciTech Connect

In order to have a general analytical capability for the safety evaluation of any proposed LMFBR system, the USNRC is sponsoring the development and validation of computer codes for both pool- and loop-type plants. The computer code for pool-type LMFBRs is designated SSC-P. This paper is concerned with the application of SSC-P to simulate loss-of-flow accident transients in a pool-type LMFBR. The models required for dynamic plant simulation are briefly highlighted. The system response is calculated for (1) a complete loss of electric power event, with scram, leading the plant into buoyancy-induced natural circulation, (2) a protected pipe rupture accident in the primary pump discharge line, and (3) an unprotected loss of off-site power event. For the last case, the predicted results from SSC-P are compared with the published results of Phenix behavior by NOVATOME.

Madni, I.K.; Cazzoli, E.G.

1982-01-01

247

Pathway-based analysis of breast cancer  

PubMed Central

Introduction: Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer. Methods: 13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array. Results: Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways. Conclusions: There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs.

Song, Dong; Cui, Miao; Zhao, Gang; Fan, Zhimin; Nolan, Katherine; Yang, Ying; Lee, Peng; Ye, Fei; Zhang, David Y

2014-01-01

248

Association between PTEN Gene IVS4 Polymorphism and Risk of Cancer: A Meta-Analysis  

PubMed Central

Background Phosphatase and tensin homolog (PTEN) is a well established tumor suppressor gene. Recently, increasing studies investigated the association between PTEN IVS4 polymorphism (rs3830675) and risk of various types of cancer. However, the results from the individual studies were controversial. The aim of this meta-analysis was to elucidate whether PTEN IVS4 polymorphism was associated with cancer risk. Methods Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to assess the strength of association between PTEN IVS4 polymorphism and cancer risk. Results A total of seven case-control studies were finally included in this meta-analysis. The pooled analysis suggested that individuals with PTEN IVS4 (?/?) genotype were significantly associated with increased risk of cancer (OR?=?1.45, 95% CI?=?1.19–1.76, P<0.001) and subgroup of digestive tract cancer (OR?=?1.67, 95% CI?=?1.28–2.18, P<0.001) compared with (+/+) genotype. The allele analysis revealed that (?) allele was significantly associated with increased risk of cancer (OR?=?1.30, 95% CI?=?1.12–1.50, P?=?0.001) and subgroup of digestive tract cancer (OR?=?1.42, 95% CI?=?1.16–1.74, P?=?0.001) compared with (+) allele. No significant association was observed between PTEN IVS4 (+/?) genotype and risk of cancer. Conclusion PTEN IVS4 (?/?) genotype was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+/+) genotype. The (?) allele of PTEN IVS4 (rs3830675) polymorphism was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+) allele. The recessive effect model and dominant effect model also demonstrated significant association between PTEN IVS4 (rs3830675) polymorphism and increased cancer risk especially for digestive tract cancer. Further large-scale and well-designed studies regarding different ethnicities are still required to confirm the results of our meta-analysis.

Sun, Liping; Liu, Jingwei; Yuan, Quan; Xing, Chengzhong; Yuan, Yuan

2014-01-01

249

Pharmacological evidence for the existence of multiple functional pools of brain serotonin: analysis of brain perfusate from conscious rats.  

PubMed

The serotonin reuptake inhibitor fluoxetine significantly reduced levels of endogenous 5-hydroxyindoleacetic acid (5-HIAA) in brain perfusate of rats implanted with push-pull cannulas. This occurred in conjunction with its suppressant effect upon fixed-ratio operant behavior. Behavior suppressed with the serotonin agonist lysergic acid diethylamide (LSD) occurred in conjunction with a reduction of 5-HIAA only after 5-HIAA was elevated, shortly before, by 5 mg/kg of the serotonin precursor 5-hydroxytryptophan. Our data demonstrate the likely existence of multiple functional pools of serotonin in brain and support the notion that LSD preferentially affects a newly synthesized pool of this transmitter. PMID:6194257

Kleven, M S; Dwoskin, L P; Sparber, S B

1983-10-01

250

Quantitative Measurement of Bromoform in Swimming Pool Water Using SPME with GC-MS. An Undergraduate Instrumental Analysis Experiment  

NASA Astrophysics Data System (ADS)

A senior-level undergraduate laboratory experiment that demonstrates the use of solid-phase microextraction (SPME) and capillary gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative determination of bromoform in swimming pool water. Bromoform was extracted by SPME from the headspace of vials containing sodium chloride-saturated swimming pool water. Bromoform concentrations were determined from comparisons of peak areas on a student-generated calibration curve. Students compared results to OSHA water and air exposure limits for bromoform.

Hardee, John R.; Long, John; Otts, Julie

2002-05-01

251

Content analysis of cancer blog posts*  

PubMed Central

Objectives: The efficacy of user-defined subject tagging and software-generated subject tagging for describing and organizing cancer blog contents was explored. Methods: The Technorati search engine was used to search the blogosphere for cancer blog postings generated during a two-month period. Postings were mined for relevant subject concepts, and blogger-defined tags and Text Analysis Portal for Research (TAPoR) software–defined tags were generated for each message. Descriptive data were collected, and the blogger-defined tags were compared with software-generated tags. Three standard vocabularies (Opinion Templates, Basic Resource, and Medical Subject Headings [MeSH] Resource) were used to assign subject terms to the blogs, with results compared for efficacy in information retrieval. Results: Descriptive data showed that most of the studied cancer blogs (80%) contained fewer than 500 words each. The numbers of blogger-defined tags per posting (M?=?4.49 per posting) were significantly smaller than the TAPoR keywords (M?=?23.55 per posting). Both blogger-defined subject tags and software-generated subject tags were often overly broad or overly narrow in focus, producing less than effective search results for those seeking to extract information from cancer blogs. Conclusions: Additional exploration into methods for systematically organizing cancer blog postings is necessary if blogs are to become stable and efficacious information resources for cancer patients, friends, families, or providers.

Kim, Sujin

2009-01-01

252

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis  

PubMed Central

Background Many published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of this relationship. Methods A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. Results Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T) and XbaI (A>G) polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T) polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C), codon 325 (C>G), codon 594 (G>A) and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed. Conclusion Results from the current meta-analysis indicate that ESR1 PvuII (C>T) polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may increase the risk of prostate cancer among American population.

Wang, Yu-Mei; Liu, Zu-Wang; Guo, Jing-Bo; Wang, Xiao-Fang; Zhao, Xin-Xin; Zheng, Xuan

2013-01-01

253

Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs  

Microsoft Academic Search

BACKGROUND: Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon. METHODS: A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups

Hong Liu-Seifert; David H Adams; Bruce J Kinon

2005-01-01

254

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes  

Microsoft Academic Search

BACKGROUND: In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to

Debora Williams-Herman; Samuel S Engel; Elizabeth Round; Jeremy Johnson; Gregory T Golm; Hua Guo; Bret J Musser; Michael J Davies; Keith D Kaufman; Barry J Goldstein

2010-01-01

255

Can statins reduce risk of lung cancer, especially among elderly people? A meta-analysis  

PubMed Central

Objective As the most common cause of cancer mortality throughout the world, lung cancer has drawn people’s attention on how to reduce the risk with chemopreventive ways. Many epidemiological studies have shown inconsistent effects of statins on lung cancer, but some observational studies have showed that statins had protective effect on lung cancer among elderly people. So we preformed this meta-analysis to find whether statins were chemopreventive. Methods We searched MEDLINE, EMBASE and Web of Science databases from inception to September, 2013. A total of 23 studies were selected, including 15 observational studies and 8 randomized controlled trials (RCTs). Both fixed and random-effects models were used to calculate pooled estimates in primary and sensitivity analyses. We used Q and I2 statistics to assess statistical heterogeneity, and evaluated publication bias by Begg’s test and Egger’s test. Results No association between statins and lung cancer risk was identified either in the meta-analysis among RCTs [relative risk (RR): 0.95, 95% confidence interval (95% CI): 0.85-1.06] or observational studies (RR: 0.89, 95% CI: 0.77-1.04). We also selected 6 observational studies that all researched on elderly people. The result of meta-analysis showed that there was still no protective effect between statins and lung cancer among elderly people (RR: 1.03, 95% CI: 0.96-1.11). Conclusions Our results did not support a protective effect of statins on the overall lung cancer risk and the lung cancer risk among elderly people. More well-designed RCTs are needed to enhance our understanding of the chemopreventive effect of statins on lung cancer.

Deng, Zhantao; Zhang, Shu; Yi, Long

2013-01-01

256

Pooled genetic analysis in ultrasound measured non-alcoholic fatty liver disease in Indian subjects: A pilot study  

PubMed Central

AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease (NAFLD) by performing a pooled genetic study. METHODS: Study subjects (n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty (n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association studies done to date on NAFLD were identified, 19 single nucleotide polymorphisms (SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student’s t test for continuous variables and ?2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was done. RESULTS The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 cms respectively. The mean triglyceride and alanine transaminase (ALT) levels in the control and NAFLD groups were 135.18 ± 7.77 mg/dL; 25.39 ± 14.73 IU/L and 184.40 ± 84.31 mg/dL; 110.20 ± 67.05 IU/L respectively. When ?2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3 (PNPLA3) gene (P = 0.001), rs2073080 of the PARVB gene (P = 0.02), rs2143571 of SAMM50 gene (P = 0.05) and rs6487679 of the pregnancy zone protein (PZP) gene (P = 0.01) with the disease. Variant single nucleotide polymorphisms (SNPs) in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4B and COL13A1 were associated with high triglyceride levels. Apart from the above associations, rs2073080, rs343062 and rs6591182 were significantly associated with high BMI; rs2854117 and rs738409 with high triglyceride levels; and rs2073080, rs2143571, rs2228603, rs6487679 and rs738409 with high ALT levels. CONCLUSION: Pooled genetic analysis revealed an association of SNPs in PNPLA3, PARVB, SAMM50 and PZP genes with NAFLD. SNPs in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4B and COL13A1 were associated with high triglyceride levels.

Kanth, Vishnubhotla Venkata Ravi; Sasikala, Mitnala; Rao, Padaki Nagaraja; Steffie Avanthi, Urmila; Rao, Kalashikam Rajender; Nageshwar Reddy, Duvvuru

2014-01-01

257

Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis  

PubMed Central

Background: Patients with type 2 diabetes have a 40% increased risk of bladder cancer. Thiazolidinediones, especially pioglitazone, may increase the risk. We conducted a systematic review and meta-analysis to evaluate the risk of bladder cancer among adults with type 2 diabetes taking thiazolidinediones. Methods: We searched key biomedical databases (including MEDLINE, Embase and Scopus) and sources of grey literature from inception through March 2012 for published and unpublished studies, without language restrictions. We included randomized controlled trials (RCTs), cohort studies and case–control studies that reported incident bladder cancer among people with type 2 diabetes who ever (v. never) were exposed to pioglitazone (main outcome), rosiglitazone or any thiazolidinedione. Results: Of the 1787 studies identified, we selected 4 RCTs, 5 cohort studies and 1 case–control study. The total number of patients was 2 657 365, of whom 3643 had newly diagnosed bladder cancer, for an overall incidence of 53.1 per 100 000 person-years. The one RCT that reported on pioglitazone use found no significant association with bladder cancer (risk ratio [RR] 2.36, 95% confidence interval [CI] 0.91–6.13). The cohort studies of thiazolidinediones (pooled RR 1.15, 95% CI 1.04–1.26; I2 = 0%) and of pioglitazone specifically (pooled RR 1.22, 95% CI 1.07–1.39; I2 = 0%) showed significant associations with bladder cancer. No significant association with bladder cancer was observed in the two RCTs that evaluated rosiglitazone use (pooled RR 0.87, 95% CI 0.34–2.23; I2 = 0%). Interpretation: The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes.

Colmers, Isabelle N.; Bowker, Samantha L.; Majumdar, Sumit R.; Johnson, Jeffrey A.

2012-01-01

258

Association of Mild to Moderate Chronic Kidney Disease with Venous Thromboembolism: Pooled Analysis of Five Prospective General Population Cohorts  

PubMed Central

Background Recent findings suggest that chronic kidney disease (CKD) may be associated with increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results We pooled individual participant data from five community-based cohorts from Europe (HUNT2, PREVEND and Tromsø study) and United States (ARIC and CHS study) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria and CKD with objectively verified VTE. To estimate adjusted hazard ratios (HRs) for VTE, categorical and continuous spline models were fit using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1,178 VTE events occurred over 599,453 person-years follow-up. Relative to eGFR 100 mL/min/1.73m2, HRs for VTE were 1.29 (95%CI, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for 60, 1.82 (1.27-2.60) for 45 and 1.95 (1.26-3.01) for 30 mL/min/1.73m2. Compared with albumin-creatinine ratio (ACR) of 5.0 mg/g, the HRs for VTE were 1.34 (1.04-1.72) for 30 mg/g, 1.60 (1.08-2.36) for 300 mg/g and 1.92 (1.19-3.09) for 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted HR for CKD defined as eGFR <60 mL/min/1.73m2 or albuminuria ?30 mg/g (vs. no CKD) was 1.54 (95%CI, 1.15-2.06). Associations were consistent in subgroups according to age, gender, and comorbidities as well as for unprovoked versus provoked VTE. Conclusions Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Naess, Inger Anne; Lutsey, Pamela L.; Braekkan, Sigrid K.; Veeger, Nic J. G. M.; Brodin, Ellen E.; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I.; Hammerstr?m, Jens; Cannegieter, Suzanne C.; Astor, Brad C.; Coresh, Josef; Folsom, Aaron R.; Hansen, John-Bjarne; Cushman, Mary

2012-01-01

259

PoolHap: Inferring Haplotype Frequencies from Pooled Samples by Next Generation Sequencing  

Microsoft Academic Search

With the advance of next-generation sequencing (NGS) technologies, increasingly ambitious applications are becoming feasible. A particularly powerful one is the sequencing of polymorphic, pooled samples. The pool can be naturally occurring, as in the case of multiple pathogen strains in a blood sample, multiple types of cells in a cancerous tissue sample, or multiple isoforms of mRNA in a cell.

Quan Long; Daniel C. Jeffares; Qingrun Zhang; Kai Ye; Viktoria Nizhynska; Zemin Ning; Chris Tyler-Smith; Magnus Nordborg; Thomas Mailund

2011-01-01

260

Duration, Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts  

Microsoft Academic Search

Background: Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified. Methodology and Principal Findings: Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were

Renaud Becquet; Ruth Bland; Valériane Leroy; Nigel C. Rollins; Didier K. Ekouevi; Anna Coutsoudis; François Dabis; Hoosen M. Coovadia; Roger Salamon; Marie-Louise Newell

2009-01-01

261

Uncertainty analysis of suppression pool heating during an ATWS in a BWR-5 plant. An application of the CSAU methodology using the BNL engineering plant analyzer  

SciTech Connect

The uncertainty has been estimated of predicting the peak temperature in the suppression pool of a BWR power plant, which undergoes an NRC-postulated Anticipated Transient Without Scram (ATWS). The ATWS is initiated by recirculation-pump trips, and then leads to power and flow oscillations as they had occurred at the LaSalle-2 Power Station in March of 1988. After limit-cycle oscillations have been established, the turbines are tripped, but without MSIV closure, allowing steam discharge through the turbine bypass into the condenser. Postulated operator actions, namely to lower the reactor vessel pressure and the level elevation in the downcomer, are simulated by a robot model which accounts for operator uncertainty. All balance of plant and control systems modeling uncertainties were part of the statistical uncertainty analysis that was patterned after the Code Scaling, Applicability and Uncertainty (CSAU) evaluation methodology. The analysis showed that the predicted suppression-pool peak temperature of 329.3 K (133{degrees}F) has a 95-percentile uncertainty of 14.4 K (26{degrees}F), and that the size of this uncertainty bracket is dominated by the experimental uncertainty of measuring Safety and Relief Valve mass flow rates under critical-flow conditions. The analysis showed also that the probability of exceeding the suppression-pool temperature limit of 352.6 K (175{degrees}F) is most likely zero (it is estimated as < 5-104). The square root of the sum of the squares of all the computed peak pool temperatures is 350.7 K (171.6{degrees}F).

Wulff, W.; Cheng, H.S.; Mallen, A.N. [Brookhaven National Lab., Upton, NY (United States); Johnsen, G.W. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Lellouche, G.S. [Technical Data Services, Chicago, IL (United States)

1994-03-01

262

Proteomic analysis of phosphorylation in cancer.  

PubMed

Constitutive activity of kinases is known to be crucial for a tumor to maintain its malignant phenotype, a phenomenon which is often referred to as oncogene addiction. The in-depth analysis of aberrant signaling pathways by the analysis of protein phosphorylation has become feasible through recent advances in proteomics technology. In this article we will review developments in the field of phosphoproteomics and its application in cancer research. The most widely used technologies for the generic enrichment of phosphopeptides are discussed as well as targeted approaches for the analysis of a specific subset of phosphopeptides. Validation experiments of phosphorylation sites using targeted mass spectrometry are also explained. Finally, we will highlight applications of phosphoproteomic technology in cancer research using cell lines and tissue. PMID:24666026

Ruprecht, Benjamin; Lemeer, Simone

2014-06-01

263

Networks in proteomics analysis of cancer.  

PubMed

Proteomics provides direct biological information on proteins but is still a limited platform. Borrowing from genomics, its cancer-specific applications can be broadly categorized as (1) pure diagnostics, (2) biomarkers, (3) identification of root causes and (4) identification of cancer-specific network rewirings. Biological networks capture complex relationships between proteins and provide an appropriate means of contextualization. While playing significantly larger roles, especially in 1 and 3, progress in proteomics-specific network-based methods is lagging as compared to genomics. Rapid hardware advances and improvements in proteomic identification and quantification have given rise to much better quality data alongside advent of new network-based analysis methods. However, a tighter integration between analytics and hardware is still essential for network analysis to play more significant roles in proteomics analysis. PMID:23481377

Goh, Wilson Wen Bin; Wong, Limsoon

2013-12-01

264

MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis  

PubMed Central

Objective The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and endometrial cancer risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. Methods All studies published up to August 2013 on the association between MDM2 SNP309 polymorphism and endometrial cancer risk were identified by searching electronic databases PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM). The association between the MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Eight case–control studies with 2069 endometrial cancer cases and 4546 controls were identified. Overall, significant increase of endometrial cancer risk was found when all studies were pooled in the meta-analysis (GG vs. TT: OR?=?1.464, 95% CI 1.246–1.721, P?analysis by ethnicity and HWE in controls, significant increase of endometrial cancer risks were observed in Caucasians and studies consistent with HWE. In subgroup analysis according to study quality, significant associations were observed in both high quality studies and low quality studies. Conclusions This meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility, especially in Caucasian populations. Further large and well-designed studies are needed to confirm this association.

2013-01-01

265

Methylomics analysis identifies epigenetically silenced genes and implies an activation of ?-catenin signaling in cervical cancer.  

PubMed

Using DNA methylation biomarkers in cancer detection is a potential direction in clinical testing. Some methylated genes have been proposed for cervical cancer detection; however, more reliable methylation markers are needed. To identify new hypermethylated genes in the discovery phase, we compared the methylome between a pool of DNA from normal cervical epithelium (n?=?19) and a pool of DNA from cervical cancer tissues (n?=?38) using a methylation bead array. We integrated the differentially methylated genes with public gene expression databases, which resulted in 91 candidate genes. Based on gene expression after demethylation treatment in cell lines, we confirmed 61 genes for further validation. In the validation phase, quantitative MSP and bisulfite pyrosequencing were used to examine their methylation level in an independent set of clinical samples. Fourteen genes, including ADRA1D, AJAP1, COL6A2, EDN3, EPO, HS3ST2, MAGI2, POU4F3, PTGDR, SOX8, SOX17, ST6GAL2, SYT9, and ZNF614, were significantly hypermethylated in CIN3+ lesions. The sensitivity, specificity, and accuracy of POU4F3 for detecting CIN3+ lesions were 0.88, 0.82, and 0.85, respectively. A bioinformatics function analysis revealed that AJAP1, EDN3, EPO, MAGI2, and SOX17 were potentially implicated in ?-catenin signaling, suggesting the epigenetic dysregulation of this signaling pathway during cervical cancer development. The concurrent methylation of multiple genes in cancers and in subsets of precancerous lesions suggests the presence of a driver of methylation phenotype in cervical carcinogenesis. Further validation of these new genes as biomarkers for cervical cancer screening in a larger population-based study is warranted. PMID:24310984

Chen, Yu-Chih; Huang, Rui-Lan; Huang, Yung-Kai; Liao, Yu-Ping; Su, Po-Hsuan; Wang, Hui-Chen; Chang, Cheng-Chang; Lin, Ya-Wen; Yu, Mu-Hsien; Chu, Tang-Yuan; Lai, Hung-Cheng

2014-07-01

266

RDA Analysis of Breast Cancer  

Cancer.gov

Dr. Michael Wigler, of Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, has been examining genetic changes in breast tumor tissue from patients on Long Island using a technique called representational difference analysis (RDA). In this pilot study, he demonstrated that the technique permits cloning of DNA probes that mark the presence of genetic lesions in tumors.

267

Differential impact of cilostazol on restenosis according to implanted stent type (from a pooled analysis of three DECLARE randomized trials).  

PubMed

Even in the drug-eluting stent era, restenosis has remained an unresolved issue, particularly in the treatment of complex coronary lesions. In this study, patient-level data from 3 randomized trials (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus [DECLARE-DIABETES] and Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Long Native Coronary Lesions [DECLARE-LONG] I and II) were pooled to estimate the differential antirestenotic efficacy of add-on cilostazol according to the implanted drug-eluting stent in patients at high risk for restenosis. A total of 1,399 patients underwent sirolimus-eluting stent (SES; n = 450), paclitaxel-eluting stent (n = 450), and zotarolimus-eluting stent (n = 499) implantation and received triple-antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol, n = 700) and dual-antiplatelet therapy (aspirin and clopidogrel, n = 699). Randomization of antiplatelet regimen was stratified by stent type. In-stent late loss after TAT was significantly lower than that after dual-antiplatelet therapy, regardless of implanted stent type. However, the incidence of in-segment restenosis after TAT was significantly lower with SES (0.5% vs 6.7%, p = 0.014) and zotarolimus-eluting stent (12.2% vs 20.0%, p = 0.028) implantation but not paclitaxel-eluting stent implantation (14.4% vs 20.0%, p = 0.244). A significant interaction was present between stent type and antiplatelet regimen for the risk for in-segment restenosis (p = 0.004). Post hoc analysis using bootstrap resampling methods showed that the relative risk reduction for in-segment restenosis after TAT was most prominent with SES implantation. In conclusion, add-on cilostazol effectively reduced restenosis in patients at high risk for restenosis, particularly in those receiving SES, suggesting the sustainable utility of add-on cilostazol therapy in newer generation drug-eluting stents with comparable efficacy with that of SES. PMID:23890573

Lee, Seung-Whan; Ahn, Jung-Min; Han, Seungbong; Park, Gyung-Min; Cho, Young-Rak; Lee, Woo-Seok; Jang, Jeong-Yoon; Kwon, Chang-Hee; Lee, Jong-Young; Kim, Won-Jang; Kang, Soo-Jin; Kim, Young-Hak; Lee, Cheol-Whan; Kim, Jae-Joong; Park, Seong-Wook; Park, Seung-Jung

2013-11-01

268

Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled Analysis of Phase 3 Study Results.  

PubMed

Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed for treating type 2 diabetes mellitus (T2DM). Methods: The safety/tolerability profile of canagliflozin 100 and 300 mg over 26 weeks was assessed using an integrated analysis of data pooled from 4 placebo-controlled, phase 3 studies representing a broad range of patients with T2DM (N = 2313; mean age, 56.0 years; glycated hemoglobin [HbA1c], 8.0%; body mass index, 32.1 kg/m2; estimated glomerular filtration rate, 88.1 mL/min/1.73 m2) on various prespecified background diabetes mellitus treatments. Safety/tolerability evaluations included adverse event (AE) reporting, with additional data collection prespecified for selected AEs, and assessments of renal-related, lipid, and other safety laboratory parameters. Trial Registration: ClinicalTrials.gov, NCT01081834; NCT01106625; NCT01106677; NCT01106690. Results: The overall incidence of AEs was similar with canagliflozin 100 and 300 mg and placebo; incidences of serious AEs and AEs leading to study discontinuation were low across groups. Canagliflozin was associated with higher incidences than placebo of genital mycotic infections and osmotic diuresis-related AEs; these were generally considered by the investigator to be mild to moderate in intensity and infrequently led to discontinuation. Canagliflozin was associated with transient reductions in estimated glomerular filtration rate that trended toward baseline over the assessment period; incidences of renal-related AEs were low across groups. Dose-related increases in the incidence of hypoglycemia episodes were seen with canagliflozin versus placebo in patients on background sulfonylurea; incidences of severe hypoglycemia were low across groups. Hypoglycemia incidence was low overall in patients not on background sulfonylurea, but slightly higher with canagliflozin versus placebo. Relative to placebo, favorable changes in high-density lipoprotein cholesterol and triglycerides were seen with canagliflozin; increases in low-density lipoprotein cholesterol were also seen. Canagliflozin was associated with small changes in other safety laboratory parameters that were not clinically meaningful. Conclusions: Canagliflozin as monotherapy and as combination therapy was generally well tolerated in patients with T2DM inadequately controlled on their current diabetes mellitus treatment. PMID:24918789

Usiskin, Keith; Kline, Irina; Fung, Albert; Mayer, Cristiana; Meininger, Gary; Usiskin, Keith; Kline, Irina; Fung, Albert; Mayer, Cristiana; Meininger, Gary

2014-05-01

269

The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data  

PubMed Central

Background Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. Methods and Findings A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n?=?7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan–Meier survival estimates were 97.7% (95% CI 97.3%–98.1%) at day 42 and 97.2% (95% CI 96.7%–97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3–2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%–96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%–21%) for every 5 mg/kg decrease in dose; p?=?0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. Conclusions DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation. Please see later in the article for the Editors' Summary

2013-01-01

270

[18F]Fluorodeoxyglucose-positron emission tomography screening for lung cancer: a systematic review and meta-analysis  

PubMed Central

Abstract Rationale and objectives: Although low-dose computed tomography (CT) is a recommended modality for lung cancer screening in high-risk populations, the role of other modalities, such as [18F]fluorodeoxyglucose-positron emission tomography (PET), is unclear. We conducted a systematic review to describe the role of PET in lung cancer screening. Materials and methods: A systematic review was conducted by reviewing primary studies focusing on PET screening for lung cancer until July 2012. Two independent reviewers identified studies that were compatible for inclusion/exclusion criteria. The analysis was restricted to English and included studies published since 2000. A descriptive analysis was used to summarize the results, and the pooled diagnostic performance of selective PET screening was calculated by weighted average using individual sample sizes. Results: Among the identified studies (n?=?3497), 12 studies were included for analysis. None of the studies evaluated the efficacy of primary PET screening specific to lung cancer. Eight studies focused on primary PET screening for all types of cancer; the detection rates of lung cancer were low. Four studies reported evidence of lung cancer screening programs with selective PET, in which the estimated pooled sensitivity and specificity was 83% and 91%, respectively. Conclusions: The role of primary PET screening for lung cancer remains unknown. However, PET has high sensitivity and specificity as a selective screening modality. Further studies must be conducted to evaluate the use of PET or PET/computed tomography screening for high-risk populations, preferably using randomized trials or prospective registration. Advances in knowledge: Our meta-analysis indicates that PET has high sensitivity and specificity as a selective screening modality.

Chien, Chun-Ru; Liang, Ji-An; Chen, Jin-Hua; Wang, Hsiao-Nin; Lin, Cheng-Chieh; Chen, Chih-Yi; Wang, Pin-Hui; Yeh, Jun-Jun

2013-01-01

271

Association of XPC Polymorphisms and Lung Cancer Risk: A Meta-Analysis  

PubMed Central

Background Xeroderma pigmentosum complementation group C gene (XPC) is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive. Method This meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT) and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias were detected by Egger’s and Begg’s test. Result After strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR?=?1.229, 95% CI: 1.000–1.510; GlnGln vs LysLys/LysGln, OR?=?1.257, 95% CI: 1.038–1.522). As for the PAT polymorphism, in Caucasian population, we found carriers of the ?/? genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (?/? vs +/+, OR?=?0.735, 95% CI: 0.567–0.952). Conclusion In this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT ?/? genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

Jin, Bo; Dong, Yu; Zhang, Xueyan; Wang, Huimin; Han, Baohui

2014-01-01

272

Swimming pool granuloma  

MedlinePLUS

A swimming pool granuloma is a long-term (chronic) skin infection. It is caused by the bacteria Mycobacterium marinum . ... A swimming pool granuloma occurs when water containing Mycobacterium marinum bacteria enters a break in the skin. Signs of ...

273

Sentinel lymph node biopsy in cervical cancer: A meta-analysis  

PubMed Central

Sentinel lymph node biopsy (SLNB) is used to determine the pathological status of the first lymph node receiving lymphatic drainage from the primary tumor. The diagnostic value of SLNB for the assessment of the nodal status in patients with cervical cancer has not been determined. Therefore, this meta-analysis was conducted to assess the diagnostic value of SLNB in cervical cancer. A search for related literature was performed using PubMed. Data were analyzed using a random effects model and a subgroup analysis was used to assess the diagnostic value of different practices during the process. A total of 17 studies involving a total of 1,112 patients were included in the analysis. The pooled sentinel lymph node (SLN) detection rate, sensitivity and negative predictive values were 92.2% [95% confidence interval (CI): 88.3–94.8%], 88.8% (95% CI: 85.1–91.7%) and 95.0% (95% CI: 92.8–96.6%), respectively. The subgroup analysis revealed that laparoscopy, tracer combination and immunohistochemistry were associated with a higher SLN detection rate. In conclusion, the SLNB in cervical cancer appears to be of diagnostic value, particularly the procedure with the combination of laparoscopy, combined tracers and immunohistochemistry. However, further studies are required to establish the clinical value of SLNB in cervical cancer.

WU, YIBO; LI, ZEMING; WU, HAIYAN; YU, JINJIN

2013-01-01

274

Virtual Tide Pool  

NSDL National Science Digital Library

Virtual Tide Pool features a three dimensional view of a tide pool during both low and high tides. Students can see animals that live under, above, and at the waters surface. This site offers the ability to pan the tide pool for a 360 degree view, with zoom options, and gives descriptions of the animals found during both low and high tides.

Science NetLinks (PBS;)

2003-04-29

275

Analysis of trihalomethanes in water and air from indoor swimming pools using HS-SPME\\/GC\\/ECD  

Microsoft Academic Search

Headspace solid phase microextraction (HS-SPME) with further quantification by gas chromatography and electron capture detector (GC\\/ECD) was used to analyze trihalomethanes (THMs) in water and air from indoor swimming pools (ISPs). High correlation coefficients were obtained for the calibration lines in water with detection limits of 0.2 ?g\\/L for trichloromethane (TCM) and bromodichloromethane (BDCM), 0.1 ?g\\/L for dibromochloromethane (DBCM) and

Christopher S. A. Sá; Rui A. R. Boaventura; Isabel B. Pereira

2011-01-01

276

Association analysis of mild mental impairment using DNA pooling to screen 432 brain-expressed single-nucleotide polymorphisms.  

PubMed

We hypothesize that mild mental impairment (MMI) represents the low extreme of the same quantitative trait loci (QTLs) that operate throughout the distribution of intelligence. To detect QTLs of small effect size, we employed a direct association strategy by genotyping 432 presumably functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) identified from public databases on DNA pools of 288 cases and 1025 controls. In total, 288 MMI cases were identified by in-home administration of McCarthy Scales of Children's Abilities to 836 twin pairs selected from a community sample of more than 14 000 children previously screened for nonverbal cognitive delay using parentally administered tests. Controls were selected from the community sample representing the full range of nonverbal intelligence. SNPs showing at least 7% allele frequency differences between case and control DNA pools were tested for their association with the full range of nonverbal intelligence using five DNA subpools, each representing quintiles of the normal quantitative trait scores from the 1025 controls. SNPs showing linear associations in the expected direction across quintiles using pooled DNA were individually genotyped for the 288 cases and 1025 controls and analyzed using standard statistical methods. One SNP (rs1136141) in HSPA8 met these criteria, yielding a significant (P=0.036) allelic frequency difference between cases and controls for individual genotyping and a significant (P=0.013) correlation within the control group that accounts for 0.5% of the variance. The present SNP strategy combined with DNA pooling and large samples represents a step towards identifying QTLs of small effect size associated with complex traits in the postgenomic era when all functional polymorphisms will be known. PMID:15452586

Butcher, L M; Meaburn, E; Dale, P S; Sham, P; Schalkwyk, L C; Craig, I W; Plomin, R

2005-04-01

277

GSTP1 Ile105Val polymorphism is associated with lung cancer risk among Asian population and smokers: An updated meta-analysis.  

PubMed

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95 % CI 0.99-1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95 % CI 0.96-1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger's test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers. PMID:24566690

Xu, Chun-Hua; Wang, Qin; Zhan, Ping; Qian, Qian; Yu, Li-Ke

2014-07-01

278

Numerical analysis of intensity signals resulting from genotyping pooled DNA samples in beef cattle and broiler chicken.  

PubMed

Pooled genomic DNA has been proposed as a cost-effective approach in genomewide association studies (GWAS). However, algorithms for genotype calling of biallelic SNP are not adequate with pooled DNA samples because they assume the presence of 2 fluorescent signals, 1 for each allele, and operate under the expectation that at most 2 copies of the variant allele can be found for any given SNP and DNA sample. We adapt analytical methodology from 2-channel gene expression microarray technology to SNP genotyping of pooled DNA samples. Using 5 datasets from beef cattle and broiler chicken of varying degrees of complexity in terms of design and phenotype, continuous and dichotomous, we show that both differential hybridization (M = green minus red intensity signal) and abundance (A = average of red and green intensities) provide useful information in the prediction of SNP allele frequencies. This is predominantly true when making inference about extreme SNP that are either nearly fixed or highly polymorphic. We propose the use of model-based clustering via mixtures of bivariate normal distributions as an optimal framework to capture the relationship between hybridization intensity and allele frequency from pooled DNA samples. The range of M and A values observed here are in agreement with those reported within the context of gene expression microarray and also with those from SNP array data within the context of analytical methodology for the identification of copy number variants. In particular, we confirm that highly polymorphic SNP yield a strong signal from both channels (red and green) while lowly or nonpolymorphic SNP yield a strong signal from 1 channel only. We further confirm that when the SNP allele frequencies are known, either because the individuals in the pools or from a closely related population are themselves genotyped, a multiple regression model with linear and quadratic components can be developed with high prediction accuracy. We conclude that when these approaches are applied to the estimation of allele frequencies, the resulting estimates allow for the development of cost-effective and reliable GWAS. PMID:24663186

Reverter, A; Henshall, J M; McCulloch, R; Sasazaki, S; Hawken, R; Lehnert, S A

2014-05-01

279

Prevalence of high-risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population--a pooled analysis from three studies.  

PubMed

Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening. PMID:22907663

Basu, Partha; Mittal, Srabani; Bhaumik, Suchismita; Mandal, Shyam Sunder; Samaddar, Anusree; Ray, Chinmayi; Siddiqi, Maqsood; Biswas, Jaydip; Sankaranarayanan, Rengaswamy

2013-04-01

280

Leisure-time physical activity and lung cancer: a meta-analysis  

PubMed Central

Objective Several studies have evaluated the relationship between physical activity and lung cancer. To summarize and review these studies, we conducted a meta-analysis of all relevant reports published from 1966 through October 2003. Method Adjusted odds ratios (ORs) from the original studies were pooled by the inverse of their variance, and all pooled estimates were accompanied by an assessment of heterogeneity across investigations. Test for linear trend across activity categories (low, moderate, high) were applied. Results The combinedORs were 0.87 (95%confidence interval = 0.79–0.95) for moderate leisure-time physical activity (LPA) and 0.70 (0.62–0.79) for high activity (p trend = 0.00). This inverse association occurred for both sexes, although it was somewhat stronger for women. No evidence of publication bias was found. Several studies were able to adjust for smoking, but none adjusted for possible confounding from previous malignant respiratory disease. Our simulations suggest that this condition is unlikely to entirely explain the inverse association. Conclusion The findings of this meta-analysis indicate that higher levels of LPAprotect against lung cancer. The inverse association is possible remains confounded by inadequately controlled smoking patterns. However on the whole, confounding seems an unlikely explanation for the findings of individual studies on non-smokers.

Tardon, Adonina; Lee, Won Jin; Delgado-Rodriguez, Miguel; Dosemeci, Mustafa; Albanes, Demetrius; Hoover, Robert; Blair, Aaron

2005-01-01

281

Systematic review and meta-analysis of insulin therapy and risk of cancer.  

PubMed

Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. A search of online database through January 2011 was performed and examined the reference lists of pertinent articles, limited to observational studies in humans. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Fifteen studies (five case-control and ten cohort studies) were included, with 562,043 participants and 14,085 cases of cancer. Insulin treatment was associated with an increased risk of overall cancer [summary RR (95% CI)=1.39 (1.14, 1.70)]. Summary RR (9% CI) for case-control studies was 1.83 (0.99, 3.38), whereas RR for cohort studies was 1.28 (1.03, 1.59). These results were consistent between studies conducted in the USA and in Europe. For studies that included combined type 1 and 2 diabetes, the summary estimate was stronger than studies including only type 2 diabetes mellitus. The association between insulin treatment and cancer was stronger for pancreatic cancer [summary RR (95% CI)=4.78 (3.12, 7.32)] than for colorectal cancer [1.50 (1.08, 2.08)]. Insulin treatment was not associated with breast, prostate, and hepatocelluar cancer, and their effect estimates were not statistically significant. Our findings support an association between insulin use and increased risk of overall, pancreatic, and colorectal cancer. PMID:22528451

Janghorbani, Mohsen; Dehghani, Mohsen; Salehi-Marzijarani, Mohammad

2012-08-01

282

Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases.  

National Technical Information Service (NTIS)

This annual report for the Physician Research Training Award focuses on progress in the genetic analysis of circulating hormone refractory prostate cancer micrometastases. As metastatic tissue is often inaccessible in advanced prostate cancer patients, an...

J. Rosenberg

2009-01-01

283

Bayesian Pathway Analysis of Cancer Microarray Data  

PubMed Central

High Throughput Biological Data (HTBD) requires detailed analysis methods and from a life science perspective, these analysis results make most sense when interpreted within the context of biological pathways. Bayesian Networks (BNs) capture both linear and nonlinear interactions and handle stochastic events in a probabilistic framework accounting for noise making them viable candidates for HTBD analysis. We have recently proposed an approach, called Bayesian Pathway Analysis (BPA), for analyzing HTBD using BNs in which known biological pathways are modeled as BNs and pathways that best explain the given HTBD are found. BPA uses the fold change information to obtain an input matrix to score each pathway modeled as a BN. Scoring is achieved using the Bayesian-Dirichlet Equivalent method and significance is assessed by randomization via bootstrapping of the columns of the input matrix. In this study, we improve on the BPA system by optimizing the steps involved in “Data Preprocessing and Discretization”, “Scoring”, “Significance Assessment”, and “Software and Web Application”. We tested the improved system on synthetic data sets and achieved over 98% accuracy in identifying the active pathways. The overall approach was applied on real cancer microarray data sets in order to investigate the pathways that are commonly active in different cancer types. We compared our findings on the real data sets with a relevant approach called the Signaling Pathway Impact Analysis (SPIA).

Korucuoglu, Melike; Isci, Senol; Ozgur, Arzucan; Otu, Hasan H.

2014-01-01

284

Consumption of omega-3 fatty acids and the risk of skin cancers: a systematic review and meta-analysis.  

PubMed

Skin cancers have a higher incidence than all other cancers combined and are a major cause of morbidity worldwide. Laboratory data suggest certain dietary constituents, notably omega-3 polyunsaturated fatty acids (n-3 PUFAs), could potentially protect against skin malignancy, although no large-scale review has been conducted in humans. The objective of this review and meta-analysis was to determine the relationship between dietary n-3 PUFAs and skin cancer incidence. It considered all published randomized controlled trials and observational studies up to March 2013. Five studies (two case-control and three cohort) were identified pertaining to oral n-3 PUFA consumption and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (or a combination) and were included in a random-effects meta-analysis. A further six studies considering nondietary n-3 PUFA exposure (e.g., by tissue analysis) and/or recognized biological markers of skin cancer risk (e.g., p53 expression) were analyzed qualitatively. Dietary n-3 PUFAs were not associated with BCC (pooled OR 1.05, 95% CIs 0.86-1.28). Consumption of high levels of n-3 PUFAs were inversely associated with melanoma, although with only one estimate available (OR 0.52, 95% CI 0.34-0.78), and SCC, although nonsignificantly (pooled OR 0.86, 95% CIs 0.59-1.23). Available evidence is suggestive, but currently inadequate, to support the hypothesis that n-3 PUFAs protect against skin malignancy. PMID:24265065

Noel, Sophie E; Stoneham, Adam C S; Olsen, Catherine M; Rhodes, Lesley E; Green, Adele C

2014-07-01

285

Diagnostic Value of Circulating microRNAs for Lung Cancer: A Meta-Analysis  

PubMed Central

Background: Lung cancer is a leading cause of cancer mortality, and it shows a high incidence worldwide. Circulating microRNAs have been proposed as diagnostic indicators of lung cancer, but inconsistent results in the literature have prevented their widespread use in diagnosis. The present meta-analysis aimed to systematically evaluate the diagnostic accuracy of circulating microRNAs for lung cancer. Methods: Several research databases were searched systematically for studies of the accuracy of circulating microRNAs as diagnostic indicators of lung cancer. Results from different studies were pooled using random-effects models. Summary receiver operating characteristic (SROC) curves were used to assess the overall performance of microRNA-based assays. Results: Thirteen publications were included in the meta-analysis. The following summary estimates were obtained for the performance of circulating microRNAs in lung cancer diagnosis: sensitivity, 0.85 (95% confidence intervals [CI]: 0.83–0.87); specificity, 0.84 (95% CI: 0.81–0.86); positive likelihood ratio, 5.23 (95% CI: 3.75–7.29); negative likelihood ratio, 0.20 (95% CI: 0.14–0.27); and diagnostic odds ratio, 31.77 (95% CI: 16.98–59.42). The SROC curve indicated a maximum joint sensitivity and specificity of 0.85, with an area under the curve of 0.92. Conclusion: Circulating microRNAs show significant potential as diagnostic markers of lung cancer. The results of this meta-analysis justify larger, more rigorous studies to confirm such a diagnostic role.

Shen, Yongchun; Wang, Tao; Yang, Ting; Hu, Qianjing; Wan, Chun; Chen, Lei

2013-01-01

286

Association between CD14 Gene Polymorphisms and Cancer Risk: A Meta-Analysis  

PubMed Central

Background Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. Methods All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of this association in fixed- or random-effects model. Results 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls) for -260C/T polymorphism and three studies (832 cases and 1190 controls) for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori) infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. Conclusions This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

Wang, Jun; Guo, Xufeng; Yu, Shijie; Song, Jia; Zhang, Jixiang; Cao, Zhuo; Wang, Jing; Liu, Min; Dong, Weiguo

2014-01-01

287

Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials.  

PubMed

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to 30 versus or=70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia. PMID:20013016

Horn, D L; Ostrosky-Zeichner, L; Morris, M I; Ullmann, A J; Wu, C; Buell, D N; Kovanda, L L; Cornely, O A

2010-02-01

288

Optical spectra analysis for breast cancer diagnostics  

NASA Astrophysics Data System (ADS)

Minimally invasive probe and optical biopsy system based on optical spectra recording and analysis seem to be a promising tool for early diagnostics of breast cancer. Light scattering and absorption spectra are generated continuously as far as the needle-like probe with one emitting and several collecting optical fibers penetrates through the tissues toward to the suspicious area. That allows analyzing not only the state of local site, but also the structure of tissues along the needle trace. The suggested method has the advantages of automated on-line diagnosing and minimal tissue destruction and in parallel with the conventional diagnostic procedures provides the ground for decision-making. 165 medical trials were completed in Nizhny Novgorod Regional Oncology Centre, Russia. Independent diagnoses were the results of fine biopsy and histology. Application of wavelet expansion and clasterization techniques for spectra analysis revealed several main spectral types for malignant and benign tumors. Automatic classification algorithm demonstrated specificity ˜90% and sensitivity ˜91%. Large amount of information, fuzziness in criteria and data noisiness make neural networks to be an attractive analytic tool. The model based on three-layer perceptron was tested over the sample of 29 `cancer' and 29 `non-cancer' cases and demonstrated total separation.

Belkov, S. A.; Kochemasov, G. G.; Lyubynskaya, T. E.; Maslov, N. V.; Nuzhny, A. S.; da Silva, L. B.; Rubenchik, A.

2011-11-01

289

Geographic and Temporal Trends in the Management of Occult Primary Breast Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Background Management of occult primary breast cancer (OPBC), including the role of magnetic resonance imaging (MRI), is controversial. We conducted a pooled analysis of OPBC patients and a meta-analysis of MRI accuracy in OPBC in order to elucidate current practices. Methods A literature search yielded 201 studies. Patient-level data for clinically/mammographically OPBC from studies published after 1993 and from our institution were pooled; logistic regression examined associations between patient/study data and outcomes, including treatments and recurrence. We report adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI) significant at 2-tailed p<0.05. Meta-analysis included data for patients who received MRIs for workup of clinically/mammographically OPBC. We report pooled sensitivity and specificity with 95 % CIs. Results The pooled analysis included 92 patients (15 studies [n = 85] plus our institution [n = 7]). Patients from Asia were more likely to receive breast surgery (OR = 5.98, 95 % CI = 2.02–17.65) but not chemotherapy (OR = 0.32, 95 % CI = 0.13–0.82); patients from the United States were more likely to receive chemotherapy (OR = 13.08, 95 % CI = 2.64–64.78). Patients from studies published after 2003 were more likely to receive radiotherapy (OR = 3.86, 95 % CI = 1.41–10.55). Chemotherapy recipients were more likely to have distant recurrence (OR = 9.77, 95 % CI = 1.10–87.21). More patients with positive MRIs received chemotherapy than patients with negative MRIs (10 of 12 [83.3 %] vs 5 of 13 [38.5 %]; p = 0.0414). In the MRI-accuracy meta-analysis (10 studies, n = 262), pooled sensitivity and specificity were 96 % (95 % CI = 91–98 %) and 63 % (95 % CI = 42–81 %), respectively. Conclusions OPBC management varied geographically and over time. We recommend establishing an international OPBC patient registry to facilitate longitudinal study and develop global treatment standards.

Fayanju, Oluwadamilola M.; Stoll, Carolyn R. T.; Fowler, Susan; Colditz, Graham A.; Jeffe, Donna B.; Margenthaler, Julie A.

2013-01-01

290

Occupational exposures to polycyclic aromatic hydrocarbons and respiratory and urinary tract cancers: an updated systematic review and a meta-analysis to 2014.  

PubMed

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with an excess risk of respiratory tract and bladder cancers in several industries, but the issue requires further quantification. We updated a previous systematic review by reviewing in details cohort studies on workers employed in selected industries with potential PAH exposure published between 2006 and 2014, and we summarized through a meta-analytic approach the main results of all available cohort studies published between 1958 and 2014 investigating cancers of the respiratory and urinary tracts. Thirteen papers on cohort studies investigating cancer risk in workers exposed to PAHs were retrieved through the literature search. These included workers from aluminum production industries (seven studies), iron and steel foundries (two studies), asphalt workers (two studies), and carbon black production (two studies). In the meta-analysis, an excess risk of respiratory tract cancers (mainly lung cancer) was found in iron and steel foundries [pooled relative risk (RR) 1.31, 95 % confidence interval (CI) 1.08-1.59 from 14 studies], while a weak excess risk (pooled RR 1.08, 95 % CI 0.95-1.23 from 11 studies) emerged for aluminum production. A borderline increase risk was also observed for cancer of the bladder in the aluminum production (pooled RR 1.28, 95 % CI 0.98-1.68 from 10 studies) and in iron and steel foundries (pooled RR 1.38, 95 % CI 1.00-1.91 from 9 studies). This updated review and meta-analysis confirm the increased risk from respiratory tract and bladder cancers in selected PAH-related occupations. It cannot be ruled out whether such excesses are due, at least in part, to possible bias or residual confounding. PMID:24935254

Rota, Matteo; Bosetti, Cristina; Boccia, Stefania; Boffetta, Paolo; La Vecchia, Carlo

2014-08-01

291

Oxaliplatin-based Chemotherapy: A New Option in Advanced Hepatocellular Carcinoma. A Systematic Review and Pooled Analysis.  

PubMed

Advanced hepatocellular carcinoma (HCC), for which locoregional treatment is not an option, is a candidate for palliative systemic therapy, but an accepted chemotherapy regimen does not exist. We have conducted a systematic literature review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based chemotherapy in advanced HCC in patients not exposed to sorafenib. Studies that enrolled advanced HCC patients treated with first-line OXA-based chemotherapy were identified using PubMed, Web of Science, SCOPUS, The Cochrane Register of Controlled Trials and EMBASE. A systematic review was conducted to calculate the pooled response rate and 95% confidence interval. The pooled median progression-free survival (PFS) and overall survival, weighted on the number of patients of each selected trials, were also calculated. We tested for significant heterogeneity by Cochran's chi-squared test and I-square index. Thirteen studies were included in this review, with a total of 800 patients analysed. The pooled response rate was 16.8%. The median PFS and overall survival were 4.2 and 9.3 months, respectively, with a 1 year overall survival of 37%. The weighted median PFS/overall survival and response rate were 4.5/11 months and 20% in Western patients. Conversely, in Asiatic studies, the median PFS/overall survival and response rate were 2.43/6.47 months and 13.2%, respectively. OXA-based chemotherapy is effective in advanced HCC and represents a viable option in these patients. A head to head comparison with sorafenib or a second-line agent should be verified in prospective trials. PMID:24856442

Petrelli, F; Coinu, A; Borgonovo, K; Cabiddu, M; Ghilardi, M; Lonati, V; Barni, S

2014-08-01

292

The Association of Retinoic Acid Receptor Beta2(RAR?2) Methylation Status and Prostate Cancer Risk: A Systematic Review and Meta-Analysis  

PubMed Central

The retinoic acid receptor beta2(RAR?2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RAR?2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RAR?2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RAR?2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RAR?2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI?=?6.30–49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI?=?0.40–1.09) and the pooled OR of low-GS in RAR?2 methylated patients by the random-effect model, compared to high-GS RAR?2 methylated patients, was 0.54 (95%CI?=?0.28–1.04). This study showed that RAR?2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RAR?2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies.

Pan, Yuqin; Li, Rui; Xu, Yeqiong; Chen, Liping; Nie, Zhenling; Gu, Ling; Wang, Shukui

2013-01-01

293

CA19-9 and CA242 as tumor markers for the diagnosis of pancreatic cancer: a meta-analysis.  

PubMed

Pancreatic cancer has the worst prognosis of any gastrointestinal cancer, with the mortality approaching the incidence. Early detection is crucial for improving patient prognosis. We therefore performed a meta-analysis to evaluate and compare the sensitivity and specificity of CA19-9 and CA242 in pancreatic cancer. We searched PubMed, EMBASE, and the Cochrane Library for studies that evaluated the diagnostic validity of CA19-9 and CA242 between January 1966 and March 2011. Meta-analysis methods were used to pool sensitivity and specificity and to construct a summary receiver-operating characteristic (SROC) curve. A total of 11 studies that included 2,316 patients who fulfilled all of the inclusion criteria were considered for analysis. The pooled sensitivities for CA242 and CA19-9 were 0.719 (95 % confidence interval [CI] 0.690-0.746) and 0.803 (95 % CI 0.777-0.826), respectively. The pooled specificities of CA242 and CA19-9 were 0.868 (95 % CI 0.849-0.885) and 0.802 (95 % CI 0.780-0.823), respectively. The diagnostic odds ratio (DOR) estimate was significantly higher for CA242 (16.261) than for CA19-9 (15.637). Our meta-analysis showed that CA242 and CA19-9 could play different roles in the diagnosis of pancreatic cancer. Although the sensitivity of CA242 is lower than that of CA19-9, its specificity is greater. PMID:23456571

Gui, Ji-Cong; Yan, Wei-Li; Liu, Xing-Dang

2014-05-01

294

Trace elements determinations in cancerous and non-cancerous human tissues using instrumental neutron activation analysis  

SciTech Connect

Recent improvements in analyzing techniques when coupled to the growing knowledge of trace element biochemistry provide a powerful tool to investigate the relationship between trace elements and cancer. It is hoped that selective delivery or restriction of specific minerals may aid in cancer prevention or treatment. Tissues were collected at the time of surgery of various cancer patients including colon cancer and breast cancer. Three kinds of tissues were taken from a patient; cancerous, noncancerous, and transitional tissue obtained from a region located between the cancer and healthy tissues. A total of 57 tissues were obtained from 19 cancer patients. Seven of them were colon cancer patients, and 5 of them were breast cancer patients. Nine elements were determined using instrumental activation analysis. Cancerous colon tissue had significantly higher concentrations of selenium and iron than healthy tissues. Cancerous breast tissue had significantly higher concentrations of selenium, iron, manganese, and rubidium than healthy tissues. Iron can be enriched in cancer tissue because cancer tissue retains more blood vessels. Selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumors. The manganese enrichment can be explained in the same manner as selenium considering its suspected anticarcinogenicity. It is not certain why rubidium was enriched in cancer tissue. It could be that this is the result of alteration of cell membrane permeability, change in extracellular matrix, or increased metabolism in cancer tissue.

Choi, Insup.

1989-01-01

295

A systems biology analysis of autophagy in cancer therapy.  

PubMed

Autophagy, which degrades redundant or damaged cellular constituents, is intricately relevant to a variety of human diseases, most notably cancer. Autophagy exerts distinct effects on cancer initiation and progression, due to the intrinsic overlapping of autophagic and cancer signalling pathways. However, due to the complexity of cancer as a systemic disease, the fate of cancer cells is not decided by any one signalling pathway. Numerous autophagic inter-connectivity and cross-talk pathways need to be further clarified at a systems level. In this review, we propose a systems biology perspective for the comprehensive analysis of the autophagy-cancer network, focusing on systems biology analysis in autophagy and cancer therapy. Together, these analyses may not only improve our understanding on autophagy-cancer relationships, but also facilitate cancer drug discovery. PMID:23791881

Shi, Zheng; Li, Chun-yang; Zhao, Si; Yu, Yang; An, Na; Liu, Yong-xi; Wu, Chuan-fang; Yue, Bi-song; Bao, Jin-ku

2013-09-01

296

Occupational Exposure to Asbestos and Ovarian Cancer: A Meta-analysis  

PubMed Central

Objective: A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association. Data sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos. Data extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. Data synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37–2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger’s test p-value = 0.162). Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer.

Camargo, M. Constanza; Straif, Kurt; Reina, Margarita; Al-Alem, Umaima; Demers, Paul A.; Landrigan, Philip J.

2011-01-01

297

Case-control and prospective studies of dietary ?-linolenic acid intake and prostate cancer risk: a meta-analysis  

PubMed Central

Objective ?-Linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case–control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk. Design A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case–control studies. Included studies We included all prospective cohort, case–control, nested case-cohort and nested case–control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates. Primary outcome measure Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95% CIs. Heterogeneity was assessed by ?2 and quantified by I2. Results Data from five prospective and seven case–control studies were pooled. The overall RR estimate showed ALA intake to be positively but non-significantly associated with prostate cancer risk (1.08 (0.90 to 1.29), p=0.40; I2=85%), but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant (0.91 (0.83 to 0.99), p=0.02) without evidence of heterogeneity (I2=8%, p=0.35) on removal of one study during sensitivity analyses. Conclusions This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer.

Carleton, Amanda J; Sievenpiper, John L; de Souza, Russell; McKeown-Eyssen, Gail; Jenkins, David J A

2013-01-01

298

Method for data analysis in different institutions: example of image guidance of prostate cancer patients.  

PubMed

Multi-institutional collaborations allow for more information to be analyzed but the data from different sources may vary in the subgroup sizes and/or conditions of measuring. Rigorous statistical analysis is required for pooling the data in a larger set. Careful comparison of all the components of the data acquisition is indispensable: identical conditions allow for enlargement of the database with improved statistical analysis, clearly defined differences provide opportunity for establishing a better practice. The optimal sequence of required normality, asymptotic normality, and independence tests is proposed. An example of analysis of six subgroups of position corrections in three directions obtained during image guidance procedures for 216 prostate cancer patients from two institutions is presented. PMID:23721940

Piotrowski, T; Rodrigues, G; Bajon, T; Yartsev, S

2014-03-01

299

Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies  

PubMed Central

Objectives Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. Methods Six research groups collected prospective data at >50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. Results At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. Conclusions Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure– response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference.

Dale, Ann Marie; Harris-Adamson, Carisa; Rempel, David; Gerr, Fred; Hegmann, Kurt; Silverstein, Barbara; Burt, Susan; Garg, Arun; Kapellusch, Jay; Merlino, Linda; Thiese, Matthew S; Eisen, Ellen A; Evanoff, Bradley

2014-01-01

300

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme  

PubMed Central

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5?mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1?year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%). Conclusions Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need.

Holz, Frank G; Bandello, Francesco; Gillies, Mark; Mitchell, Paul; Osborne, Aaron; Sheidow, Tom; Souied, Eric; Figueroa, Marta S

2013-01-01

301

Perioperative blood transfusion adversely affects prognosis after resection of lung cancer: a systematic review and a meta-analysis  

PubMed Central

Background It is speculated that blood transfusion may induce adverse consequences after cancer surgery due to immunosuppression. This study was intended to assess the impact of perioperative blood transfusion on the prognosis of patients who underwent lung cancer resection. Methods Eligible studies were identified through a computerized literature search. The pooled relative risk ratio (RR) with 95% confidence interval (CI) was calculated using Review Manager 5.1 Software. Results Eighteen studies with a total of 5915 participants were included for this meta-analysis. Pooled analysis showed that perioperative blood transfusion was associated with worse overall survival (RR: 1.25, 95% CI: 1.13-1.38; P <0.001) and recurrence-free survival (RR: 1.42, 95% CI: 1.20-1.67; P <0.001) in patients with resected lung cancer. Conclusions Perioperative blood transfusion appears be associated with a worse prognosis in patients undergoing lung cancer resection. These data highlight the importance of minimizing blood transfusion during surgery.

2014-01-01

302

An Aggregated Analysis of Hormonal Factors and Endometrial Cancer Risk by Parity  

PubMed Central

Background Nulliparity is associated with an increased risk of endometrial cancer. Less clear is whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies are too small to test the hypothesis that endometrial cancer risk factors may be more strongly associated with risk among nulliparous women compared with parous women. Methods We aggregated data on 26,936 postmenopausal, Caucasian nulliparous women (360 endometrial cancers) and 146,583 postmenopausal Caucasian parous women (1,378 endometrial cancers) from four U.S. prospective studies (1979–2006). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) in stratified analyses. Results As expected, endometrial cancer risk was higher among nulliparous women than among parous women (HR, nulliparous vs. parous = 1.42, 95% CI 1.26 to 1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ among nulliparous vs. parous women: among both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity; body mass index ?30 kg/m2 (vs. <25 kg/m2) increased endometrial cancer risk three-fold among nulliparous (HR= 3.04, 95% CI 2.34 to 3.94) and parous (HR= 2.88, 95% CI 2.52 to 3.29) women. Conclusions The results from this large, pooled analysis of data from four large prospective studies suggest that nulliparity does not modify endometrial cancer risks associated with established hormone-related risk factors.

Schonfeld, Sara J.; Hartge, Patricia; Pfeiffer, Ruth M.; Freedman, D. Michal; Greenlee, Robert T.; Linet, Martha S.; Park, Yikyung; Schairer, Catherine; Visvanathan, Kala; Lacey, JV

2013-01-01

303

Coffee consumption and risk of cancers: a meta-analysis of cohort studies  

PubMed Central

Background Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence. Methods We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to frequency of coffee intake. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with 1 cup/day increment of coffee consumption. Results 59 studies, consisting of 40 independent cohorts, met the inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR of cancer was 0.87 (95% CI, 0.82-0.92) for regular coffee drinkers, 0.89 (0.84-0.93) for low to moderate coffee drinkers, and 0.82 (0.74-0.89) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers (RR, 0.97; 95% CI, 0.96-0.98). In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers. Conclusions Findings from this meta-analysis suggest that coffee consumption may reduce the total cancer incidence and it also has an inverse association with some type of cancers.

2011-01-01

304

Sex Hormones, Hormonal Interventions and Gastric Cancer Risk: A Meta-Analysis  

PubMed Central

Estrogens may influence gastric cancer risk but published studies are inconclusive. We therefore performed a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors, and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR= 0.74; 95% CI= 0.63 to 0.86) and HRT (RR= 0.77, 95% CI= 0.64 to 0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR= 1.82, 95% CI= 1.39 to 2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms.

Camargo, M. Constanza; Goto, Yasuyuki; Zabaleta, Jovanny; Morgan, Douglas R.; Correa, Pelayo; Rabkin, Charles S.

2011-01-01

305

Internet cancer support groups: a feminist analysis.  

PubMed

Internet Cancer Support Groups (ICSGs) are an emerging form of support group on Internet specifically for cancer patients. Previous studies have indicated the effectiveness of ICSGs as a research setting or a data-collection method. Yet recent studies have also indicated that ICSGs tend to serve highly educated, high-income White males who tend to be at an early stage of cancer. In this article, a total of 317 general ICSGs and 229 ethnic-specific ICSGs searched through Google.com, Yahoo.com, Msn.com, AOL.com, and ACOR.org are analyzed from a feminist perspective. The written records of group discussions and written memos by the research staff members were also analyzed using content analysis. The idea categories that emerged about these groups include (a) authenticity issues; (b) ethnicity and gender issues; (c) intersubjectivity issues; and (d) potential ethical issues. The findings suggest that (a) researchers adopt multiple recruitment strategies through various Internet sites and/or real settings; (b) researchers raise their own awareness of the potential influences of the health-related resources provided by ICSGs and regularly update their knowledge related to the federal and state standards and/or policies related to ICSGs; and (c) researchers consider adopting a quota-sampling method. PMID:15681976

Im, Eun-Ok; Chee, Wonshik; Tsai, Hsiu-Min; Lin, Li-Chen; Cheng, Ching-Yu

2005-01-01

306

Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis  

PubMed Central

Objective There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer. Design We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of “current use” of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses. Results Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18). Conclusions Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials.

Shah, Nirav R.; Borenstein, Jeff; Dubois, Robert W.

2006-01-01

307

Mutational Analysis of the Tyrosine Phosphatome in Colorectal Cancers  

Microsoft Academic Search

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations

Zhenghe Wang; Dong Shen; D. Williams Parsons; Alberto Bardelli; Jason Sager; Steve Szabo; Janine Ptak; Natalie Silliman; Brock A. Peters; Michiel S. van der Heijden; Giovanni Parmigiani; Hai Yan; Tian-Li Wang; Greg Riggins; Steven M. Powell; James K. V. Willson; Sanford Markowitz; Kenneth W. Kinzler; Bert Vogelstein; Victor E. Velculescu

2004-01-01

308

Cancer Nursing Education: Literature Review and Documentary Analysis.  

ERIC Educational Resources Information Center

The knowledge and skills needed by cancer nurses and the content and strategies of England's existing cancer nursing education programs were examined. The study included a comprehensive literature review and an analysis of course documents from selected English National Board-approved post-qualifying cancer nursing and palliative care courses…

Langton, Helen; Blunden, Gillian; Hek, Gill

309

Ectomycorrhizal community structure in a xeric Quercus woodland based on rDNA sequence analysis of sporocarps and pooled roots.  

PubMed

Quercus woodlands are key components of California's wild landscapes, yet little is known about ectomycorrhizal (EM) fungi in these ecosystems. We examined the EM community associated with Quercus douglasii using sporocarp surveys and by pooling EM roots and subjecting them to DNA extraction, polymerase chain reaction (PCR), cloning, restriction fragment length polymorphism (RFLP) screening and DNA sequencing. Ectomycorrhizal root symbionts were sampled four times in 2003-04. During this time, the below-ground community structure was relatively stable; we found no evidence of taxa adapted to winter or spring conditions and only one species varied widely in occurrence between years. The EM community from sporocarps and roots was diverse (161 species), rich in Ascomycota (46 species), and dominated by fungi with cryptic sporocarps. This included a large number of resupinate and hypogeous taxa, many of which were detected both above- and below-ground. PMID:17504467

Smith, Matthew E; Douhan, Greg W; Rizzo, David M

2007-01-01

310

A simulation-based analysis of motor unit number index (MUNIX) technique using motoneuron pool and surface electromyogram models.  

PubMed

Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M-wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M-wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

2012-05-01

311

A Simulation Based Analysis of Motor Unit Number Index (MUNIX) Technique Using Motoneuron Pool and Surface Electromyogram Models  

PubMed Central

Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size.

Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

2013-01-01

312

Enhanced Recovery after Elective Open Surgical Repair of Abdominal Aortic Aneurysm: A Complementary Overview through a Pooled Analysis of Proportions from Case Series Studies  

PubMed Central

Objectives To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) programs in elective open surgical repair (OSR) of abdominal aortic aneurysm (AAA). Background Open surgical repair of AAA is associated with high morbidity and mortality, prolonged hospital stay and high costs. ERAS programs contribute to the optimization of treatment by reducing hospital stay and improving clinical outcomes. Methods A review of PubMed, EMBASE and LILACS databases was conducted. As only one randomized controlled trial was found, a pooled analysis of proportions from case series was conducted, considering it a complementary overview of the topic. Inclusion criteria were case series with more than five cases reported, adult patients who underwent an elective OSR of AAA and use of an ERAS program. ERAS was compared to conventional perioperative care. The pooled proportion and the confidence interval (CI) are shown for each outcome. The overlap of the CI suggests similar effect of the interventions studied. Results Thirteen case series studies with ERAS involving 1,250 patients were compared to six case series with conventional care with a total of 1,429 patients. The pooled, respective proportions for ERAS and conventional care were: mortality, 1.51% [95% CI: 0.0091, 0.0226] and 3.0% [95% CI 0.0183, 0.0445]; and incidence of complications, 3.82% [95% CI 0.0259, 0.0528] and 4.0% [95% CI 0.03, 0.05]. Conclusion This review shows that ERAS and conventional care therapies have similar mortality and complication rates in OSR of AAA.

Gurgel, Sanderland J. T.; El Dib, Regina; do Nascimento, Paulo

2014-01-01

313

Tea consumption and the risk of five major cancers: a dose-response meta-analysis of prospective studies  

PubMed Central

Background We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer. Methods We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ?3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk. Results Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32). Conclusion Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations.

2014-01-01

314

Association between Helicobacter pylori Infection and Pancreatic Cancer Development: A Meta-Analysis  

PubMed Central

Background Pancreatic cancer is one of the most troublesome malignancies with dismal prognosis. H. pylori has been recognized as a type I carcinogen. Several studies have evaluated the association between H. pylori infection and pancreatic cancer development, however, the conclusions are inconsistent. Methods Literature search was carried out in PubMed, EMBASE, Cochrane Library and CNKI databases to identify eligible researches. We performed overall meta-analysis of all studies included and subgroup analysis based on regional distribution. Quality of the studies (assessed by Newcastle-Ottawa quality assessment scale for case-control studies) and CagA+ strains of H. pylori were taken into consideration, and we conducted additional analyses including high-quality researches and those concerning CagA+ H. pylori respectively. Results 9 studies involving 3033 subjects (1083 pancreatic cancer cases, 1950 controls) were included. Summary OR and 95%CI of the overall meta-analysis of all included studies were 1.47 and 1.22-1.77, pooled data of the 4 high-quality studies were OR 1.28, 95%CI 1.01-1.63. OR of the 5 studies examined CagA+ strains was 1.42, corresponding 95%CI was 0.79 to 2.57. Summary estimates of subgroup analysis based on regional distribution are as follows, Europe group: OR 1.56, 95%CI 1.15-2.10; East Asia group: OR 2.01, 95%CI 1.33-3.02; North America group: OR 1.17, 95%CI 0.87-1.58. There was not obvious heterogeneity across the 9 studies. No publication bias was detected. Conclusion H. pylori infection is significantly, albeit weakly, associated with pancreatic cancer development. The association is prominent in Europe and East Asia, but not in North America. CagA+ H. pylori strains appear not to be associated with pancreatic cancer. However, more studies, especially prospective studies, are needed to validate our results.

Gao, Yi

2013-01-01

315

Optimal prediction pools  

Microsoft Academic Search

We consider the properties of weighted linear combinations of prediction models, or linear pools, evaluated using the log predictive scoring rule. Although exactly one model has limiting posterior probability, an optimal linear combination typically includes several models with positive weights. We derive several interesting results: for example, a model with positive weight in a pool may have zero weight if

John Geweke; Gianni Amisano

2011-01-01

316

Proteomic Analysis of Prostate Cancer Field Effect.  

National Technical Information Service (NTIS)

We have undertaken a proteomic approach to identify proteins altered in both cancer and benign cells near the cancers. This study takes advantage of the 'field effect' of the cancer, the malignancy associated changes in normal cells to discover cancer alt...

M. J. Wilson

2008-01-01

317

Proteomic Analysis of Prostate Cancer Field Effect.  

National Technical Information Service (NTIS)

We have undertaken a novel proteomic approach to identify proteins altered in both cancer and benign cells near the cancers. This is to take advantage of the field effect of the cancer, the malignancy associated changes in normal cells, to discover cancer...

M. J. Wilson

2011-01-01

318

Meta-Analysis of Efficacy of Interventions for Elevated Depressive Symptoms in Adults Diagnosed With Cancer  

PubMed Central

Background Cancer patients are at increased risk for depression compared with individuals with no cancer diagnosis, yet few interventions target depressed cancer patients. Methods Efficacy of psychotherapeutic and pharmacologic interventions for depression in cancer patients who met an entry threshold for depressive symptoms was examined by meta-analysis. Five electronic databases were systematically reviewed to identify randomized controlled trials meeting the selection criteria. Effect sizes were calculated using Hedges’ g and were pooled to compare pre- and postrandomization depressive symptoms with a random effects model. Subgroup analyses tested moderators of effect sizes, such as comparison of different intervention modalities, with a mixed effects model. All statistical tests were two-sided. Results Ten randomized controlled trials (six psychotherapeutic and four pharmacologic studies) met the selection criteria; 1362 participants with mixed cancer types and stages had been randomly assigned to treatment groups. One outlier trial was removed from analyses. The random effects model showed interventions to be superior to control conditions on reducing depressive symptoms postintervention (Hedges’ g = 0.43, 95% confidence interval = 0.30 to 0.56, P < .001). In the four psychotherapeutic trials with follow-up assessment, interventions were more effective than control conditions up to 12–18 months after patients were randomly assigned to treatment groups (P < .001). Although each approach was more effective than the control conditions in improving depressive symptoms (P < .001), subgroup analyses showed that cognitive behavioral therapy appeared more effective than problem-solving therapy (P = .01), but not more effective than pharmacologic intervention (P = .07). Conclusions Our findings suggest that psychological and pharmacologic approaches can be targeted productively toward cancer patients with elevated depressive symptoms. Research is needed to maximize effectiveness, accessibility, and integration into clinical care of interventions for depressed cancer patients.

2012-01-01

319

Prognostic Value of CD166 Expression in Cancers of the Digestive System: A Systematic Review and Meta-Analysis  

PubMed Central

Objective Many studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis. Methods A comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected. Results Nine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%–76.3%). In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR?=?0.93, 95%, CI: 0.88–0.98) but worse spread to nearby lymph nodes (N category; RR?=?1.17, 95% CI: 1.05–1.30). The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR?=?1.47 95% 1.21–1.79), but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate. Conclusion Based on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.

Zhu, Xiaotao; Liu, Yang; Qu, Dihong; Wu, Ping; Huang, Jian; Xu, A-xiang

2013-01-01

320

Association between CYP2A6 genetic polymorphisms and lung cancer: a meta-analysis of case-control studies.  

PubMed

Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco-specific carcinogens are metabolized, which in turn determines the incidence of lung cancer. Several studies have investigated the relationship between CYP2A6 genotypes and lung cancer; however, the results are controversial. In this meta-analysis, we searched for all studies on the association between CYP2A6 genotypes and lung cancer indexed in the MEDLINE, PubMed, Embase, China Biological Medicine, and Wanfang databases from January 1, 1966 to August 1, 2011. The pooled odds ratios (ORs) for one CYP2A6 mutant allele and two CYP2A6 mutant alleles, in comparison with the wild-type CYP2A6 gene, were 0.82 [95% confidence interval (CI) = 0.73-0.92] and 0.57 (95% CI = 0.48-0.68), respectively. Furthermore, in two studies of participants who were all smokers, the associations of one CYP2A6 mutant allele and two CYP2A6 mutant alleles with reduced risk of lung cancer were strengthened, and the pooled ORs were 0.71 (95% CI = 0.58-0.87) and 0.47 (95% CI = 0.35-0.62), respectively. However, we did not find statistically significant relationships between CYP2A6 genotypes and lung cancer in studies that included both never smokers and smokers (pooled OR(one CYP2A6 mutant allele) = 0.88, 95% CI = 0.76-1.01; pooled OR(two CYP2A6 mutant alleles) = 0.61, 95% CI = 0.35-1.06). The results of this meta-analysis suggest that the reduced-activity CYP2A6 genotype may decrease the risk of lung cancer in smokers only. PMID:23203414

Liu, Tao; Xie, Chuan-Bo; Ma, Wen-Jun; Chen, Wei-Qing

2013-03-01

321

The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis  

PubMed Central

Background The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55–64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09–2.24), followed by effects on both stroke subtypes (1.66; 1.39–1.98 for hemorrhagic stroke and 1.63; 1.57–1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29–1.61) for IHD and 1.20 (1.15–1.25) for ischemic stroke. The RRs for 5 kg/m2 higher BMI for ages 55–64 ranged from 2.32 (2.04–2.63) for diabetes, to 1.44 (1.40–1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08–1.29) for IHD and 1.14 (1.01–1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group.

Farzadfar, Farshad; Stevens, Gretchen A.; Woodward, Mark; Wormser, David; Kaptoge, Stephen; Whitlock, Gary; Qiao, Qing; Lewington, Sarah; Di Angelantonio, Emanuele; vander Hoorn, Stephen; Lawes, Carlene M. M.; Ali, Mohammed K.; Mozaffarian, Dariush; Ezzati, Majid

2013-01-01

322

Analysis of leakage current mechanisms in Pt/Au Schottky contact on Ga-polarity GaN by Frenkel-Poole emission and deep level studies  

NASA Astrophysics Data System (ADS)

We report the Frenkel-Poole emission in Pt/Au Schottky contact on Ga-polarity GaN grown by molecular beam epitaxy using current-voltage-temperature (I-V-T) characteristics in the temperature ranging from 200 K to 375 K. Using thermionic emission model, the estimated Schottky barrier height is 0.49 eV at 200 K and 0.83 eV at 375 K, respectively, and it is observed that the barrier height increases with increase in temperature. The extracted emission barrier height (?t) for Ga-polarity GaN Schottky diode by Frenkel-Poole theory is about 0.15 eV. Deep level transient spectroscopy study shows a deep level with activation energy of 0.44 eV, having capture cross-section 6.09 × 10-14 cm2, which is located between the metal and semiconductor interface, and trap nature is most probably associated with dislocations in Ga-polarity GaN. The analysis of I-V-T characteristics represents that the leakage current is due to effects of electrical field and temperature on the emission of electron from a trap state near the metal-semiconductor interface into continuum states associated with conductive dislocations in Ga-polarity GaN Schottky diode.

Rao, Peta Koteswara; Park, Byungguon; Lee, Sang-Tae; Noh, Young-Kyun; Kim, Moon-Deock; Oh, Jae-Eung

2011-07-01

323

¹H NMR metabolomics analysis of the effect of dichloroacetate and allopurinol on breast cancers.  

PubMed

Metabolomics analysis was used to determine the effect of two well known, non-proprietary metabolic modulators, dichloroacetate and allopurinol on breast cancer cell lines. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor and allopurinol, a xanthine oxidase/dehydrogenase inhibitor, have been previously explored as chemotherapeutics showing potential in some cancer subtypes while at the same time leading to unexpected increase in proliferation in others. In this work, metabolic effects of these drugs, applied singly and in combination, were explored in three different breast cell lines including cancer cells, MDA-MB-231 and MCF-7 and normal control cell line, MCF-10A. The metabolic changes induced by these drugs were monitored by (1)H NMR metabolic profiling. Analyses were performed on complete spectral data as well as quantified metabolic data in intracellular fractions and extracellular media leading to the determination of the most significantly affected metabolites. The effect of dichloroacetate and allopurinol is the most apparent in the metabolic profile of extracellular media. In MCF-7 cells, dichloroacetate treatment is dominant with only a minor observed influence of allopurinol in combined treatment. In MDA-MB-231 cells, both allopurinol and DCA lead to a metabolic shift with the allopurinol change dominating the effect of combined treatment. Results show the power of metabolomics as a tool for fast molecular profiling of drug effects in cells. In summary, treatments of breast cancer cells with DCA and allopurinol result in larger changes in metabolites found in extracellular medium than intracellular pools. PMID:24074721

Lefort, Natalie; Brown, Amy; Lloyd, Vett; Ouellette, Rodney; Touaibia, Mohamed; Culf, Adrian S; Cuperlovic-Culf, Miroslava

2014-05-01

324

Analysis of Adult Neurogenesis: Evidence for a Prominent "Non-Neurogenic" DCX-Protein Pool in Rodent Brain  

PubMed Central

Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial “non-neurogenic” pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies.

Kremer, Thomas; Jagasia, Ravi; Herrmann, Annika; Matile, Hugues; Borroni, Edilio; Francis, Fiona; Kuhn, Hans Georg; Czech, Christian

2013-01-01

325

Prognostic Value of Perineural Invasion in Gastric Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Background The prognostic role of perineural invasion in gastric cancer is controversial. Here, we present a systemic review and meta-analysis of the association between perineural invasion and survival in resectable gastric cancer patients. Methods A comprehensive literature search for relevant reports published up to April 2013 was performed using PubMed, Embase, Web of Science and Wanfang Data. Studies that investigated the role of perineural invasion with a sample size greater than 100 were included and analyzed. Results A total of 30,590 gastric cancer patients who had undergone curative gastrectomy from twenty-four studies were included. The median rate of perineural invasion positive was 40.9% (6.8%–75.6%). Fourteen studies investigated overall survival unadjusted for other variables in 23,233 gastric cancer patients. The relative hazard estimates ranged from 0.568–7.901 with a combined random effects estimate of 2.261 (95% CI?=?1.841–2.777, P?=?0.000). The effect of perineural invasion on overall survival adjusted for other prognostic factors was reported in 17 studies incorporating 8,551 cases. The hazard estimates ranged from 0.420–8.110 with a pooled random effects estimates of 1.484 (95% CI?=?1.237–1.781, P?=?0.000). There was heterogeneity between the studies (Q?=?49.22, I-squared?=?67.5%, P?=?0.000). Disease-free survival was investigated adjusted in four studies incorporating 9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CI?=?1.230–1.527, P?=?0.000). Conclusion Perineural invasion is an independent prognostic factor affecting overall survival and disease-free survival of gastric cancer patients who had undergone the curative resection. This effect is independent of lymph node status, tumor size and the depth of invasion as well as a range of other biological variables on multivariate analysis. Large prospective studies are now needed to establish perineural invasion as an independent prognostic marker for gastric cancer.

Deng, Jing; You, Qihan; Gao, Yang; Yu, Qing; Zhao, Peng; Zheng, Yulong; Fang, Weijia; Xu, Nong; Teng, Lisong

2014-01-01

326

An Epidemiological Reappraisal of the Familial Aggregation of Prostate Cancer: A Meta-Analysis  

PubMed Central

Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25–2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37–4.15), and for those with affected father 2.35 times (CI:2.02–2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61–7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21–3.74), than in men aged 65 and older (RR:1.92, CI:1.49–2.47), p for interaction?=?0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6–63.5%) for men at all ages, 65.2% (CI:57.7–71.4%) for men younger than 65 and 47.9% (CI:37.1–56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4–85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65).

Kicinski, Michal; Vangronsveld, Jaco; Nawrot, Tim S.

2011-01-01

327

Genome-wide linkage analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses  

PubMed Central

Background Prostate cancer is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. Methods We performed a secondary analysis of 1233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. Results Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genomewide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive prostate cancer (PC) pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. Conclusions Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk prostate cancer pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify prostate cancer predisposition genes.

Christensen, G. Bryce; Baffoe-Bonnie, Agnes B.; George, Asha; Powell, Isaac; Bailey-Wilson, Joan E.; Carpten, John D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; English, Dallas R.; Foulkes, William D.; Maehle, Lovise; Moller, Pal; Eeles, Ros; Easton, Douglas; Badzioch, Michael D.; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Dimitrov, Latchezar; Xu, Jianfeng; Stanford, Janet L.; Johanneson, Bo; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Hebbring, Scott; Schaid, Daniel J.; Lange, Ethan M.; Cooney, Kathleen A.; Tammela, Teuvo L.J.; Schleutker, Johanna; Paiss, Thomas; Maier, Christiane; Gronberg, Henrik; Wiklund, Fredrik; Emanuelsson, Monica; Farnham, James M.; Cannon-Albright, Lisa A.; Camp, Nicola J.

2012-01-01

328

Swimming pool. View of aisle between swimming pool and seating ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Swimming pool. View of aisle between swimming pool and seating area. Non-original spa pool is partially visible on right. - Jewish Community Center of San Francisco, 3200 California Street, San Francisco, San Francisco County, CA

329

Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone: a posthoc pooled analysis of seven randomized controlled studies  

PubMed Central

Background The purpose of this study was to compare incidence rates and time course of extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) between oral and long-acting injectable (LAI) paliperidone. Methods The analysis included pooled data (safety analysis set, 2,256 antipsychotic-treated and 865 placebo-treated patients with schizophrenia) from seven randomized, double-blind, placebo-controlled paliperidone studies (three oral [6 weeks each] and four LAI [9–13 weeks]) and assessed comparable doses (oral, 3–15 mg; LAI, 25–150 mg eq. [US doses 39–234 mg]). We summarized incidence rates and time of onset for EPS-related TEAE, categorized by EPS group terms, ie, tremor, dystonia, hyperkinesia, parkinsonism, and dyskinesia, and use of anti-EPS medication. Mean scores over time for the Abnormal Involuntary Movement Scale (AIMS, for dyskinesia), Barnes Akathisia Rating Scale (BARS, for akathisia), and Simpson Angus Rating Scale (SAS, for parkinsonism) were graphed. Results Incidence rates for all categories of spontaneously reported EPS-related TEAEs except for hyperkinesia, were numerically lower in pooled LAI studies than in pooled oral studies. Highest rates were observed in the first week of paliperidone-LAI (for all EPS symptoms except dyskinesia) and oral paliperidone treatment (except parkinsonism and tremor). Anti-EPS medication use was significantly lower in LAI (12%) versus oral studies (17%, P = 0.0035). Mean values for EPS scale scores were similar between LAI and oral treatment at endpoint, and no dose response was evident. Mean reductions (standard deviation) from baseline to endpoint in EPS scale scores were larger for LAI (AIMS, ?0.10 [1.27]; BARS, ?0.09 [1.06]; SAS, ?0.04 [0.20]) versus oral studies (AIMS, ?0.08 [1.32]; BARS, ?0.03 [1.24]; SAS, 0.0 [0.23]). These changes favored LAI for BARS (P = 0.023) and SAS (P < 0.0001), but not for AIMS (P = 0.49), at endpoint for the studies. Conclusion In this posthoc descriptive analysis, incidence rates of spontaneously reported EPS-related TEAEs were numerically lower following approximately 90 days of exposure with LAI and approximately 40 days with oral paliperidone at comparable doses.

Gopal, Srihari; Liu, Yanning; Alphs, Larry; Savitz, Adam; Nuamah, Isaac; Hough, David

2013-01-01

330

Reference Values and Age and Sex Differences in Physical Performance Measures for Community-Dwelling Older Japanese: A Pooled Analysis of Six Cohort Studies  

PubMed Central

Objectives To determine age- and sex-specific reference values for six physical performance measures, i.e. hand-grip strength, one-legged stance, and gait speed and step length at both usual and maximum paces, and to investigate age and sex differences in these measures among community-dwelling older Japanese adults. Methods We conducted a pooled analysis of data from six cohort studies collected between 2002 and 2011 as part of the Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging. The pooled analysis included cross-sectional data from 4683 nondisabled, community-dwelling adults aged 65 years or older (2168 men, 2515 women; mean age: 74.0 years in men and 73.9 years in women). Results Unweighted simple mean (standard deviation) hand-grip strength, one-legged stance, usual gait speed, usual gait step length, maximum gait speed, and maximum gait step length were 31.7 (6.7) kg, 39.3 (23.0) s, 1.29 (0.25) m/s, 67.7 (10.0) cm, 1.94 (0.38) m/s, and 82.3 (11.6) cm, respectively, in men and 20.4 (5.0) kg, 36.8 (23.4) s, 1.25 (0.27) m/s, 60.8 (10.0) cm, 1.73 (0.36) m/s, and 69.7 (10.8) cm, respectively, in women. All physical performance measures showed significant decreasing trends with advancing age in both sexes (all P<0.001 for trend). We also constructed age- and sex-specific appraisal standards according to quintiles. With increasing age, the sex difference in hand-grip strength decreased significantly (P<0.001 for age and sex interaction). In contrast, sex differences significantly increased in all other measures (all P<0.05 for interactions) except step length at maximum pace. Conclusion Our pooled analysis yielded inclusive age- and sex-specific reference values and appraisal standards for major physical performance measures in nondisabled, community-dwelling, older Japanese adults. The characteristics of age-related decline in physical performance measures differed between sexes.

Seino, Satoshi; Shinkai, Shoji; Fujiwara, Yoshinori; Obuchi, Shuichi; Yoshida, Hideyo; Hirano, Hirohiko; Kim, Hun Kyung; Ishizaki, Tatsuro; Takahashi, Ryutaro

2014-01-01

331

Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis  

PubMed Central

Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC. Methods: Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity. Results: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95% CI 0.01 to 4). Conclusions: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.

Holty, J; Kuschner, W; Gould, M

2005-01-01

332

Telomerase Reverse Transcriptase Locus Polymorphisms and Cancer Risk: A Field Synopsis and Meta-Analysis  

PubMed Central

Background Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. Methods A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as “strong,” “moderate,” and “weak” according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. Results Eighty-five studies enrolling 490?901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. Conclusions To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans.

Verdi, Daunia; Pooley, Karen A.; Landi, Maria T.; Egan, Kathleen M.; Baird, Duncan M.; Prescott, Jennifer; De Vivo, Immaculata; Nitti, Donato

2012-01-01

333

Human Lung Cancer Risks from Radon - Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis  

PubMed Central

Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m?3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid.

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2012-01-01

334

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma in a pooled analysis of three studies  

PubMed Central

Background Elevated incidence of lymphoma has been observed among carriers of rare high-penetrance mutations in DNA repair genes (e.g., Nijmegen breakage syndrome, Ataxia-telangectasia syndrome, etc.). Common gene variants in DNA repair genes may also influence lymphomagenesis. Methods Study subjects were pooled from three population-based case-control studies of non-Hodgkin lymphoma (NHL) in the US and Australia. A total of 1,946 cases and 1,808 controls were analyzed. A total of 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions were genotyped. Unconditional logistic regression models were used to estimate the relative risk of NHL and NHL subtypes in relation to SNPs. Tail-strength statistics were used to test for the association between DNA repair pathways and NHL or NHL subtypes. The statistical significance of the smallest P-trend within each gene region was estimated by permutation-based resampling methods. Results Overall, DNA repair genetic polymorphisms were associated with NHL (P = 0.005). Tests for the double strand break repair (P = 0.02) and nucleotide excision repair (P = 0.04) pathways were also significant. Four gene regions were significantly associated with NHL or NHL subtypes at the 0.05 level: RAD50, BLM, RAD51/FAM82C, and ERCC3/MAP3K2. Specifically, BLM rs441399 (P trend = 0.004) and FAM82C rs2304583 (P trend = 0.001) were associated with follicular lymphoma, and XRCC4 rs13178127 was associated with NHL overall (P trend = 0.006) significantly. In addition, the ERCC3 rs4150506 was associated with reduced risk for marginal zone lymphoma (P trend = 0.002). Conclusion These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL.

Shen, Min; Menashe, Idan; Wang, Sophia S.; Zhang, Yawei; Armstrong, Bruce; Morton, Lindsay M.; Lan, Qing; Hartge, Patricia; Purdue, Mark P.; Cerhan, James R.; Grulich, Andrew; Cozen, Wendy; Yeager, Meredith; Holford, Theodore R.; Vajdic, Claire M.; Davis, Scott; Leaderer, Brian; Kricker, Anne; Schenk, Maryjean; Zahm, Shelia H.; Chatterjee, Nilanjan; Rothman, Nathaniel; Chanock, Stephen J.; Zheng, Tongzhang

2010-01-01

335

Association between NFKB1 -94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis  

PubMed Central

Nuclear factor-?B is associated with the pathogenesis of numerous malignancies, and the functional polymorphism ?94ins/del ATTG (rs28362491) in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the ?94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. We found that the NFKB1 promoter ?94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35). Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.

Tao, Jun; Cao, Qiang; Gu, Jinbao; Deng, Xiaheng; Wang, Jun; Liu, Xuzhong; Wang, Zijie; Wu, Bian; Lu, Qiang; Yin, Changjun

2014-01-01

336

Genetic Analysis for Stratification of Cancer Risk.  

National Technical Information Service (NTIS)

The present invention provides new methods for the assessment of cancer risk in the general population. These methods utilize particular alleles of two or more genes, in combination, to identify individuals with increased or decreased risk of cancer. Exem...

C. E. Aston D. Ralph E. Jupe

2004-01-01

337

Association between RASSF1A Promoter Methylation and Prostate Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Prostate cancer (PCa) remains as one of the most common cause of cancer related death among men in the US. The widely used prostate specific antigen (PSA) screening is limited by low specificity. The diagnostic value of other biomarkers such as RAS association domain family protein 1 A (RASSF1A) promoter methylation in prostate cancer and the relationship between RASSF1A methylation and pathological features or tumor stage remains to be established. Therefore, a meta-analysis of published studies was performed to understand the association between RASSF1A methylation and prostate cancer. In total, 16 studies involving 1431 cases and 565 controls were pooled with a random effect model in this investigation. The odds ratio (OR) of RASSF1A methylation in PCa case, compared to controls, was 14.73 with 95% CI = 7.58–28.61. Stratified analyses consistently showed a similar risk across different sample types and, methylation detection methods. In addition, RASSF1A methylation was associated with high Gleason score OR=2.35, 95% CI: 1.56–3.53. Furthermore, the pooled specificity for all included studies was 0.87 (95% CI: 0.72–0.94), and the pooled sensitivity was 0.76 (95% CI: 0.55–0.89). The specificity in each subgroup stratified by sample type remained above 0.84 and the sensitivity also remained above 0.60. These results suggested that RASSF1A promoter methylation would be a potential biomarker in PCa diagnosis and therapy.

Pan, Jincheng; Chen, Junxing; Zhang, Bo; Chen, Xu; Huang, Bin; Zhuang, Jintao; Mo, Chengqiang; Qiu, Shaopeng

2013-01-01

338

Vitamin D Supplementation and Breast Cancer Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials  

PubMed Central

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.

Maugeri-Sacca, Marcello; Stranges, Saverio; Santesso, Nancy; Mariani, Luciano; Giordano, Antonio; Sergi, Domenico; Pizzuti, Laura; Di Lauro, Luigi; Montella, Maurizio; Crispo, Anna; Barba, Maddalena

2013-01-01

339

Pooled analysis of adjunct extended-release quetiapine fumarate in patients with major depressive disorder according to ongoing SSRI or SNRI treatment.  

PubMed

This pooled analysis evaluated the efficacy of extended-release quetiapine fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups. PMID:24108148

Bauer, Michael; Demyttenaere, Koen; El-Khalili, Nizar; Thase, Michael E; Papakostas, George I; Szamosi, Johan; Earley, Willie R; Eriksson, Hans

2014-01-01

340

Weld pool phenomena  

SciTech Connect

During welding, the composition, structure and properties of the welded structure are affected by the interaction of the heat source with the metal. The interaction affects the fluid flow, heat transfer and mass transfer in the weld pool, and the solidification behavior of the weld metal. In recent years, there has been a growing recognition of the importance of the weld pool transport processes and the solid state transformation reactions in determining the composition, structure and properties of the welded structure. The relation between the weld pool transport processes and the composition and structure is reviewed. Recent applications of various solidification theories to welding are examined to understand the special problems of weld metal solidification. The discussion is focussed on the important problems and issues related to weld pool transport phenomena and solidification. Resolution of these problems would be an important step towards a science based control of composition, structure and properties of the weld metal.

David, S.A.; Vitek, J.M.; Zacharia, T. [Oak Ridge National Lab., TN (United States); DebRoy, T. [Pennsylvania State Univ., University Park, PA (United States)

1994-09-01

341

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis  

SciTech Connect

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2013-06-01

342

Blood ?-Tocopherol, ?-Tocopherol Levels and Risk of Prostate Cancer: A Meta-Analysis of Prospective Studies  

PubMed Central

Background Epidemiological studies that have examined the association of blood ?-tocopherol and ?-tocopherol (the principal bioactive form of vitamin E) levels with the risk of prostate cancer have yielded inconsistent results. In addition, a quantitative assessment of published studies is not available. Methods and Findings In this meta-analysis, relevant studies were sought by a search of the PubMed and Embase databases for articles published up to October 2013, with no restrictions. Bibliographies from retrieved articles also were scoured to find further eligible studies. Prospective studies that reported adjusted relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between blood tocopherol levels and the risk of prostate cancer were included. Nine nested case–control studies involving approximately 370,000 participants from several countries were eligible. The pooled RRs of prostate cancer for the highest versus lowest category of blood ?-tocopherol levels were 0.79 (95% CI: 0.68–0.91), and those for ?-tocopherol levels were 0.89 (95% CI: 0.71–1.12), respectively. Significant heterogeneity was present among the studies in terms of blood ?-tocopherol levels (p?=?0.008) but not in terms of blood ?-tocopherol levels (p?=?0.33). The risk of prostate cancer decreased by 21% for every 25-mg/L increase in blood ?-tocopherol levels (RR: 0.79; 95% CI: 0.69–0.91). Conclusions Blood ?-tocopherol levels, but not ?-tocopherol levels, were inversely associated with the risk of prostate cancer in this meta-analysis.

Xu, Qing

2014-01-01

343

What?s in the Pool? A Comprehensive Identification of Disinfection By-Products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water  

EPA Science Inventory

Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in pool water and related those DBPs to the mutagenicity of pool wate...